Omega 3: Why is it that bendy is trendy?

[Durand]

Hi,

Why is it that Omega 3 fats makes good cholesterol? From what
I've read about its chemistry, it shouldn't. Could you read
the assumptions I've made, and see where my logic is wrong?

1) OMEGA 3 IS BENDY: Omega 3 fats are called Omega 3 because
they have a double join in their carbon chain every three
carbon atoms. Due to the electrical properties of atoms,
this makes the chain bend every three atoms. So if you
looked at one under a super-powerful microscope, Omega 3
fat molecules looks like a W. In contrast, normal saturated
fats don't have any double bonds, so they are straight like
a stick --- .

2) OMEGA 3 IS LIQUID: If you imagine a whole bunch of straight
sticks in a box, they pack down nicely, so you can fit more
in to a given area. In the same way, saturated fats pack
down nice and tight because the molecules are straight, so
you end up with a solid, like butter or animal fat. On the
other hand, Omega 3 is all bendy, so is hopeless at packing
down tight. Therefore, they take up more room, and you get
less molecules for the same amount of space. That's why
Omega 3 fats end up as liquids.

3) GOOD CHOLESTEROL IS DENSE: Omega 3 acids make "good
cholesterol". One reason your body makes cholesterol in the
first place is because to patch up dents in your arteries,
caused by blood flow wearing away the insides. "Good
cholesterol" is considered good because it is tightly
packed, and solid, and therefore fills the gap like putty.
On the other hand "bad cholesterol" is big and fluffy, not
at all dense, and doesn't patch the holes up properly.
What's more, it tends to get washed off the hole later on,
and sits around in the blood stream forming clots.

AND YET - they say that polyunsaturated fats like Omega 3
makes the good, dense cholesterol, while saturated fats make
the bad fluffy cholesterol. How can it when it's so
hopelessly bendy?

[monty1945]

What happens is that LDL gets oxidized (because there is so
much unstable PUFAs in it), macrophages attack these "foreign"
molecules, and at a certain point, the macrophages become
dysfunctional, and end up stuck in arteries. They "spill their
guts," causing inflammation and fibrotic changes. On my free
site, there is a study cited which found that arterial plaques
had more PUFAs than SFAs. There are many other relevant
studies cited there as well:

http://groups.msn.com/TheScientificDebateForum-

"I also just found this:Glycated Hemoglobin Level Is Strongly
Related to the Prevalence of Carotid Artery Plaques With High
Echogenicity in Nondiabetic Individuals."

Source: Circulation. 2004;110:466-470.

This is important because arachidonic acid has been found to
be an incredibly potent glycating agent (study cited on my
site), and if you have a very low PUFA diet, you won't have
arachidonic acid in your body (if you already do, it will take
up to 2 years to get it out of your body).

[Taka]

The establishment is going to put Omega-3 in our food like it
or not :- (

Poult Sci. 2000 Jul;79(7):961-70.

Human requirement for N-3 polyunsaturated fatty acids.

Simopoulos AP. The Center for Genetics Nutrition and Health,
Washington, DC 20009, USA.

The diet of our ancestors was less dense in calories, being
higher in fiber, rich in fruits, vegetables, lean meat, and
fish. As a result, the diet was lower in total fat and
saturated fat, but contained equal amounts of n-6 and n-3
essential fatty acids. Linoleic acid (LA) is the major n-6
fatty acid, and alpha-linolenic acid (ALA) is the major n-3
fatty acid. In the body, LA is metabolized to arachidonic
acid (AA), and ALA is metabolized to eicosapentaenoic acid
(EPA) and docosahexaenoic acid (DHA). The ratio of n-6 to n-3
essential fatty acids was 1 to 2:1 with higher levels of the
longer-chain polyunsaturated fatty acids (PUFA), such as EPA,
DHA, and AA, than today's diet. Today this ratio is about 10
to 1:20 to 25 to 1, indicating that Western diets are
deficient in n-3 fatty acids compared with the diet on which
humans evolved and their genetic patterns were established.
The n-3 and n-6 EPA are not interconvertible in the human
body and are important components of practically all cell
membranes. The N-6 and n-3 fatty acids influence eicosanoid
metabolism, gene expression, and intercellular cell-to-cell
communication. The PUFA composition of cell membranes is, to
a great extent, dependent on dietary intake. Therefore,
appropriate amounts of dietary n-6 and n-3 fatty acids need
to be considered in making dietary recommendations. These two
classes of PUFA should be distinguished because they are
metabolically and functionally distinct and have opposing
physiological functions; their balance is important for
homeostasis and normal development. Studies with nonhuman
primates and human newborns indicate that DHA is essential
for the normal functional development of the retina and
brain, particularly in premature infants. A balanced n-6/n-3
ratio in the diet is essential for normal growth and
development and should lead to decreases in cardiovascular
disease and other chronic diseases and improve mental health.
Although a recommended dietary allowance for essential fatty
acids does not exist, an adequate intake (AI) has been
estimated for n-6 and n-3 essential fatty acids by an
international scientific working group. For Western
societies, it will be necessary to decrease the intake of n-6
fatty acids and increase the intake of n-3 fatty acids. The
food industry is already taking steps to return n-3 essential
fatty acids to the food supply by enriching various foods
with n-3 fatty acids. To obtain the recommended AI, it will
be necessary to consider the issues involved in enriching the
food supply with n-3 PUFA in terms of dosage, safety, and
sources of n-3 fatty acids. PMID: 10901194

[Noname]

In article <016bd246-191f-4b9c-b496-efcaa2dccfff@k39g2000hsf.-
googlegroups.com>, Durand <durand.sinclair@gmail.com> wrote:

> Hi,
>
> Why is it that Omega 3 fats makes good cholesterol? From
> what I've read about its chemistry, it shouldn't. Could
> you read the assumptions I've made, and see where my logic
> is wrong?
>
> 1) OMEGA 3 IS BENDY: Omega 3 fats are called Omega 3 because
> they have a double join in their carbon chain every three
> carbon atoms. Due to the electrical properties of atoms,
> this makes the chain bend every three atoms. So if you
> looked at one under a super-powerful microscope, Omega 3
> fat molecules looks like a W. In contrast, normal
> saturated fats don't have any double bonds, so they are
> straight like a stick --- .
>
> 2) OMEGA 3 IS LIQUID: If you imagine a whole bunch of
> straight sticks in a box, they pack down nicely, so you
> can fit more in to a given area. In the same way,
> saturated fats pack down nice and tight because the
> molecules are straight, so you end up with a solid, like
> butter or animal fat. On the other hand, Omega 3 is all
> bendy, so is hopeless at packing down tight. Therefore,
> they take up more room, and you get less molecules for
> the same amount of space. That's why Omega 3 fats end up
> as liquids.
>
> 3) GOOD CHOLESTEROL IS DENSE: Omega 3 acids make "good
> cholesterol". One reason your body makes cholesterol in
> the first place is because to patch up dents in your
> arteries, caused by blood flow wearing away the insides.
> "Good cholesterol" is considered good because it is
> tightly packed, and solid, and therefore fills the gap
> like putty. On the other hand "bad cholesterol" is big
> and fluffy, not at all dense, and doesn't patch the holes
> up properly. What's more, it tends to get washed off the
> hole later on, and sits around in the blood stream
> forming clots.
>
> AND YET - they say that polyunsaturated fats like Omega 3
> makes the good, dense cholesterol, while saturated fats make
> the bad fluffy cholesterol. How can it when it's so
> hopelessly bendy?

Maybe it's not so direct, and instead is because it
increases membrane fluidity which makes every cell in your
body work better.

[Mattlb]

On Jan 30, 10:03 pm, monty1...@lycos.com wrote:
> What happens is that LDL gets oxidized (because there is so
> much unstable PUFAs in it),

Mead acid being just such a PUFA of course.

> macrophages attack these "foreign" molecules, and at a
> certain point, the macrophages become dysfunctional, and end
> up stuck in arteries.

Your vague handwaving suggests you don't understand the
sequence of events here. The LDL oxidation occurs in the
artery wall, then macrophages invade the artery wall and then
they take up the oxLDL.

> "I also just found this:Glycated Hemoglobin Level Is
> Strongly Related to the Prevalence of Carotid Artery Plaques
> With High Echogenicity in Nondiabetic Individuals."
>
> Source: Circulation. 2004;110:466-470.
>
> This is important because arachidonic acid has been found to
> be an incredibly potent glycating agent

That would be a good trick since glycation is the
non-enzymatic addition of sugars to other molecules,
principally proteins. Do you think arachidonic acid is a sugar
now, or is "glycating agent" just another example of you
misusing/misunderstanding terms?

MattLB

[Mattlb]

On Jan 30, 9:43 pm, Durand <durand.sincl...@gmail.com> wrote:
> Hi,
>
> Why is it that Omega 3 fats makes good cholesterol? From
> what I've read about its chemistry, it shouldn't. Could
> you read the assumptions I've made, and see where my logic
> is wrong?
>
> 3) GOOD CHOLESTEROL IS DENSE: Omega 3 acids make "good
> cholesterol". One reason your body makes cholesterol in
> the first place is because to patch up dents in your
> arteries, caused by blood flow wearing away the insides.
> "Good cholesterol" is considered good because it is
> tightly packed, and solid, and therefore fills the gap
> like putty. On the other hand "bad cholesterol" is big
> and fluffy, not at all dense, and doesn't patch the holes
> up properly. What's more, it tends to get washed off the
> hole later on, and sits around in the blood stream
> forming clots.

I think part of the problem here is the use of the terms good
and bad cholesterol. What they actually refer to is two types
of lipoprotein in the blood.

Low density lipoprotein (LDL) is called "bad cholesterol"
because it is richer in cholesterol than the other lipids it
carries and is the one that ends up lodged in artery walls
(which is bad).

High density lipoprotein (HDL) is mostly protein with actually
quite a small amount of cholesterol. It is called "good
cholesterol" because it picks up cholesterol from around the
body and delivers it to the liver.

The terms good and bad cholesterol therefore don't refer
to cholesterol molecules made from different fatty acids,
they refer to different proteins that carry cholesterol
around the body.

The density issue is a tricky one too, as although HDL is
more dense than LDL it's not significant that it is. What
*is* signficant is that some people have what's called an
LDL-B phenotype where they make LDL that's smaller and denser
than normal and enters the artery wall 40-50% faster than
normal LDL. Smaller LDL particles are also more easily
oxidised. When it comes to lipoproteins, bigger and fluffier
is actually better.

