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Science Forum Index » Life Extension Forum » Role of thioredoxin in low NAD+ situations
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| kofi |
 Posted: Tue Jan 13, 2004 1:20 pm |
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Eur J Biochem. 2003 Mar;270(6):1036-42. Related Articles, Links
Click here to read
2-Oxo acid dehydrogenase complexes in redox regulation.
Bunik VI.
A.N.Belozersky Institute of Physico-Chemical Biology, Moscow State
University, Russia.
A number of cellular systems cooperate in redox regulation,
providing metabolic responses according to changes in the oxidation (or
reduction) of the redox active components of a cell. Key systems of
central metabolism, such as the 2-oxo acid dehydrogenase complexes, are
important participants in redox regulation, because their function is
controlled by the NADH/NAD+ ratio and the complex-bound
dihydrolipoate/lipoate ratio. Redox state of the complex-bound lipoate
is an indicator of the availability of the reaction substrates (2-oxo
acid, CoA and NAD+) and thiol-disulfide status of the medium.
Accumulation of the dihydrolipoate intermediate causes inactivation of
the first enzyme of the complexes. With the mammalian pyruvate
dehydrogenase, the phosphorylation system is involved in the
lipoate-dependent regulation, whereas mammalian 2-oxoglutarate
dehydrogenase exhibits a higher sensitivity to direct regulation by the
complex-bound dihydrolipoate/lipoate and external SH/S-S, including
mitochondrial thioredoxin. Thioredoxin efficiently protects the
complexes from self-inactivation during catalysis at low NAD+. As a
result, 2-oxoglutarate dehydrogenase complex may provide succinyl-CoA
for phosphorylation of GDP and ADP under conditions of restricted NAD+
availability. This may be essential upon accumulation of NADH and
exhaustion of the pyridine nucleotide pool. Concomitantly, thioredoxin
stimulates the complex-bound dihydrolipoate-dependent production of
reactive oxygen species. It is suggested that this side-effect of the
2-oxo acid oxidation at low NAD+in vivo would be overcome by cooperation
of mitochondrial thioredoxin and the thioredoxin-dependent peroxidase,
SP-22.
Publication Types:
* Review
* Review, Tutorial
PMID: 12631263 [PubMed - indexed for MEDLINE] |
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