Amino acid dehydrogenases 422 Subject

In a muscle at rest, most of the 2-oxo acids produced from transamination of branched chain amino acids are transported to the liver and become subject to oxidation in reactions catalysed by branched-chain 2-oxo acid dehydrogenase complex. During periods of exercise, however, the skeletal muscle itself is able to utilize the oxo-acids by conversion into either acetyl-CoA (leucine and isoleucine) or succinyl-CoA (valine and isoleucine). 

Determination of the level of cytosolic enzymes such as aspartate transaminase, alanine transaminase, and lactate dehydrogenase is part of standard biochemical liver function tests to measure hepatocellular necrosis [2, 101]. Cytosolic enzymes are not subject to genetic variations inherent in microsomal enzyme production. Liver cytosolic enzymes metabolize several molecules, of which galactose and amino acids are typical examples, used for hepatic function tests. 

Experiments with rats have shown that the branched-chain a-keto acid dehydrogenase complex is regulated by covalent modification in response to the content of branched-chain amino acids in the diet. With little or no excess dietary intake of branched-chain amino acids, the enzyme complex is phosphorylated and thereby inactivated by a protein kinase. Addition of excess branched-chain amino acids to the diet results in dephosphoiylation and consequent activation of the enzyme. Recall that the pyruvate dehydrogenase complex is subject to similar regulation by phosphorylation and dephosphorylation (p. 621). 

The precursor of cysteine is the amino acid serine. The biosyntiiesis of this amino acid is mainly regulated by feedback-inhibition. The enzyme, which is sensitive to higher serine concentrations in the cell is the 3-phosphoglycerate dehydrogenase. The serA, coding for this enzyme, was subjected to a mutagenesis procedure to obtain mutants with a reduced feedback inhibition but... 

The horse liver alcohol dehydrogenase, crystallized by my collaborators Bonnichsen and Wassen in 1948, has been subject to much work the last 20 years, both in my lab and others. Its amino acid sequence (374 residues per subunit = molecule) was cleared up by my young collaborator Hans Jornvall working with I. J. Harris in Cambridge from 1967 and then with us in Stockholm. Alcohol dehydrogenases from other sources were also studied in our and many other peoples laboratories. It is at present one of the most intensively studied enzymes in the world. 

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