MattLB

[Taka]

On Jan 31, 1:02 pm, noname <nos...@aol.com> wrote:
> In article <016bd246-191f-4b9c-b496-efcaa2dcc...@k39g2000hs-
> f.googlegroups.com>,
>
>
>
> Durand <durand.sincl...@gmail.com> wrote:
> > Hi,
>
> > Why is it that Omega 3 fats makes good cholesterol? From
> > what I've read about its chemistry, it shouldn't. Could
> > you read the assumptions I've made, and see where my logic
> > is wrong?
>
> > 1) OMEGA 3 IS BENDY: Omega 3 fats are called Omega 3
> > because they have a double join in their carbon chain
> > every three carbon atoms. Due to the electrical
> > properties of atoms, this makes the chain bend every
> > three atoms. So if you looked at one under a
> > super-powerful microscope, Omega 3 fat molecules looks
> > like a W. In contrast, normal saturated fats don't
> > have any double bonds, so they are straight like a
> > stick --- .
>
> > 2) OMEGA 3 IS LIQUID: If you imagine a whole bunch of
> > straight sticks in a box, they pack down nicely, so you
> > can fit more in to a given area. In the same way,
> > saturated fats pack down nice and tight because the
> > molecules are straight, so you end up with a solid,
> > like butter or animal fat. On the other hand, Omega 3
> > is all bendy, so is hopeless at packing down tight.
> > Therefore, they take up more room, and you get less
> > molecules for the same amount of space. That's why
> > Omega 3 fats end up as liquids.
>
> > 3) GOOD CHOLESTEROL IS DENSE: Omega 3 acids make "good
> > cholesterol". One reason your body makes cholesterol in
> > the first place is because to patch up dents in your
> > arteries, caused by blood flow wearing away the
> > insides. "Good cholesterol" is considered good because
> > it is tightly packed, and solid, and therefore fills
> > the gap like putty. On the other hand "bad cholesterol"
> > is big and fluffy, not at all dense, and doesn't patch
> > the holes up properly. What's more, it tends to get
> > washed off the hole later on, and sits around in the
> > blood stream forming clots.
>
> > AND YET - they say that polyunsaturated fats like Omega 3
> > makes the good, dense cholesterol, while saturated fats
> > make the bad fluffy cholesterol. How can it when it's so
> > hopelessly bendy?
>
> Maybe it's not so direct, and instead is because it
> increases membrane fluidity which makes every cell in your
> body work better.

You may need that increased fluidity in things like sperm
tails or neuron dendrites or peripheral body parts and skin if
you live in a cold climate.

Taka

[Taka]

On Jan 31, 11:55 pm, MattLB <mat...@angelfire.com> wrote:
> On Jan 30, 10:03 pm, monty1...@lycos.com wrote:
>
> > What happens is that LDL gets oxidized (because there is
> > so much unstable PUFAs in it),
>
> Mead acid being just such a PUFA of course.

If you understood biochemistry you would notice that it's
quite different than the n-3 and n-6 series especially in
respect to stability.

> > macrophages attack these "foreign" molecules, and at a
> > certain point, the macrophages become dysfunctional, and
> > end up stuck in arteries.
>
> Your vague handwaving suggests you don't understand the
> sequence of events here. The LDL oxidation occurs in the
> artery wall, then macrophages invade the artery wall and
> then they take up the oxLDL.
>
> > "I also just found this:Glycated Hemoglobin Level Is
> > Strongly Related to the Prevalence of Carotid Artery
> > Plaques With High Echogenicity in Nondiabetic
> > Individuals."
>
> > Source: Circulation. 2004;110:466-470.
>
> > This is important because arachidonic acid has been found
> > to be an incredibly potent glycating agent
>
> That would be a good trick since glycation is the
> non-enzymatic addition of sugars to other molecules,
> principally proteins.

with the exception that it is mediated by the oxidized PUFAs
...

Taka

> Do you think arachidonic acid is a sugar now, or is
> "glycating agent" just another example of you
> misusing/misunderstanding terms?
>
> MattLB

[Taka]

On Feb 1, 12:17 am, MattLB <mat...@angelfire.com> wrote:
> Low density lipoprotein (LDL) is called "bad cholesterol"
> because it is richer in cholesterol than the other lipids it
> carries and is the one that ends up lodged in artery walls
> (which is bad).

How bad if you need to plug an arterial hole? Without the
liver making VitC for collagen synthesis this may save
your life ...

Taka

[Durand]

On Feb 1, 2:17=A0am, MattLB <mat...@angelfire.com> wrote:
> On Jan 30, 9:43 pm, Durand <durand.sincl...@gmail.com>
> wrote:
>
> > Hi,
>
> > Why is it that Omega 3 fats makes good cholesterol? From
> > what I've read about its chemistry, it shouldn't. Could
> > you read the assumptions I've made, and see where my logic
> > is wrong?
>
> > 3) GOOD CHOLESTEROL IS DENSE: Omega 3 acids make "good
> > cholesterol". One reason your body makes cholesterol in
> > the first place is because to patch up dents in your
> > arteries, caused by blood flow wearing away the
> > insides. "Good cholesterol" is considered good because
> > it is tightly packed, and solid, and therefore fills
> > the gap like putty. On the other hand "bad cholesterol"
> > is big and fluffy, not at all dense, and doesn't patch
> > the holes up properly. What's more, it tends to get
> > washed off the hole later on, and sits around in the
> > blood stream forming clots.
>
> I think part of the problem here is the use of the terms
> good and bad cholesterol. What they actually refer to is two
> types of lipoprotein in the blood.
>
> Low density lipoprotein (LDL) is called "bad cholesterol"
> because it is richer in cholesterol than the other lipids it
> carries and is the one that ends up lodged in artery walls
> (which is bad).
>
> High density lipoprotein (HDL) is mostly protein with
> actually quite a small amount of cholesterol. It is called
> "good cholesterol" because it picks up cholesterol from
> around the body and delivers it to the liver.
>
> The terms good and bad cholesterol therefore don't refer to
> cholesterol molecules made from different fatty acids, they
> refer to different proteins that carry cholesterol around
> the body.
>
> The density issue is a tricky one too, as although HDL is
> more dense than LDL it's not significant that it is. What
> *is* signficant is that some people have what's called an
> LDL-B phenotype where they make LDL that's smaller and
> denser than normal and enters the artery wall 40-50% faster
> than normal LDL. Smaller LDL particles are also more easily
> oxidised. When it comes to lipoproteins, bigger and fluffier
> is actually better.
>
> MattLB

That's a great answer, Matt. I thought cholesterol was a fat,
rather than a lipid trucked around by a protein. Thanks for
clearing that up

[Mattlb]

On Feb 1, 12:28 pm, Durand <durand.sincl...@gmail.com> wrote:
> On Feb 1, 2:17 am, MattLB <mat...@angelfire.com> wrote:
>
>
>
> > On Jan 30, 9:43 pm, Durand <durand.sincl...@gmail.com>
> > wrote:
>
> > > Hi,
>
> > > Why is it that Omega 3 fats makes good cholesterol? From
> > > what I've read about its chemistry, it shouldn't. Could
> > > you read the assumptions I've made, and see where my
> > > logic is wrong?
>
> > > 3) GOOD CHOLESTEROL IS DENSE: Omega 3 acids make "good
> > > cholesterol". One reason your body makes cholesterol
> > > in the first place is because to patch up dents in
> > > your arteries, caused by blood flow wearing away the
> > > insides. "Good cholesterol" is considered good
> > > because it is tightly packed, and solid, and
> > > therefore fills the gap like putty. On the other hand
> > > "bad cholesterol" is big and fluffy, not at all
> > > dense, and doesn't patch the holes up properly.
> > > What's more, it tends to get washed off the hole
> > > later on, and sits around in the blood stream forming
> > > clots.
>
> > I think part of the problem here is the use of the terms
> > good and bad cholesterol. What they actually refer to is
> > two types of lipoprotein in the blood.
>
> > Low density lipoprotein (LDL) is called "bad cholesterol"
> > because it is richer in cholesterol than the other lipids
> > it carries and is the one that ends up lodged in artery
> > walls (which is bad).
>
> > High density lipoprotein (HDL) is mostly protein with
> > actually quite a small amount of cholesterol. It is called
> > "good cholesterol" because it picks up cholesterol from
> > around the body and delivers it to the liver.
>
> > The terms good and bad cholesterol therefore don't refer
> > to cholesterol molecules made from different fatty acids,
> > they refer to different proteins that carry cholesterol
> > around the body.
>
> > The density issue is a tricky one too, as although HDL is
> > more dense than LDL it's not significant that it is. What
> > *is* signficant is that some people have what's called an
> > LDL-B phenotype where they make LDL that's smaller and
> > denser than normal and enters the artery wall 40-50%
> > faster than normal LDL. Smaller LDL particles are also
> > more easily oxidised. When it comes to lipoproteins,
> > bigger and fluffier is actually better.
>
> > MattLB
>
> That's a great answer, Matt. I thought cholesterol was a
> fat, rather than a lipid trucked around by a protein. Thanks
> for clearing that up

Lipid is just an umbrella term that covers fats, oils and some
other hydrophobic molecules. Cholesterol *is* a fat in the
general sense, but a very different sort of fat to the type
containing fatty acids.

MattLB

[Mattlb]

On Feb 1, 6:34 am, Taka <taka0...@gmail.com> wrote:
> On Feb 1, 12:17 am, MattLB <mat...@angelfire.com> wrote:
>
> > Low density lipoprotein (LDL) is called "bad cholesterol"
> > because it is richer in cholesterol than the other lipids
> > it carries and is the one that ends up lodged in artery
> > walls (which is bad).
>
> How bad if you need to plug an arterial hole?

That's what platelets are for.

Also LDL lodged in the artery is underneath the
epithelium, which may be physically intact, rather than
just plugging a hole.

MattLB

[Mattlb]

On Feb 1, 6:29 am, Taka <taka0...@gmail.com> wrote:
> On Jan 31, 11:55 pm, MattLB <mat...@angelfire.com> wrote:
>
> > On Jan 30, 10:03 pm, monty1...@lycos.com wrote:
>
> > > What happens is that LDL gets oxidized (because there is
> > > so much unstable PUFAs in it),
>
> > Mead acid being just such a PUFA of course.
>
> If you understood biochemistry you would notice that it's
> quite different than the n-3 and n-6 series especially in
> respect to stability.

Are you claiming that Mead acid can't be deleteriously
oxidised in the body? If so, why not? Just saying "It's more
stable" is too vague.

> > > This is important because arachidonic acid has been
> > > found to be an incredibly potent glycating agent
>
> > That would be a good trick since glycation is the
> > non-enzymatic addition of sugars to other molecules,
> > principally proteins.
>
> with the exception that it is mediated by the oxidized
> PUFAs ...

Glycation doesn't require PUFA oxidation. PUFA free
radicalisation can modify proteins in a similar way to
the endproducts of glycation, but you can't glycate
without a sugar.

MattLB

[Taka]

On Feb 1, 11:24 pm, MattLB <mat...@angelfire.com> wrote:

> > > Mead acid being just such a PUFA of course.
>
> > If you understood biochemistry you would notice that it's
> > quite different than the n-3 and n-6 series especially in
> > respect to stability.
>
> Are you claiming that Mead acid can't be deleteriously
> oxidised in the body? If so, why not? Just saying "It's more
> stable" is too vague.

