[Substrate inhibition in the tricarboxylic acid cycle].
It has been shown in the experiments on rat liver mitochondria under glucose hexo-kinase load that excess of substrates of (1-20 mM) pyruvate, acetate, propionate, pent-4-enoate and malate may induce oxidation of NAD(P)H and inhibition of mitochondrial respiration (by 20-50% and more) due to a decreased rate of hydrogen production by tricarboxylic acid cycle. It has been concluded from the analysis of mathematical models and metabolite-testings which remove this inhibition that for pyruvate and acetate this inhibition is an autocatalytic one. It is related to a decreased level of CoA and oxaloacetate due to the formation of "traps" such as acetyl-CoA and alpha-kotoglutarate. For propionate and pent-4-enoate in the bicarbonate-free medium suppression of the flux in the cycle is concerned with a decreased level of CoA, acetyl-CoA and succionoyl CoA due to the accumulation of propionyl-CoA. It seems to be also concerned with the inhibition of citrate-synthetase and alpha-ketoglutarate-dehydrogenase by propionyl-CoA. Malate (in the presence of malonate) can inhibit respiration at the expense of direct inhibition of citrate-synthetase.
D000085:Acetates / Q000378:metabolism; D000818:Animals; D002952:Citric Acid Cycle; D005229:Fatty Acids, Monounsaturated; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D066298:In Vitro Techniques; D008293:Malates / Q000378:metabolism; D008297:Male; D008930:Mitochondria, Liver / Q000378:metabolism*; D010084:Oxidation-Reduction; D010101:Oxygen Consumption; D011422:Propionates / Q000378:metabolism; D011773:Pyruvates / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013379:Substrate Specificity
D000085:Acetates; D005229:Fatty Acids, Monounsaturated; D005231:Fatty Acids, Unsaturated; D008293:Malates; D011422:Propionates; D011773:Pyruvates; C009785:4-pentenoic acid
Substratnoe ugnetenie v tsikle trikarbonovykh kislot.