PNAS (USA) 98(4):1416-1421 (13 Feb 2001)
Uncoupling proteins 2 and 3 are highly active H+ transporters and
highly nucleotide sensitive when activated by coenzyme Q (ubiquinone)
Echtay, K. S. et al.
Points out that Coenzyme Q (Q10) is essential for the function
of the uncoupling proteins in adipose tissue and skeletal muscle.
Q10 is known to be a factor required for electron transport to
produce the hydrogen ion gradient essential for ATP production.
This study now shows it is essential to uncouple the H+ ion
gradient as well.
The "uncoupling" is an essential part of heat production by
adipose tissue and skeletal muscle in warm blooded animals.
(One is "burning" glucose to produce the H+ ion gradient
and then uncoupling it (allowing the gradient to run
back downhill) the net result of this wasteful process
So if you don't have enough CoQ10 (which can happen if you
lean towards vegetarian diets or are on certain cholesterol
lowering medications) then you may not be able to produce
enough ATP (feeling lethargic) or may not be able to burn
off the excess hydrogen ion gradient (feeling cold).
Now *interestingly* enough mitochondria from UCP3 knockout
mice seem to produce higher than normal levels of free
radicals (probably due to a complicated process where the
electron transport chain gets backed up). That would lead
one to suspect that low Q10 levels (disrupting UCP function)
could also lead to higher production of free radicals
(probably accelerating aging).
A lack of CoQ10 and therefore a lack of uncoupling might also
contribute to obesity. This is because if you don't waste some
of the H+ ion gradient through the uncoupling proteins it is going to
get turned into ATP (through ATP synthase) and the excess ATP
will in turn get stored as fat... So when people are fat and
have high cholesterol and their physicians prescribe cholesterol
lowering drugs (that also lower CoQ10 synthesis) their ability to
uncouple the mitochondria decreases and they can't burn off the fat.
These results also suggest that differences in the structure,
levels or regulation of UCP or UCP-like proteins or the regulation
of CoQ10 synthesis between short lived and long lived mammals or
birds might yield some interesting insights into whether or not
they play a role in the longevity of long-lived species due to
their essential role in the function of relief valves for high H+
gradients across the mitochondrial membrane that contribute to
free radical production.
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