Metabolism and metabolic effects of ketoacids.

Administration of any of the three branched-chain amino or ketoacids necessarily yields the respective aminated or deaminated compound because the ubiquitous enzyme, branched-chain amino acid transaminase, catalyzes the reversible transfer of amino groups between the three amino acids and their ketoacids. Branched-chain amino acid transaminase activity increases by unknown mechanisms in certain physiological and nutritional conditions and also in the presence of an excess of alpha-ketoisocaproate. This compound directly stimulates the enzyme to increase catalytic efficiency. The effect is rapid in onset and specific for the keto analogue of leucine. Irreversible branched-chain ketoacid degradation is initiated by a mitochondrial dehydrogenase enzyme which (like branched-chain amino acid transaminase) reacts with all three ketoacids and is important in regulating the pool size and proportions of branched-chain amino acids. In rats; hepatic dehydrogenase activity is induced by feeding branched-chain ketoacids. In muscle, branched-chain ketoacids or their degradation products affect both energy supply and the rate of net protein synthesis. An improved understanding of ketoacid metabolism will lead to more effective use of these compounds in treating patients with diseases of nitrogen retention.