You have short memory MattLB. I am not going to repeat this
more than twice or make a site like Monty to refer to each
time you ask the same question:

In the thread entitled "Can Mead acid substitute for EFAs
or should they be promoted to the status of vitamins?" it
was written:

On Nov 9, 11:57 pm, MattLB <mat...@angelfire.com> wrote:
> It's not simply incorporation into LDL, it's esterification
> of the FA to cholesterol. It would be interesting for you to
> now be pushing the increased number of double bonds in Mead
> acid as making it better than LA, where before you were
> claiming the fewer number of double bonds made it better
> than AA/EPA.

LA = 2 double bonds Mead acid = 3 double bonds AA = 4 double
bonds (!) EPA = 5 double bonds (!!) DHA = 6 double bonds (!!!)

Moreover, EPA/DHA have the last double bond only 2 C atoms
from the end what makes them even more reactive (in AA it's
"shielded" with 5 C atoms, in Mead acid it's even 8 C atoms
from the end!). Have a look at
http://www.lipomics.com/fatty_acids/

So Mead acid scores better than AA and may have even
comparable stability to LA given that in LA the last double
bond is 5 C atoms from the end. The distance of double bonds
from the end has been discussed in papers suggesting that DHA
in membranes shortens lifespan.

Taka

[Ron Peters]

On Jan 30, 3:43=A0pm, Durand <durand.sincl...@gmail.com>
wrote:

> Why is it that Omega 3 fats makes good cholesterol? From
> what I've read about its chemistry, it shouldn't. Could
> you read the assumptions I've made, and see where my logic
> is wrong?

> 1) OMEGA 3 IS BENDY: Omega 3 fats are called Omega 3 because
> they have a double join in their carbon chain every three
> carbon atoms. Due to the electrical properties of atoms,
> this makes the chain bend every three atoms. So if you
> looked at one under a super-powerful microscope, Omega 3
> fat molecules looks like a W. In contrast, normal
> saturated fats don't have any double bonds, so they are
> straight like a stick --- .

That's correct.

> 2) OMEGA 3 IS LIQUID: If you imagine a whole bunch of
> straight sticks in a box, they pack down nicely, so you
> can fit more in to a given area. In the same way,
> saturated fats pack down nice and tight because the
> molecules are straight, so you end up with a solid, like
> butter or animal fat. On the other hand, Omega 3 is all
> bendy, so is hopeless at packing down tight. Therefore,
> they take up more room, and you get less molecules for
> the same amount of space. That's why Omega 3 fats end up
> as liquids.

Yes, the melting point of triglycerides consisting of mainly
omega 3 and omega 6 fatty acids is lower than that for
monounsaturated and saturated fats.

> 3) GOOD CHOLESTEROL IS DENSE: Omega 3 acids make "good
> cholesterol". One reason your body makes cholesterol in
> the first place is because to patch up dents in your
> arteries, caused by blood flow wearing away the insides.
> "Good cholesterol" is considered good because it is
> tightly packed, and solid, and therefore fills the gap
> like putty. On the other hand "bad cholesterol" is big
> and fluffy, not at all dense, and doesn't patch the holes
> up properly. What's more, it tends to get washed off the
> hole later on, and sits around in the blood stream
> forming clots.

AFIK, that's not the mechanism for atherosclerosis.

> AND YET - they say that polyunsaturated fats like Omega 3
> makes the good, dense cholesterol, while saturated fats make
> the bad fluffy cholesterol. How can it when it's so
> hopelessly bendy?

Omega 3 fatty acid is not the main fatty acid in HDL,
nervonic acid
is. Palmitic acid is the main fatty acid for LDL.

--
Ron

[Durand]

On Feb 4, 4:45=A0pm, Ron Peterson <r...@shell.core.com> wrote:
> On Jan 30, 3:43=A0pm, Durand
> <durand.sincl...@gmail.com> wrote:
>
> > Why is it that Omega 3 fats makes good cholesterol? From
> > what I've read about its chemistry, it shouldn't. Could
> > you read the assumptions I've made, and see where my logic
> > is wrong?
> > 1) OMEGA 3 IS BENDY: Omega 3 fats are called Omega 3
> > because they have a double join in their carbon chain
> > every three carbon atoms. Due to the electrical
> > properties of atoms, this makes the chain bend every
> > three atoms. So if you looked at one under a
> > super-powerful microscope, Omega 3 fat molecules looks
> > like a W. In contrast, normal saturated fats don't
> > have any double bonds, so they are straight like a
> > stick --- .
>
> That's correct.
>
> > 2) OMEGA 3 IS LIQUID: If you imagine a whole bunch of
> > straight sticks in a box, they pack down nicely, so you
> > can fit more in to a given area. In the same way,
> > saturated fats pack down nice and tight because the
> > molecules are straight, so you end up with a solid,
> > like butter or animal fat. On the other hand, Omega 3
> > is all bendy, so is hopeless at packing down tight.
> > Therefore, they take up more room, and you get less
> > molecules for the same amount of space. That's why
> > Omega 3 fats end up as liquids.
>
> Yes, the melting point of triglycerides consisting of mainly
> omega 3 and omega 6 fatty acids is lower than that for
> monounsaturated and saturated fats.
>
> > 3) GOOD CHOLESTEROL IS DENSE: Omega 3 acids make "good
> > cholesterol". One reason your body makes cholesterol in
> > the first place is because to patch up dents in your
> > arteries, caused by blood flow wearing away the
> > insides. "Good cholesterol" is considered good because
> > it is tightly packed, and solid, and therefore fills
> > the gap like putty. On the other hand "bad cholesterol"
> > is big and fluffy, not at all dense, and doesn't patch
> > the holes up properly. What's more, it tends to get
> > washed off the hole later on, and sits around in the
> > blood stream forming clots.
>
> AFIK, that's not the mechanism for atherosclerosis.
>
> > AND YET - they say that polyunsaturated fats like Omega 3
> > makes the good, dense cholesterol, while saturated fats
> > make the bad fluffy cholesterol. How can it when it's so
> > hopelessly bendy?
>
> Omega 3 fatty acid is not the main fatty acid in HDL,
> nervonic acid
> is. =A0Palmitic acid is the main fatty acid for LDL.
>
> --
> =A0 =A0Ron

Thanks for going through each point so thoroughly Ron.

But if Omega 3 fatty acids is not so important in HDL, and
I've misunderstood its mechanism in the body, what's so good
about Omega 3s that it's recommended all over the place?

Thanks

Durand

[Mattlb]

On Feb 1, 4:26 pm, Taka <taka0...@gmail.com> wrote:
> On Feb 1, 11:24 pm, MattLB <mat...@angelfire.com> wrote:
> > > If you understood biochemistry you would notice that
> > > it's quite different than the n-3 and n-6 series
> > > especially in respect to stability.
>
> > Are you claiming that Mead acid can't be deleteriously
> > oxidised in the body? If so, why not? Just saying "It's
> > more stable" is too vague.
>
> You have short memory MattLB.

It seems you have too, as you've answered a different question
to the one I asked.

> So Mead acid scores better than AA and may have even
> comparable stability to LA given that in LA the last double
> bond is 5 C atoms from the end. The distance of double bonds
> from the end has been discussed in papers suggesting that
> DHA in membranes shortens lifespan.

I think you need to read http://www.ncbi.nlm.nih.gov/pubmed/1-
7156083?ordinalpos=4&itool=EntrezSystem2.PEntrez.Pubmed.Pubme-
d_ResultsPanel.Pubmed_RVDocSum

which states there's no correlation between number of double
bonds and lifespan, nor DHA content and lifespan.

MattLB

[Ron Peters]

On Feb 4, 12:58=A0am, Durand <durand.sincl...@gmail.com>
wrote:

> But if Omega 3 fatty acids is not so important in HDL, and
> I've misunderstood its mechanism in the body, what's so good
> about Omega 3s that it's recommended all over the place?

http://circ.ahajournals.org/cgi/content/full/106/21/2747
posits a number of possible explanations of how omega 3
works, but there have been some additional explanations
since the paper was published such as the anti-arrhythmic
action of omega 3.

The above paper claims that oxidation of omega 3 isn't fully
understood in vivo as to whether it's harmful.

--
Ron

[Taka]

On Feb 4, 10:37 pm, MattLB <mat...@angelfire.com> wrote:
> On Feb 1, 4:26 pm, Taka <taka0...@gmail.com> wrote:
>
> > On Feb 1, 11:24 pm, MattLB <mat...@angelfire.com> wrote:
> > > > If you understood biochemistry you would notice that
> > > > it's quite different than the n-3 and n-6 series
> > > > especially in respect to stability.
>
> > > Are you claiming that Mead acid can't be deleteriously
> > > oxidised in the body? If so, why not? Just saying "It's
> > > more stable" is too vague.
>
> > You have short memory MattLB.
>
> It seems you have too, as you've answered a different
> question to the one I asked.

Yes, I agree that anything except saturated fatty acid can be
"deleteriously oxidised in the body" but the question is how
fast and how bad! Have you ever heard about something called
the iodine number?

> > So Mead acid scores better than AA and may have even
> > comparable stability to LA given that in LA the last
> > double bond is 5 C atoms from the end. The distance of
> > double bonds from the end has been discussed in papers
> > suggesting that DHA in membranes shortens lifespan.
>
> I think you need to readhttp://www.ncbi.nlm.nih.gov/pubmed/-
> 17156083?ordinalpos=4&itool=Entrez...
>
> which states there's no correlation between number of double
> bonds and lifespan, nor DHA content and lifespan.

You are obsessed with that particular single paper like people
are with the nurse study ... Too bad I don't have access to
the full text but it seems to be just another "statistical
play" and they are embarrassing themselves even in the
Abstract by giving it a title "N-3 polyunsaturated fatty acids
impair lifespan" if they want to contradict the membrane
pacemaker theory of aging.

Taka

[Mark Thors]

Ron Peterson wrote:
>
> On Jan 30, 3:43 pm, Durand <durand.sincl...@gmail.com>
> wrote:
>
> > 3) GOOD CHOLESTEROL IS DENSE: Omega 3 acids make "good
> > cholesterol". One reason your body makes cholesterol in
> > the first place is because to patch up dents in your
> > arteries, caused by blood flow wearing away the
> > insides. "Good cholesterol" is considered good because
> > it is tightly packed, and solid, and therefore fills
> > the gap like putty. On the other hand "bad cholesterol"
> > is big and fluffy, not at all dense, and doesn't patch
> > the holes up properly. What's more, it tends to get
> > washed off the hole later on, and sits around in the
> > blood stream forming clots.
>
> AFIK, that's not the mechanism for atherosclerosis.

