Transaminative metabolism of alpha-amino-n-butyrate in rats.

alpha-Amino-n-butyrate metabolism was studied in a rt tissue homogenate system using L-[1-14C] alpha-amino-n-butyrate. Transamination was found to be the major route in the liver for the metabolism of L-alpha-amino-n-butyrate based on 44.8 mumoles/g/h of [1-14-C] alpha-ketobutyrate formed in the presence of pyruvate versus 1.2 mumoles/g/h without pyruvate. The pH optimum for the reaction was 9.2. The abilities of other alpha-keto acids to act as a cosubstrate relative to pyruvate were (%): pyruvate, 100; alpha-ketobutyrate, 80; alpha-keto-gamma-methiolbutyrate, 15; phenylpyruvate, 14; alpha-ketoglutarate, p-hydroxyphenylpyruvate and the alpha-keto analogs of the branched-chain amino acids, all less than 10. The apparent Km for alpha-amino-n-butyrate in the liver homogenate was approximately 38 mM and the Km for pyruvate was 5 mM. Kidney was found to have about twice the activity as liver. Activities in brain, heart, diaphragm, muscle and small intestine were negligible. With the exception of serine, no other added amino acids could compete effectively with alpha-amino-n-butyrate for transamination in the rat liver homogenate system. Activity in rat liver was inhibited by aminooxyacetic acid and cycloserine. These results indicate that alpha-amino-n-butyrate is metabolized primarily by a transaminase reaction with pyruvate which occurs almost exclusively in liver and kidney.