Tricarboxylic acid cycle biotin

Propionyl-CoA is an intermediary product in the metabo-hsm of four essential amino acids (isoleucine, valine, threonine, and methionine), the aliphatic side-chain of cholesterol, pyrimidines (uracd and thymine), and the final product of the [3-oxidation of odd-chain fatty acids. Under normal circumstances, propionyl-CoA first is converted by a biotin-dependent carboxylase to methylmalonyi-CoA, then to succinyl-CoA by an adenosylcobalamin-dependent mutase, leading to oxidation in the tricarboxylic acid cycle. Primary or secondary defects of these two enzymes were among the first organic acidurias to be discovered, and their natural history has been characterized perhaps better than any other inborn error of organic acid metabolism. 

The a-methyl group in acetyl-CoA undergoes numerous condensation reactions, e.g. 1. carboxylation of acetyl-C)OA to malonyl-CoA by biotin-dependent acetyl- A carboxylase (EC 6.4.1.2) in fatty acid biosynthesis, 2. aldol condensations, e.g. in citrate synthesis (Fig. 2 b) in the tricarboxylic acid cycle. When acetoacetyl-CoA is synthesized from 2 molecules of acelyl-CoA (ester condensation), one molecule enters the reaction as an electrophile, the other as a nucleophile. 

When a molecule of glycerol is formed, a molecule of pyruvate cannot be transformed into ethanol following its decarboxylation into ethanal. In anaerobic conditions, oxaloacetate is the means of entry of pyruvate into the cytosolic citric acid cycle. Although the mitochondria are no longer functional, the enzymes of the tricarboxylic acids cycle are present in the cytoplasm. Pyruvate carboxylase (PC) catalyzes the carboxylation of pyruvate into oxaloacetate. The prosthetic group of this enzyme is biotin it serves as a CO2 transporter. The reaction makes use of an ATP molecule ... 

The final unique stage in the metabolism of L-isoleucine involves the cleavage of 2-methylacetoacetyl-CoA to acetyl-CoA and propionyl-CoA (Section 10.4). The propionyl-CoA is further metabolized to methylmalonyl-CoA by a biotin-dependent carboxylase and subsequently via succinyl-CoA into the tricarboxylic acid cycle. L-Valine is also metabolized ultimately to methylmalonyl-CoA (Section 10.4), and thus these two branched-chain amino acids form the major precursors of propionyl-CoA and methylmalonyl-CoA. Other precursors of propionyl-CoA include methionine, threonine, odd-carbon-number fatty acids and cholesterol. The methyhnalonyl-CoA produced by propionyl-CoA carboxylase occurs as the D(5)-enantiomer and is racemized to the L(/ )-enantiomer by methylmalonyl-CoA racemase. l(/ )-Methylmalonyl-CoA is then metabolized to succinyl-CoA by a vitamin B12-dependent mutase prior to introduction of the modified molecule into the tricarboxylic acid cycle. 

Biotin and folic acid (FA) (Figure 23.1) are two members of the water-soluble B complex vitamins. Biotin plays an important role in gene expression, cell signalling and histone biotinylation, and functions as a coenzyme in the tricarboxylic acid (TCA) cycle. It also functions in the metabolism of fatty... 

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