It's not even close. The velocity of blood flow right at the
surface of the arteries is zero. That's because of the
boundary layer effect. Cholesterol doesn't get "washed away".

A similar phenomenon occurs in water pipes. Pipe scale
(mineral deposit) builds up in pipes, rather than getting
"washed away", again because there is a stationary boundary
layer on the inner surface of the pipe.

[Mattlb]

On Feb 5, 1:16 am, Taka <taka0...@gmail.com> wrote:
> On Feb 4, 10:37 pm, MattLB <mat...@angelfire.com> wrote:
> > It seems you have too, as you've answered a different
> > question to the one I asked.
>
> Yes, I agree that anything except saturated fatty acid can
> be "deleteriously oxidised in the body" but the question is
> how fast and how bad!

In the escalating conditions of an atheroma it makes very
little difference which fatty acid is present - they're all
being exposed to highly oxidising conditions.

> Have you ever heard about something called the iodine
> number?

Addition reactions have nothing to do with the hydrogen
abstraction processes involved in lipid peroxidation. The
iodine reaction is done with an excess to ensure all the
double bonds are converted to give a count. Nothing to do with
stability in vivo.

> > I think you need to read http://www.ncbi.nlm.nih.gov/pubm-
> > ed/17156083?ordinalpos=4&itool=Entrez...
>
> > which states there's no correlation between number of
> > double bonds and lifespan, nor DHA content and lifespan.
>
> You are obsessed with that particular single paper

First time I've seen or mentioned it.

> Too bad I don't have access to the full text but it seems to
> be just another "statistical play"

They did the study precisely because others had statistical
flaws. I've tagged on the introduction from the paper below.

> embarrassing themselves even in the Abstract by giving it
> a title "N-3 polyunsaturated fatty acids impair lifespan"
> if they want to contradict the membrane pacemaker theory
> of aging.

The title is a strange choice, but refers to an imbalance
between omega 3 and 6 being correlated with reduced lifespan.
DHA content alone has no relationship with lifespan, nor do
any other PUFA.

MattLB

Introduction

Polyunsaturated fatty acids (PUFA) are essential components of
dietary fats and have a number of important cellular functions
including regulation of enzymes, ion pumps, and immune
responses (Stubbs & Smith, 1984; Pond & Mattacks, 1998). In
the context of aging, however, there are several arguments
suggesting that PUFAs may adversely affect maximum lifespan
(MLSP; Barja, 2004; Pamplona et al., 2004; Hulbert,
2005). Firstly, because PUFAs are located at the
mitochondrial membrane, they are prone to lipid
peroxidation, which results in extensive production of
radical oxygen species (ROS) (reviewed in Hulbert,
2005). Radical oxygen species readily interact with
macromolecules, cause accumulating tissue damage, and
eventually lead to death from age according to the 'free
radical theory' (Brand, 2000; Hulbert, 2003; Barja,
2004; Speakman, 2005a). Secondly, PUFAs are thought to
raise metabolic rate, i.e. one of the factors that seems
to be associated with short lifespans (Rubner, 1908;
Pearl, 1928; Daan et al., 1996; but see Speakman et al.,
2003, 2004). Species with a high basal metabolic rate
(BMR), such as small mammals, also have high membrane
PUFA contents (Hulbert, 2005). Furthermore, there is
experimental evidence that PUFAs increase the activity
of membrane associated metabolically active proteins,
such as the sodium pump (Wu et al., 2001; Turner et al.,
2003). Based on these observations, the 'membrane
pacemaker theory' of metabolism (Hulbert & Else, 1999,
2000, 2004, 2005; Hulbert, 2003, 2005) suggests that
high amounts of membrane PUFAs lead to elevated BMR and
increased peroxidation of fatty acids, and thus impair
MLSP in mammals.

Among PUFAs, one particular fatty acid, docosahexaenoic acid
(DHA), which predominantly occurs in membranes of retina and
brain, was shown to significantly increase Na+-K+-ATPase
molecular activity (Turner et al., 2003). Therefore, DHA is
thought to act as a particularly important pacemaker of BMR
(Hulbert & Else, 1999, 2000, 2004, 2005). Accordingly,
numerous studies have demonstrated a negative correlation
between DHA content in tissue membranes and MLSP in mammals
and birds (Pamplona et al., 1998, 1999a; Portero-Otin et al.,
2001; Hulbert, 2003, 2005).

As pointed out by Speakman (2005b), there are, however, two
major problems with these simple correlations between
membrane fatty acid composition, metabolism, and longevity.
First, correlations between these variables may be merely due
to the fact that all of them are correlated to body weight, a
most 'pervasive trait that influences all aspects of
organismal biology' (Speakman, 2005b), but may have no actual
functional relation to each other. Second, species in
comparative data sets may not represent independent
replicates, due to phylogenetically caused correlations.
Fortunately, both of these problems can be overcome by
employing statistical procedures that adjust for body weight
and phylogenetic effects. In his reanalysis of relations
between DHA, MLSP, and BMR, Speakman (2005b) found that
indeed, after statistically adjusting for both body weight
effects and phylogeny, there was no significant relation
between MLSP and BMR, and only a weak relationship between
MLSP and DHA. With regard to membrane fatty acids, this
analysis was, however, limited to DHA, and to eight mammalian
species only, which may have been one of the reasons for the
observed lack of correlations with MLSP.

Therefore, we collected data on DHA and other PUFA muscle
phospholipid contents in 42 mammalian species (Fig. 1, Table
1) and re-examined their possible effect on MLSP. In short,
we found that after adjusting for the influence of body
weight and phylogenetic correlations, MLSP was neither
related to DHA content, nor to membrane unsaturation (i.e.
PUFA content or number of double bonds). Interestingly,
however, MLSP significantly decreased as the class of
phospholipid n-3 PUFAs (including DHA) increased, and,
consequently n-6 PUFAs decreased. This effect of the n-3/n-6
PUFA ratio appears to be independent from metabolic rate
because we found no relation between any characteristic of
membrane fatty acid composition and BMR.

[Taka]

On Feb 5, 10:43 pm, MattLB <mat...@angelfire.com> wrote:
> On Feb 5, 1:16 am, Taka <taka0...@gmail.com> wrote:
>
> > On Feb 4, 10:37 pm, MattLB <mat...@angelfire.com> wrote:
> > > It seems you have too, as you've answered a different
> > > question to the one I asked.
>
> > Yes, I agree that anything except saturated fatty acid can
> > be "deleteriously oxidised in the body" but the question
> > is how fast and how bad!
>
> In the escalating conditions of an atheroma it makes very
> little difference which fatty acid is present - they're all
> being exposed to highly oxidising conditions.

And what induces this oxidising conditions in the first place?
Does AA sound so unfamiliar in this respect? If you are
convinced that saturated fatty acids oxidize as easy as PUFAs
like if you were pouring them into the fire there is no point
in continuing this discussion further ...

> > Have you ever heard about something called the iodine
> > number?
>
> Addition reactions have nothing to do with the hydrogen
> abstraction processes involved in lipid peroxidation. The
> iodine reaction is done with an excess to ensure all the
> double bonds are converted to give a count. Nothing to do
> with stability in vivo.

Are you saying that the number of double bonds doesn't play a
role in susceptibility to oxidation in vivo? Then why fish oil
depletes VitE while saturated fat doesn't? Well even if it was
true you still have to deal with the enzymatic oxidation to
compounds like LTA4 or PGH2 which spontaneously react with
different biomolecules directly contributing to aging and
chronic diseases and which cannot be formed from the non-EFAs
and saturated fat ...

> > > I think you need to readhttp://www.ncbi.nlm.nih.gov/pub-
> > > med/17156083?ordinalpos=4&itool=Entrez...
>
> > > which states there's no correlation between number of
> > > double bonds and lifespan, nor DHA content and lifespan.
>
> > You are obsessed with that particular single paper
>
> First time I've seen or mentioned it.

OK, I remembered it was DZ who was repeatedly bringing that
paper on me in the past.

> > Too bad I don't have access to the full text but it seems
> > to be just another "statistical play"
>
> They did the study precisely because others had statistical
> flaws. I've tagged on the introduction from the paper below.

Thanks for that.

> > embarrassing themselves even in the Abstract by giving it
> > a title "N-3 polyunsaturated fatty acids impair lifespan"
> > if they want to contradict the membrane pacemaker theory
> > of aging.
>
> The title is a strange choice, but refers to an imbalance
> between omega 3 and 6 being correlated with reduced
> lifespan. DHA content alone has no relationship with
> lifespan, nor do any other PUFA.

OK I see their point. They are not targeting the "unsaturation
hypothesis" but the metabolic rate and still mistakenly
suppose that the rate is related to the membrane PUFA content.
There are many papers showing that the MLSP is not related to
metabolic rate neither to body size. Compare e.g. the
man-sized rodent Capybara (MLSP 10 years, herbivore like iron)
to the mole rat (30 years) and if you argue the low metabolic
rate of mole rat take the bat (25 years) or the birds (some
are meat eaters). Even in the same species - CR in humans
decreases membrane unstauration and I think thyroid does the
same while boosting the metabolic rate. Or the queen bee -
take royal jelly and significantly increase lifespan as well
as the membrane saturation. Even the lab versus wild mice are
good examples - they feed them vegetable oils in the lab. I
don't think this is pure coincidence or a statistical error in
so many studies which I don't have time to cite right now.

