Burning fats without producing ATP

mikalra at my-deja.com mikalra at my-deja.com
Wed Jan 19 12:26:34 EST 2000


Date:
             Tue, 18 Jan 2000 23:45:22 -0800
       From:
             "Michael Sherman" <sherm at symdyn.com>


[I stumbled on the following abstract by accident.  I think it says
that "NutriGuard Research" has discovered a novel and potentially
very lucrative way to modify the behavior of mitochondria
through supplementation.  When burning fat, mitochondria
normally produce CO2 as a waste product and ATP as useful output.
This modification causes them instead to produce just CO2 and heat!
That means the body's fat is consumed without yielding any useful
energy, leading to "a remarkable rate of body-fat loss and
thermogenesis".]

According to the abstract, this is accomplished by uncoupling of the
electron transport chain.  My understanding is limited, but AFAIK this
means lots of state 4 activity -- mucho heat, mini ATP, and more freee
radicals than you can shake mtSOD at.  The formula, in orther words, is
a recipe for accelerated aging, according to MiFR and others.

This might partly explain Hagen et al's results, in which ALCAR
supplementation INCREASED oxidative stress -- except that Hagen also
found increasesed ATP generation, so something else is going on.

Aubrey?

-Michael

The way I picture what they've done is: shift the mitochondria
into neutral and then step on the gas until the tank is empty.

Has anyone every heard of this outfit?  Are they developing a product
which could cause people to burn up all their unwanted body fat by
taking a pill and running a fever?  More importantly, should we be
investing in this company before the billions start to roll in?

Any molecular biologists out there care to comment on whether
this would really work in humans?  Also, would the reaction
described be so dirty as to cause severe mitochondrial damage?

sherm

TI- Pyruvate and hydroxycitrate/carnitine may synergize to promote
reverse
    electron transport in hepatocyte mitochondria, effectively
'uncoupling'
    the oxidation of fatty acids.
AU- McCarty MF; Gustin JC
AD- NutriGuard Research, Encinitas, CA 92024, USA.
SR- Med Hypotheses, 52:407-16, 1999 May
AB- In a recent pilot study, joint administration of pyruvate,
    hydroxycitrate (HCA), and carnitine to obese subjects was
associated
with
    a remarkable rate of body-fat loss and thermogenesis, strongly
suggestive
    of uncoupled fatty-acid oxidation. Hepatocytes possess an
uncoupling
    mechanism--reverse electron transport--that enables fasting
ketogenesis
    to proceed independent of respiratory control. Electrons entering
the
    respiratory chain at the coenzyme Q (CoQ) level via FAD-dependent
acyl
    coA dehydrogenase, can be driven 'up' the chain by the
electrochemical
    proton gradient to reduce NAD+; if these electrons are then
shuttled to
    the cytoplasm, returning to the respiratory chain at the CoQ level,
the
    net result is heat generation at the expense of the proton
gradient,
    enabling the uncoupled flow of electrons to oxygen. Pyruvate's
bariatric
    utility may stem from its ability to catalyze the rapid transport
of
    high-energy electrons from mitochondria to the cytoplasm, thus
    stimulating electron shuttle mechanisms. By enabling rapid
mitochondrial
    uptake of fatty acids and thus disinhibiting hepatocyte
ketogenesis,
    HCA/carnitine should initiate reverse electron transport:
concurrent
    amplification of electron shuttle mechanisms by pyruvate can be
expected
    to accelerate this reverse electron transport, thereby decreasing
the
    electrochemical proton gradient. As a result, hepatocytes may be
able to
    convert fatty acids to CO2 and heat with little net generation of
ATP.
    These considerations suggest that it may be feasible to render
    hepatocytes functionally equivalent to activated brown fat, such
that
    stored fat can be selectively oxidized in the absence of caloric
    restriction. Other measures which enhance the efficiency of
hepatocyte
    electron shuttle mechanisms may increase the efficacy of this
strategy.


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