From: Robert J. Bradbury (bradbury@aeiveos.com)
Date: Thu Jan 10 2002 - 01:47:26 MST
On Wed, 9 Jan 2002, Harvey Newstrom wrote:
> One caveat here. Worms use coenzyme Q-9, while humans use coenzyme Q-10.
> The study showed that coenzyme Q-9 might be bad for worms. They wonder if
> coenzyme Q-10 is therefore bad for humans. A good question, but hardly
> conclusive.
>
> I sure want to see more about this. Coenzyme Q-10 is part of my personal
> life-extension program to help fight heart disease.
Harvey, this area is getting even *more* complex than I want
to think about (unfortunately). I too am a big fan of Q-10.
But, the article in the most recent Nature about superoxide
potentially regulating the uncoupling proteins makes me cautious.
The mitochondria generate a hydrogen ion (H+) gradient by
pumping H+ ions out thru their membranes. CoQ10 is
an essential factor in this process. The H+ gradient is
used to generate ATP as the ions flow back through the
F0-F1-ATP synthase molecule. This is a great strategy
because one is able to more closely couple a lot of
small energy carriers (the H+ gradient) to a large energy
carrier (ATP) [think converting cents into $] with few
losses. In contrast when ATP (in $) is spent (by many
enzymes in the body) you may have the problem that everything
is priced in increments of $0.25 -- and because you
pay in ATP ($), the store keeps anything you over the
actual price (i.e. it doesn't "make change").
Now, as the H+ ion gradient gets steeper (lots of
inputs to generate it, or few ADP molecules to feed
the F0-F1-ATP synthase to run the gradient down) the
electron transport chain in the mitochondria gets backed up.
(View it as a queue waiting to get your oil changed.)
As that happens more free radicals (impatient customers)
get generated.
As I've discussed before there are "active" mechanisms
for unleashing the UCP (uncoupling) proteins to run
down the H+ gradient and generate heat. All warm-blooded
species use this to maintain body temperature. When
your body "feels" that it is cold, hormones get released
to activate UCP proteins and generate heat.
The recent Nature article *suggested* (the scientists
were clear to say more work was required to determine
whether this was an in vivo phenomena) that superoxide
also served to activate the UCP proteins.
This makes a *lot* of sense -- if your H+ gradient gets
too high and is going to generate a lot of free radicals,
then the superoxide radical could serve as a fail-safe
molecule to activate the UCP proteins and reduce the
gradient to non-damaging levels.
As I've mentioned before -- evidence suggests that CoQ10
is involved in both the electron transport chain to
generate the H+ gradient *as well as* the UCP protein
mediated process to diminish the H+ gradient. So it
is an essential component of both charging and decharging
the gradient.
Now, both of those mechanisms I have historically viewed
as "good". *BUT* if CoQ10 *also* serves as a general
antioxidant and can mitigate excess superoxide, then
it may serve to interfere with the normal processes
that use superoxide to activate the UCP proteins to
keep the H+ gradient below levels that generate
excessive quantities of free radicals. In this
case excess CoQ10 (above that needed for the electron
transport chain and the UCP H+ ion transport) could
indeed be detrimental.
I know -- it shocked me too! It just goes to show how
there may be genetic programs that have been quite
well "tuned" and that tuning them with nutrients will
not work -- we have to get control of the program itself.
I won't go into the details but there are lots of things
one could do to leave the superoxide mediated effects
intact in the mitochondria while mitigating damage they
might cause elsewhere.
Hope that provides some insight. If you have more questions
email me directly so I'll know its something I should provide
greater detail on.
Robert
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