Taka

> MattLB
>
> Introduction
>
> Polyunsaturated fatty acids (PUFA) are essential components
> of dietary fats and have a number of important cellular
> functions including regulation of enzymes, ion pumps, and
> immune responses (Stubbs & Smith, 1984; Pond & Mattacks,
> 1998). In the context of aging, however, there are several
> arguments suggesting that PUFAs may adversely affect maximum
> lifespan (MLSP; Barja, 2004; Pamplona et al., 2004; Hulbert,
> 2005). Firstly, because PUFAs are located at the
> mitochondrial membrane, they are prone to lipid
> peroxidation, which results in extensive production of
> radical oxygen species (ROS) (reviewed in Hulbert,
> 2005). Radical oxygen species readily interact with
> macromolecules, cause accumulating tissue damage, and
> eventually lead to death from age according to the
> 'free radical theory' (Brand, 2000; Hulbert, 2003;
> Barja, 2004; Speakman, 2005a). Secondly, PUFAs are
> thought to raise metabolic rate, i.e. one of the
> factors that seems to be associated with short
> lifespans (Rubner, 1908; Pearl, 1928; Daan et al.,
> 1996; but see Speakman et al., 2003, 2004). Species
> with a high basal metabolic rate (BMR), such as small
> mammals, also have high membrane PUFA contents
> (Hulbert, 2005). Furthermore, there is experimental
> evidence that PUFAs increase the activity of membrane
> associated metabolically active proteins, such as the
> sodium pump (Wu et al., 2001; Turner et al., 2003).
> Based on these observations, the 'membrane pacemaker
> theory' of metabolism (Hulbert & Else, 1999, 2000,
> 2004, 2005; Hulbert, 2003, 2005) suggests that high
> amounts of membrane PUFAs lead to elevated BMR and
> increased peroxidation of fatty acids, and thus impair
> MLSP in mammals.
>
> Among PUFAs, one particular fatty acid, docosahexaenoic acid
> (DHA), which predominantly occurs in membranes of retina and
> brain, was shown to significantly increase Na+-K+-ATPase
> molecular activity (Turner et al., 2003). Therefore, DHA is
> thought to act as a particularly important pacemaker of BMR
> (Hulbert & Else, 1999, 2000, 2004, 2005). Accordingly,
> numerous studies have demonstrated a negative correlation
> between DHA content in tissue membranes and MLSP in mammals
> and birds (Pamplona et al., 1998, 1999a; Portero-Otin et
> al., 2001; Hulbert, 2003, 2005).
>
> As pointed out by Speakman (2005b), there are, however, two
> major problems with these simple correlations between
> membrane fatty acid composition, metabolism, and longevity.
> First, correlations between these variables may be merely
> due to the fact that all of them are correlated to body
> weight, a most 'pervasive trait that influences all aspects
> of organismal biology' (Speakman, 2005b), but may have no
> actual functional relation to each other. Second, species in
> comparative data sets may not represent independent
> replicates, due to phylogenetically caused correlations.
> Fortunately, both of these problems can be overcome by
> employing statistical procedures that adjust for body weight
> and phylogenetic effects. In his reanalysis of relations
> between DHA, MLSP, and BMR, Speakman (2005b) found that
> indeed, after statistically adjusting for both body weight
> effects and phylogeny, there was no significant relation
> between MLSP and BMR, and only a weak relationship between
> MLSP and DHA. With regard to membrane fatty acids, this
> analysis was, however, limited to DHA, and to eight
> mammalian species only, which may have been one of the
> reasons for the observed lack of correlations with MLSP.
>
> Therefore, we collected data on DHA and other PUFA muscle
> phospholipid contents in 42 mammalian species (Fig. 1, Table
> 1) and re-examined their possible effect on MLSP. In short,
> we found that after adjusting for the influence of body
> weight and phylogenetic correlations, MLSP was neither
> related to DHA content, nor to membrane unsaturation (i.e.
> PUFA content or number of double bonds). Interestingly,
> however, MLSP significantly decreased as the class of
> phospholipid n-3 PUFAs (including DHA) increased, and,
> consequently n-6 PUFAs decreased. This effect of the n-3/n-6
> PUFA ratio appears to be independent from metabolic rate
> because we found no relation between any characteristic of
> membrane fatty acid composition and BMR.

[Mattlb]

On Feb 6, 1:28 pm, Taka <taka0...@gmail.com> wrote:
> On Feb 5, 10:43 pm, MattLB <mat...@angelfire.com> wrote:
>
> > On Feb 5, 1:16 am, Taka <taka0...@gmail.com> wrote:
>
> > > On Feb 4, 10:37 pm, MattLB <mat...@angelfire.com> wrote:
> > > > It seems you have too, as you've answered a different
> > > > question to the one I asked.
>
> > > Yes, I agree that anything except saturated fatty acid
> > > can be "deleteriously oxidised in the body" but the
> > > question is how fast and how bad!
>
> > In the escalating conditions of an atheroma it makes very
> > little difference which fatty acid is present - they're
> > all being exposed to highly oxidising conditions.
>
> And what induces this oxidising conditions in the
> first place?

Various things, principally passing through the epithelium
and then becoming lodged outside the blood where you don't
have the same antioxidant protection. Once taken up into foam
cells they're deliberately attacked with radicals and when
the foam cell bursts, out comes lots of oxidised fat to
continue the cycle.

> Does AA sound so unfamiliar in this respect?

AA is a cellular signalling molecule. It can't create an
oxidising environment - unless it's already oxidised and then
you have a chicken and egg situation if you think it's all
about the AA.

> If you are convinced that saturated fatty acids oxidize as
> easy as PUFAs

No, that *all* PUFA will become oxidised in the highly
damaging environment described above. It's like saying a
particular sunscreen is more stable than another so has a
higher protection factor. If you spend enough time in the sun,
you're going to burn whatever sunscreen you've got on.

Lipoproteins trapped in the artery wall are subject to far
greater oxidative stress than those in the blood, where the
antioxidants should prevent oxidation of all the lipids.

> > > Have you ever heard about something called the iodine
> > > number?
>
> > Addition reactions have nothing to do with the hydrogen
> > abstraction processes involved in lipid peroxidation. The
> > iodine reaction is done with an excess to ensure all the
> > double bonds are converted to give a count. Nothing to do
> > with stability in vivo.
>
> Are you saying that the number of double bonds doesn't play
> a role in susceptibility to oxidation in vivo?

I'm saying the iodine number has nothing to do with stability.
The number of double bonds can have a simple statistical
importance in that the more a molecule has the more likely it
is one of them will collide with a radical, but that ignores
the fact that some of them will be buried in the bilayer
because of the shape the molecules have.

> There are many papers showing that the MLSP is not related
> to metabolic rate neither to body size.

As a general rule the "big body weight-lower metabolic
rate-longer life" pattern is true. There are exceptions (like
humans) but they are clear exceptions and usually result from
a side effect of some other adaptation.

> Compare e.g. the man-sized rodent Capybara (MLSP 10 years,
> herbivore like iron) to the mole rat (30 years)

The naked mole rat has much higher levels of markers of lipid
oxidation than comparable species who live a fraction of its
lifespan, so the "lipid oxidation model of aging" isn't
sufficient. I'm not sure if it's been posted here, but here's
a link to a description of an experiment that showed mole rats
have *more* oxidative damage than mice, yet live much longer.

http://www.newswise.com/articles/view/524122/

In terms of some of the markers you and monty1945
sometimes quote:

"The level of isoprostanes found in the urine was 10 times
higher in the naked mole-rat, the level of malondialdehyde in
liver tissue was twice as high and isoprostane levels in heart
tissue was two-and-a- half times the level of the mice."

The researcher theorizes that it may simply be that there are
lower oxygen levels in the mole rat's natural environment and
that's why they live longer, rather than anything special
about their lipid makeup (which doesn't seem to protect them
from oxidative stress in the lab).

> argue the low metabolic rate of mole rat take the bat (25
> years) or the birds (some are meat eaters).

Flying animals have to have additional mechanisms to deal with
the higher oxygen requirements of flight, with the fortuitous
side effect that they also prolong life.

MattLB

[Jay]

> The naked mole rat has much higher levels of markers of
> lipid oxidation than comparable species who live a fraction
> of its lifespan, so the "lipid oxidation model of aging"
> isn't sufficient. I'm not sure if it's been posted here, but
> here's a link to a description of an experiment that showed
> mole rats have *more* oxidative damage than mice, yet live
> much longer.
>
> http://www.newswise.com/articles/view/524122/

Note, in above study, higher ox-stress measurments in lab may
have been due to the fact that naked moles typically live in a
reduced oxygen enironment. See below for other theories:

Exp Gerontol. 2007 Nov; Membrane phospholipid composition may
contribute to exceptional longevity of the naked mole-rat
(Heterocephalus glaber): a comparative study using shotgun
lipidomics.

Phospholipids containing highly polyunsaturated fatty acids
are particularly prone to peroxidation and membrane
composition may therefore influence longevity. Phospholipid
molecules, in particular those containing docosahexaenoic acid
(DHA), from the skeletal muscle, heart, liver and liver
mitochondria were identified and quantified using
mass-spectrometry shotgun lipidomics in two similar-sized
rodents that show an approximately 9-fold difference in
maximum lifespan. The naked mole rat is the longest-living
rodent known with a maximum lifespan of >28 years. Total
phospholipid distribution is similar in tissues of both
species; DHA is only found in phosphatidylcholines (PC),
phosphatidylethanolamines (PE) and phosphatidylserines (PS),
and DHA is relatively more concentrated in PE than PC. Naked
mole-rats have fewer molecular species of both PC and PE than
do mice. DHA-containing phospholipids represent 27-57% of all
phospholipids in mice but only 2-6% in naked mole-rats.
Furthermore, while mice have small amounts of
di-polyunsaturated PC and PE, these are lacking in naked
mole-rats. Vinyl ether-linked phospholipids (plasmalogens) are
higher in naked mole-rat tissues than in mice. The lower level
of DHA-containing phospholipids suggests a lower
susceptibility to peroxidative damage in membranes of naked
mole- rats compared to mice. Whereas the high level of
plasmalogens might enhance membrane antioxidant protection in
naked mole-rats compared to
mice. Both characteristics possibly contribute to the
exceptional longevity of naked mole-rats and may
indicate a special role for peroxisomes in this extended
longevity. PMID: 18029129

J Gerontol A Biol Sci Med Sci. 2006 Oct; Oxidation-resistant
membrane phospholipids can explain longevity differences among
the longest- living rodents and similarly-sized mice.

Underlying causes of species differences in maximum life span
(MLS) are unknown, although differential vulnerability of
membrane phospholipids to peroxidation is implicated. Membrane
composition and longevity correlate with body size; membranes
of longer-living, larger mammals have less polyunsaturated
fatty acid (PUFA). We determined membrane phospholipid
composition of naked mole-rats (MLS > 28.3 years) and
similar-sized mice (MLS = 3-4 years) by gas-liquid
chromatography to assess if the approximately 9x MLS
difference could be explained. Mole-rat membrane composition
was unchanged with age. Both species had similar amounts of
membrane total unsaturated fatty acids; however, mice had 9
times more docosahexaenoic acid (DHA). Because this n-3PUFA is
most susceptible to lipid peroxidation, mole- rat membranes
are substantially more resistant to oxidative stress than are
mice membranes. Naked mole-rat peroxidation indices,
calculated from muscle and liver mitochondrial membranes,
concur with those predicted by MLS rather than by body size,
suggesting that membrane phospholipid composition is an
important determinant of longevity. PMID: 17077193

Rejuvenation Res. 2007 Dec; Theoretical paper: exploring
overlooked natural mitochondria-rejuvenative intervention: the
puzzle of bowhead whales and naked mole rats.

There is an imperative need for exploring and implementing
mitochondria-rejuvenative interventions that can bridge the
current gap toward the step-by step realization of strategies
for engineered negligible senescence (SENS) agenda. Recently
discovered in mammals, natural mechanism mitoptosis-a
selective "suicide" of mutated mitochondria-can facilitate
continuous purification of mitochondrial pool in an organism
from the most reactive oxygen species (ROS)- producing
mitochondria. Mitoptosis, which is considered to be the first
stage of ROS-induced apoptosis, underlies follicular atresia
(a "quality control" mechanism in female germline cells that
eliminates most germinal follicles in female embryos).
Mitoptosis can be also activated in adult postmitotic somatic
cells by evolutionary conserved phenotypic adaptations to
intermittent oxygen restriction (IOR) and synergistically
acting intermittent caloric restriction (ICR). IOR and ICR are
common in mammals and seem to underlie extraordinary longevity
and augmented cancer resistance in bowhead whales (Balena
mysticetus) and naked mole rats (Heterocephalus glaber).
Furthermore, in mammals IOR can facilitate continuous stromal
stem cells-de-pendent tissue repair. A comparative analysis of
IOR and ICR mechanisms in both mammals, in conjunction with
the experience of decades of biomedical and clinical research
on emerging preventative, therapeutic, and rehabilitative
modality-the intermittent hypoxic training/therapy
(IHT)-indicates that the notable clinical efficiency of IHT is
based on the universal adaptational mechanisms that are common
in mammals. Further exploration of natural
mitochondria-preserving and - rejuvenating strategies can help
refinement of IOR- and ICR-based synergistic protocols, having
value in clinical human rejuvenation. PMID: 18072884

[Taka]

On Feb 7, 12:09 am, MattLB <mat...@angelfire.com> wrote:
> On Feb 6, 1:28 pm, Taka <taka0...@gmail.com> wrote:
>
>
>
> > On Feb 5, 10:43 pm, MattLB <mat...@angelfire.com> wrote:
>
> > > On Feb 5, 1:16 am, Taka <taka0...@gmail.com> wrote:
>
> > > > On Feb 4, 10:37 pm, MattLB <mat...@angelfire.com>
> > > > wrote:
> > > > > It seems you have too, as you've answered a
> > > > > different question to the one I asked.
>
> > > > Yes, I agree that anything except saturated fatty acid
> > > > can be "deleteriously oxidised in the body" but the
> > > > question is how fast and how bad!
>
> > > In the escalating conditions of an atheroma it makes
> > > very little difference which fatty acid is present -
> > > they're all being exposed to highly oxidising
> > > conditions.
>
> > And what induces this oxidising conditions in the first
> > place?
>
> Various things, principally passing through the epithelium
> and then becoming lodged outside the blood where you don't
> have the same antioxidant protection. Once taken up into
> foam cells they're deliberately attacked with radicals and
> when the foam cell bursts, out comes lots of oxidised fat to
> continue the cycle.
>
> > Does AA sound so unfamiliar in this respect?
>
> AA is a cellular signalling molecule. It can't create an
> oxidising environment - unless it's already oxidised and
> then you have a chicken and egg situation if you think it's
> all about the AA.
>
> > If you are convinced that saturated fatty acids oxidize as
> > easy as PUFAs
>
> No, that *all* PUFA will become oxidised in the highly
> damaging environment described above. It's like saying a
> particular sunscreen is more stable than another so has a
> higher protection factor. If you spend enough time in the
> sun, you're going to burn whatever sunscreen you've got on.
>
> Lipoproteins trapped in the artery wall are subject to far
> greater oxidative stress than those in the blood, where the
> antioxidants should prevent oxidation of all the lipids.

This would put factors leading to the arterial wall tears as
the No.1 primary cause of atherosclerosis - makes me think
about the sharp uric acid crystals again. Then we may end up
at the fructose again.

> > > > Have you ever heard about something called the iodine
> > > > number?
>
> > > Addition reactions have nothing to do with the hydrogen
> > > abstraction processes involved in lipid peroxidation.
> > > The iodine reaction is done with an excess to ensure all
> > > the double bonds are converted to give a count. Nothing
> > > to do with stability in vivo.
>
> > Are you saying that the number of double bonds doesn't
> > play a role in susceptibility to oxidation in vivo?
>
> I'm saying the iodine number has nothing to do with
> stability. The number of double bonds can have a simple
> statistical importance in that the more a molecule has the
> more likely it is one of them will collide with a radical,
> but that ignores the fact that some of them will be buried
> in the bilayer because of the shape the molecules have.
>
> > There are many papers showing that the MLSP is not related
> > to metabolic rate neither to body size.
>
> As a general rule the "big body weight-lower metabolic
> rate-longer life" pattern is true. There are exceptions
> (like humans) but they are clear exceptions and usually
> result from a side effect of some other adaptation.
>
> > Compare e.g. the man-sized rodent Capybara (MLSP 10 years,
> > herbivore like iron) to the mole rat (30 years)
>
> The naked mole rat has much higher levels of markers of
> lipid oxidation than comparable species who live a fraction
> of its lifespan, so the "lipid oxidation model of aging"
> isn't sufficient. I'm not sure if it's been posted here, but
> here's a link to a description of an experiment that showed
> mole rats have *more* oxidative damage than mice, yet live
> much longer.
>
> http://www.newswise.com/articles/view/524122/
>
> In terms of some of the markers you and monty1945
> sometimes quote:
>
> "The level of isoprostanes found in the urine was 10
> times higher in the naked mole-rat, the level of
> malondialdehyde in liver tissue was twice as high and
> isoprostane levels in heart tissue was two-and-a- half
> times the level of the mice."
>
> The researcher theorizes that it may simply be that there
> are lower oxygen levels in the mole rat's natural
> environment and that's why they live longer, rather than
> anything special about their lipid makeup (which doesn't
> seem to protect them from oxidative stress in the lab).

I would like to see how long the rats lived in the laboratory.
Taking them out of their natural habitat which is quite
different from the lab puts a lot of stress on them (more than
on the mice I guess). Also they should not measure only the
lipid peroxide markers but also the DHA/AA content in the same
animals. They may be feeding them vegetable oil-rich food
which alters the lipid composition quite a bit. Mice may be
more resistant to the vegetable oils because they are
naturally used to eating seeds.

Also they suggest that the rats are more resistant to the
acute bouts of oxidative stress what is exactly what you get
with more saturated membranes. The higher "oxidative stress
markers" may actually represent their natural signaling which
they can afford thanks to the more resistant cellular
components.

> > argue the low metabolic rate of mole rat take the bat (25
> > years) or the birds (some are meat eaters).
>
> Flying animals have to have additional mechanisms to deal
> with the higher oxygen requirements of flight, with the
> fortuitous side effect that they also prolong life.

And the mechanisms are nothing more than the more saturated
membranes. And the side effect is they need to keep their body
warm at 40oC due to the membrane fluidity.

Taka

> MattLB

[Mattlb]

On Feb 7, 3:05 am, Taka <taka0...@gmail.com> wrote:
> On Feb 7, 12:09 am, MattLB <mat...@angelfire.com> wrote:

> > Lipoproteins trapped in the artery wall are subject to
> > far greater oxidative stress than those in the blood,
> > where the antioxidants should prevent oxidation of all
> > the lipids.
>
> This would put factors leading to the arterial wall tears as
> the No.1 primary cause of atherosclerosis

Physical damage such as that caused by high blood pressure is
indeed the best way to get an atheroma, and branch point in
arteries are typically where they appear first. I've also read
(no citation to hand) that a single cigarette doubles the
number of dead endothelial cells floating around in the blood.

> > The researcher theorizes that it may simply be that there
> > are lower oxygen levels in the mole rat's natural
> > environment and that's why they live longer, rather than
> > anything special about their lipid makeup (which doesn't
> > seem to protect them from oxidative stress in the lab).
>
> I would like to see how long the rats lived in the
> laboratory.

Well the photo on the site is of a 15 year old, and they'd
only know the exact age if they're reared it. Actually I've
just found an abstract from this year from one of authors of
the original paper which claims "Naked mole-rats live in
captivity for more than 28.3 years,"

http://www.ncbi.nlm.nih.gov/pubmed/18180931?ordinalpos=1&i-
tool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubm-
ed_RVDocSum

There's also the comment in the full text:

"Even from young age naked mole-rats exhibit high levels of
oxidative damage to DNA lipids and proteins without any
impact upon physiological function yet they continue to
thrive for an additional 26 years while young mice have less
than 3 years of life left"

This is the problem with monty1945's obsession with molecular
level detail, he misses out the fact that it's the physiology
that matters most to survival. While I'm not suggesting for a
second that lipid peroxidation is irrelevant, it's clearly not
sufficient to explain aging.

One or both of the following seems to be the papers that the
article I linked to is based on:

http://www.ncbi.nlm.nih.gov/pubmed/17054663?ordinalpos=10&ito-
ol=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RV-
DocSum http://www.ncbi.nlm.nih.gov/pubmed/17129214?ordinalpos-
=7&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pub-
med_RVDocSum

> Also they should not measure only the lipid peroxide
> markers but also the DHA/AA content in the same animals.
> They may be feeding them vegetable oil-rich food which
> alters the lipid composition quite a bit. Mice may be more
> resistant to the vegetable oils because they are naturally
> used to eating seeds.

It's possible to come up with explanations that try and
explain away the results, but the simple fact is that mole
rats have a different (and in your view more protective) fatty
acid composition to mice, but when exposed to the same level
of oxygen there's more oxidative damage to the mole rats. They
don't have better antioxidant defences, and their lipids don't
protect them.

> Also they suggest that the rats are more resistant to the
> acute bouts of oxidative stress what is exactly what you get
> with more saturated membranes.

Acute incidents don't cause aging though. Besides, whatever's
in the membrane is kind of a secondary issue when the DNA is
being damaged.

> The higher "oxidative stress markers" may actually represent
> their natural signaling which they can afford thanks to the
> more resistant cellular components.

Oxidative damage to DNA and proteins (also higher in the mole
rats) isn't a signal of anything other than damage.

> > Flying animals have to have additional mechanisms to deal
> > with the higher oxygen requirements of flight, with the
> > fortuitous side effect that they also prolong life.
>
> And the mechanisms are nothing more than the more saturated
> membranes.

There's more to it than that! Also, many birds eat seeds/nuts
so they're getting lots of PUFA in their diet.

> And the side effect is they need to keep their body warm at
> 40oC due to the membrane fluidity.

The higher metabolic demands of flight mean their resting
metabolic rate is also higher. Still at least you recognise
the importance of membrane fluidity and don't deny they even
exist like monty1945.

MattLB

[Mattlb]

On Feb 6, 5:44 pm, jay <jaym1...@hotmail.com> wrote:
> > The naked mole rat has much higher levels of markers of
> > lipid oxidation than comparable species who live a
> > fraction of its lifespan, so the "lipid oxidation model of
> > aging" isn't sufficient. I'm not sure if it's been posted
> > here, but here's a link to a description of an experiment
> > that showed mole rats have *more* oxidative damage than
> > mice, yet live much longer.
>
> >http://www.newswise.com/articles/view/524122/
>
> Note, in above study, higher ox-stress measurments in lab
> may have been due to the fact that naked moles typically
> live in a reduced oxygen enironment.

I did mention that, but since they still reach the maximum
lifespan in the lab it can't be a very significant difference.

>See below for other theories:
>
> Exp Gerontol. 2007 Nov; Membrane phospholipid composition
> may contribute to exceptional longevity of the naked
> mole-rat (Heterocephalus glaber): a comparative study using
> shotgun lipidomics.

Note that this paper is by one of the researchers of the
article I quoted, so isn't at odds with it.

> J Gerontol A Biol Sci Med Sci. 2006 Oct; Oxidation-resistant
> membrane phospholipids can explain longevity differences
> among the longest- living rodents and similarly-sized mice.

As is this one.

> Rejuvenation Res. 2007 Dec; Theoretical paper: exploring
> overlooked natural mitochondria-rejuvenative intervention:
> the puzzle of bowhead whales and naked mole rats.

I think mitochondrial aspects are likely to be more
important than simple levels of lipid oxidation in general.
It could be that the higher oxidative damage in mole rats
leads to higher turnover of mitochondria, maintaining a
healthier population overall.

MattLB

[Taka]

On Feb 7, 10:54 pm, MattLB <mat...@angelfire.com> wrote:
> Physical damage such as that caused by high blood pressure
> is indeed the best way to get an atheroma, and branch point
> in arteries are typically where they appear first. I've
> also read (no citation to hand) that a single cigarette
> doubles the number of dead endothelial cells floating
> around in the blood.

It seems to me that the damage comes first and the high
blood pressure second. You need to make the arteries stiff
by AGEs/ALEs before the high blood pressure appears. Anyway
so people who are not killing their endothelial cells by
toxins can live safely with high cholesterol compared to
those who do?

> > > The researcher theorizes that it may simply be that
> > > there are lower oxygen levels in the mole rat's natural
> > > environment and that's why they live longer, rather than
> > > anything special about their lipid makeup (which doesn't
> > > seem to protect them from oxidative stress in the lab).
>
> > I would like to see how long the rats lived in the
> > laboratory.
>
> Well the photo on the site is of a 15 year old, and they'd
> only know the exact age if they're reared it. Actually I've
> just found an abstract from this year from one of authors of
> the original paper which claims "Naked mole-rats live in
> captivity for more than 28.3 years,"
>
> http://www.ncbi.nlm.nih.gov/pubmed/18180931?ordinalpos=1&it-
> ool=Entrez...
>
> There's also the comment in the full text:
>
> "Even from young age naked mole-rats exhibit high levels of
> oxidative damage to DNA lipids and proteins without any
> impact upon physiological function yet they continue to
> thrive for an additional 26 years while young mice have
> less than 3 years of life left"
>
> This is the problem with monty1945's obsession with
> molecular level detail, he misses out the fact that it's the
> physiology that matters most to survival. While I'm not
> suggesting for a second that lipid peroxidation is
> irrelevant, it's clearly not sufficient to explain aging.
>
> One or both of the following seems to be the papers that the
> article I linked to is based on:
>
> http://www.ncbi.nlm.nih.gov/pubmed/17054663?ordinalpos=10&i-
> tool=Entre...http://www.ncbi.nlm.nih.gov/pubmed/17129214?or-
> dinalpos=7&itool=Entrez...
>
> > Also they should not measure only the lipid peroxide
> > markers but also the DHA/AA content in the same animals.
> > They may be feeding them vegetable oil-rich food which
> > alters the lipid composition quite a bit. Mice may be more
> > resistant to the vegetable oils because they are naturally
> > used to eating seeds.
>
> It's possible to come up with explanations that try and
> explain away the results, but the simple fact is that mole
> rats have a different (and in your view more protective)
> fatty acid composition to mice, but when exposed to the same
> level of oxygen there's more oxidative damage to the mole
> rats. They don't have better antioxidant defences, and their
> lipids don't protect them.

As you can read at:

http://news-info.wustl.edu/tips/page/normal/10217.html

the "beasts" seem to actually live only 3 or 4 years with
that level of damage, the rest they shut down their
metabolism. But topor or hibernation generally requires
higher PUFA content to prevent membrane damage at low
temperature so this is puzzling.

> > Also they suggest that the rats are more resistant to the
> > acute bouts of oxidative stress what is exactly what you
> > get with more saturated membranes.
>
> Acute incidents don't cause aging though. Besides,
> whatever's in the membrane is kind of a secondary issue when
> the DNA is being damaged.

I would really like to see the kind of DNA damage they
actually measured. In the Pol gamma mutator mouse high levels
of mitochondrial DNA damage occur as POINT mutations which
don't affect the lifespan. But when the mutations are rather
large DELETIONS (see Khrapko, substantia nigra) they nicely
correlate with shortened lifespan.

Also the place of the damage is important. Muscle tissue
naturally undergoes substantial oxidative damage which is
actually used as guidance to strengthening the tissue (by the
satellite cells). On the other hand damage of the stem cell
pool would certainly lead to decreased MLSP. Also have they
looked at the damage in the brain? Excreting the isoprostanes
in urine is nothing more than a sign of good maintenance.

The mole rat may have very good stem cell maintenance
mechanisms (including more saturated membranes in them) which
it can afford because of evolving on an energy dense (starchy
tubers) diet. The stroma is disposable/repairable if the stem
cell niches are healthy with low rates of damage.

Also why are they living the same 30 years in the protected
lab environment as well as in the wild? People lived just 40
years in the wild while they are dying at 80 in the modern
protected environment. I think the rat has more damage in the
lab than in its natural habitat and therefore his lifespan
doesn't increase.

> > The higher "oxidative stress markers" may actually
> > represent their natural signaling which they can afford
> > thanks to the more resistant cellular components.
>
> Oxidative damage to DNA and proteins (also higher in the
> mole rats) isn't a signal of anything other than damage.
>
> > > Flying animals have to have additional mechanisms to
> > > deal with the higher oxygen requirements of flight, with
> > > the fortuitous side effect that they also prolong life.
>
> > And the mechanisms are nothing more than the more
> > saturated membranes.
>
> There's more to it than that! Also, many birds eat
> seeds/nuts so they're getting lots of PUFA in their diet.

And despite of that they are not putting them in their cell
membranes like people, there must be a good reason for that.

Taka

[Mattlb]

Taka wrote:
> On Feb 7, 10:54 pm, MattLB <mat...@angelfire.com> wrote:
> > Physical damage such as that caused by high blood pressure
> > is indeed the best way to get an atheroma, and branch
> > point in arteries are typically where they appear first.

> It seems to me that the damage comes first and the high
> blood pressure second.

High blood pressure directly causes damage, particularly at
branch points, which is why it's so significant that atheromas
appear there too. This doesn't require the arteries to be
stiffened.

>You need to make the arteries stiff by AGEs/ALEs before the
>high blood pressure appears.

Not at all. There are lots of ways to raise blood pressure
that don't require arteriosclerosis to have occurred. High
adrenaline levels due to stress is an obvious one.

> As you can read at:
>
> http://news-info.wustl.edu/tips/page/normal/10217.html
>
> the "beasts" seem to actually live only 3 or 4 years with
> that level of damage, the rest they shut down their
> metabolism.

I assume you're referring to these comments:

"Naked mole rats appear to deal with oxidative stress in
pulses, largely due to their ability to essentially shut down
their metabolism when there are hardships, such as lack of
food. In this way, mole rats may be able to rid their body of
harmful reducing agents and poisons more easily during these
metabolic pulses."

In the lab there are no hardships. Food isn't a problem, nor
is temperature, so there would be no reason to have to shut
down their metabolism, yet they still live 28 years. I assume
the researchers would have noticed and commented upon a
periodic shutdown of their lab animals if the pulses were
in-built rather than in response to environmental hardhship.

> I would really like to see the kind of DNA damage they
> actually measured.

One of the abstracts refers to 8-OHdG measurement, which is a
measure of oxidation (and then repair) of guanosine
nucleotides. Since guanine is most prone to oxidative damage,
8-OHdG is a general measure of DNA damage.

> In the Pol gamma mutator mouse high levels of mitochondrial
> DNA damage occur as POINT mutations which don't affect the
> lifespan. But when the mutations ar rather large DELETIONS
> (see Khrapko, substantia nigra) they nicely correlate with
> shortened lifespan.

Free radical damage is far more likely to produce random point
mutations than insertion/deletion mutations, if indeed they
can cause them at all. General DNA damage can interfere with
transcription and replication even if there's no change in the
coding sequence.

> Also the place of the damage is important.

Well, they have damaged livers.

> Also have they looked at the damage in the brain?

I can't get the full texts so I don't know.

> Excreting the isoprostanes in urine is nothing more than a
> sign of good maintenance.

That's flawed logic unless you're claiming they're
actively excreted rather than simply not being reabsorbed
by the kidney.

> Also why are they living the same 30 years in the protected
> lab environment as well as in the wild? People lived just 40
> years in the wild while they are dying at 80 in the modern
> protected environment.

I doubt there's much danger of predation or accidental death
in the wild for mole rats, whereas people in the wild had both
of those problems, plus sun-exposure etc.

> I think the rat has more damage in the lab than in its
> natural habitat and therefore his lifespan doesn't increase.

This hypothetical damage precisely balances the benefits of
the protected lab environment to keep the max lifespan exactly
the same does it? Can't you see how contrived that it is? A
much simpler explanation is that their longevity is
independent of either environment.

> > There's more to it than that! Also, many birds eat
> > seeds/nuts so they're getting lots of PUFA in their diet.
>
> And despite of that they are not putting them in their cell
> membranes like people,

What's your evidence for that?

MattLB

[Taka]

On Feb 8, 11:10 pm, MattLB <mat...@angelfire.com> wrote:
> >You need to make the arteries stiff by AGEs/ALEs before the
> >high blood pressure appears.
>
> Not at all. There are lots of ways to raise blood pressure
> that don't require arteriosclerosis to have occurred. High
> adrenaline levels due to stress is an obvious one.

Good point. As you can read on the Ray Peat's site the adrenal
hormones are permanently elevated when you are hypothyroid.
Adrenaline helps mobilizing glucose what is normally taken
care of by thyroid. So it compensates for the thyroid which is
destroyed by nothing else than dietary PUFAs. You can reverse
the condition by coconut oil - see:

www.raypeat.com http://www.coconutoil.com/thyroid_health.htm

> > I would really like to see the kind of DNA damage they
> > actually measured.
>
> One of the abstracts refers to 8-OHdG measurement, which is
> a measure of oxidation (and then repair) of guanosine
> nucleotides. Since guanine is most prone to oxidative
> damage, 8-OHdG is a general measure of DNA damage.

8-oxoG is exactly the simple non-bulky type of DNA damage
which doesn't shorten lifespan. It can be readily repaired by
specific glycosylases or mismatch repair or even tolerated by
DNA polymerases in an error-free manner.

> > In the Pol gamma mutator mouse high levels of
> > mitochondrial DNA damage occur as POINT mutations which
> > don't affect the lifespan. But when the mutations ar
> > rather large DELETIONS (see Khrapko, substantia nigra)
> > they nicely correlate with shortened lifespan.
>
> Free radical damage is far more likely to produce random
> point mutations than insertion/deletion mutations, if indeed
> they can cause them at all. General DNA damage can interfere
> with transcription and replication even if there's no change
> in the coding sequence.

Now you have to distinguish the simple modifications caused by
direct oxidation like the above mentioned 8-oxoG which result
in simple base substitutions at worst and the bulky lesions
blocking replication and leading to frameshifts and large
deletions. What do you think that causes the BULKY DNA
lesions? It's nothing else than lipid peroxides derived from
the long chain PUFAs! So you get the hydroxyl radicals or
peroxynitrite first attacking the PUFAs, if they are around in
the mitochondrial membrane, and then the oxidized PUFAs attach
to DNA bases like guanine at the N2 position. They can even
directly crosslink proteins to DNA (ever heard of
levuglandins?) and that becomes a real mess causing double
strand breaks and clastogenicity ...

I suspect that what they have measured in that paper was not
even 8- oxoG inside the DNA itself but only 8-oxoGTP in the
nucleotide pool which is only DNA precursor and would never be
incorporated into the DNA if there is enough energy around to
synthesize the correct undamaged dNTPs. The correct DNA
precursors are preferred by the DNA polymerases compared to
their oxidized versions.

> > Also the place of the damage is important.
>
> Well, they have damaged livers.

An organ with the greatest regeneration capability ...

> > > There's more to it than that! Also, many birds eat
> > > seeds/nuts so they're getting lots of PUFA in their
> > > diet.
>
> > And despite of that they are not putting them in their
> > cell membranes like people,
>
> What's your evidence for that?

Every "expert" will tell you that people are overloaded with
AA because of high consumption of Omega-6 rich vegetable oils
- is that enough evidence that you are what you eat? Grass fed
cows have more Omega-3 as they are present in the grass. The
birds do have more saturated lipids in the membranes compared
to rodents which also thrive on seeds/nuts ...

Let's end this marathon, we clearly need more research on the
mole rats to figure out what is truly behind their "extreme"
longevity - I am betting on the lipid theory. Or wait if Monty
ends up dead with clogged arteries in 10 years what he should
according to your reasoning.

Taka

[Marshall P]

Ron Peterson wrote:
> On Jan 30, 3:43 pm, Durand <durand.sincl...@gmail.com>
> wrote:
>> 1) OMEGA 3 IS BENDY: Omega 3 fats are called Omega 3
>> because they have a double join in their carbon chain
>> every three carbon atoms.

> That's correct.

I don't get it. According to my nutrition textbook (Whitney
and Rolfes, _Understanding Nutrition_), "A fatty acid has two
ends, designated the methyl (CH3) end and the carboxyl, or
acid (COOH), end." "Standard chemistry notation begins
counting carbons at the acid end. The number of carbons the
fatty acid contains comes first, followed by a colon and
another number that indicates the number of double bonds; next
comes a semicolon followed by a number or numbers indicating
the positions of the double bonds. Thus the notation for
linoleic acid, an 18-carbon fatty acid with two double bonds
between carbons 9 and 10 and between carbons 12 and 13, is
18:2;9,12." "Because fatty acid chains are lengthened by
adding carbons at the acid end of the chain, chemists use the
omega system of notation to ease the task of identifying them.
The omega system begins counting carbons at the methyl end.
The number of carbons the fatty acid contains comes first,
followed by a colon and the number of double bonds; next comes
the omega symbol [I just spell out the word "omega"] and
number indicating the position of the double bond nearest the
methyl end. Thus linoleic acid with its first double bond at
the sixth carbon from the methyl end would be noted 18:2omega6
in the omega system."

So an omega-3 fatty acid ought to be one in which the first
double bond, counting from the methyl end, is at position 3,
NOT one having "a double join ... every three carbon atoms."

However, considering linolenic (18:3omega3), eicosapentanoic
(20:5omega3), and docosahexanoic (22:6omega3) acids, I see
that they're represented in standard notation as
18:3;9,12,15, 20:5;5,8,11,14,17, and
21:6;4,7,10,13,16,19, respectively!

In other words (except for the bonds closest to the carboxyl
end), they just *happen* (?) to have double bonds at every
third carbon acid!

Unfortunately, those are the only three listed in the brief
table on that page.

Is it just coincidence that in the case of those three fatty
acids, Durand is right? Is there a logical reason for there
being a double bond, not just three carbons from the methyl
end, but at *every* third carbon along the chain?

--
Marshall Price of Miami Known to Yahoo as d021317c

[Mattlb]

On Mar 17, 7:17 am, Marshall Price <d0213...@yahoo.com> wrote:
> MattLB wrote:
> > On Feb 1, 12:28 pm, Durand <durand.sincl...@gmail.com>
> > wrote:
> >> That's a great answer, Matt. I thought cholesterol was a
> >> fat, rather than a lipid trucked around by a protein.
> >> Thanks for clearing that up
>
> > Lipid is just an umbrella term that covers fats, oils and
> > some other hydrophobic molecules. Cholesterol *is* a fat
> > in the general sense, but a very different sort of fat to
> > the type containing fatty acids.
>
> > MattLB
>
> According to the Merck Index 13 (#2221), it's the "principal
> sterol of the higher animals. Found in all body tissues, esp
> in the brain, spinal cord, and in animal fats or oils. Main
> constituent of gallstones. Prepd commercially from the
> spinal cord of cattle by petr ether extraction of the
> nonsaponifiable matter. Also produced from wool grease.
> Cholesterol from animal organs always contains cholestanol
> (dihydrocholesterol) and other satd sterols." "USE:
> Pharmaceutic aid (emulsifying agent)."
>
> How can it be considered a fat in any sense?

There are many senses in which it's a fat - it's a greasy
solid at room temperature; it's insoluble in water; it's found
in the lipid bilayer membrane of cells; it dissolves in and
dissolves other fats; it's transported on the same
lipoproteins as other fats; it's synthesized from the same
starting molecules as fatty acids and stored in the cell along
with, and bound to, fatty acids.

MattLB

[Marshall P]

Marshall Price wrote:

snip

> So an omega-3 fatty acid ought to be one in which the first
> double bond, counting from the methyl end, is at position 3,
> NOT one having "a double join ... every three carbon atoms."
>
> However, considering linolenic (18:3omega3), eicosapentanoic
> (20:5omega3), and docosahexanoic (22:6omega3) acids, I see
> that they're represented in standard notation as
> 18:3;9,12,15, 20:5;5,8,11,14,17, and
> 22:6;4,7,10,13,16,19, respectively!
>
> In other words (except for the bonds closest to the carboxyl
> end), they just *happen* (?) to have double bonds at every
> third carbon acid!

snip

> Is it just coincidence that in the case of those three fatty
> acids, Durand is right? Is there a logical reason for there
> being a double bond, not just three carbons from the methyl
> end, but at *every* third carbon along the chain?

Incidentally, I found in /Molecular Biology of the Cell/ 13,
Panel 2-1, p 110, under "alternating double bonds":

"The carbon chain can include double bonds. If these are on
alternate carbon atoms, the bonding electrons move within the
molecule, stabilizing the structure by a phenomenon called
resonance."

So *if* resonance played a role in these omega-3 fatty acid
carbon chains, this would account for double bonds at every
third carbon.

Does it?

--
Marshall Price of Miami Known to Yahoo as d021317c

[Marshall P]

MattLB wrote:
> On Feb 1, 12:28 pm, Durand <durand.sincl...@gmail.com>
> wrote:
>> On Feb 1, 2:17 am, MattLB <mat...@angelfire.com> wrote:
>>
>>
>>
>>> On Jan 30, 9:43 pm, Durand <durand.sincl...@gmail.com>
>>> wrote:
>>>> Hi, Why is it that Omega 3 fats makes good cholesterol?
>>>> From what I've read about its chemistry, it shouldn't.
>>>> Could you read the assumptions I've made, and see where
>>>> my logic is wrong?
>>>> 3) GOOD CHOLESTEROL IS DENSE: Omega 3 acids make "good
>>>> cholesterol". One reason your body makes cholesterol
>>>> in the first place is because to patch up dents in
>>>> your arteries, caused by blood flow wearing away the
>>>> insides. "Good cholesterol" is considered good because
>>>> it is tightly packed, and solid, and therefore fills
>>>> the gap like putty. On the other hand "bad
>>>> cholesterol" is big and fluffy, not at all dense, and
>>>> doesn't patch the holes up properly. What's more, it
>>>> tends to get washed off the hole later on, and sits
>>>> around in the blood stream forming clots.
>>> I think part of the problem here is the use of the terms
>>> good and bad cholesterol. What they actually refer to is
>>> two types of lipoprotein in the blood. Low density
>>> lipoprotein (LDL) is called "bad cholesterol" because it
>>> is richer in cholesterol than the other lipids it carries
>>> and is the one that ends up lodged in artery walls (which
>>> is bad). High density lipoprotein (HDL) is mostly protein
>>> with actually quite a small amount of cholesterol. It is
>>> called "good cholesterol" because it picks up cholesterol
>>> from around the body and delivers it to the liver. The
>>> terms good and bad cholesterol therefore don't refer to
>>> cholesterol molecules made from different fatty acids,
>>> they refer to different proteins that carry cholesterol
>>> around the body. The density issue is a tricky one too, as
>>> although HDL is more dense than LDL it's not significant
>>> that it is. What *is* signficant is that some people have
>>> what's called an LDL-B phenotype where they make LDL
>>> that's smaller and denser than normal and enters the
>>> artery wall 40-50% faster than normal LDL. Smaller LDL
>>> particles are also more easily oxidised. When it comes to
>>> lipoproteins, bigger and fluffier is actually better.
>>> MattLB
>> That's a great answer, Matt. I thought cholesterol was a
>> fat, rather than a lipid trucked around by a protein.
>> Thanks for clearing that up
>
> Lipid is just an umbrella term that covers fats, oils and
> some other hydrophobic molecules. Cholesterol *is* a fat in
> the general sense, but a very different sort of fat to the
> type containing fatty acids.
>
> MattLB

According to the Merck Index 13 (#2221), it's the "principal
sterol of the higher animals. Found in all body tissues, esp
in the brain, spinal cord, and in animal fats or oils. Main
constituent of gallstones. Prepd commercially from the spinal
cord of cattle by petr ether extraction of the
nonsaponifiable matter. Also produced from wool grease.
Cholesterol from animal organs always contains cholestanol
(dihydrocholesterol) and other satd sterols." "USE:
Pharmaceutic aid (emulsifying agent)."

How can it be considered a fat in any sense?

--
Marshall Price of Miami Known to Yahoo as d021317c