Dietary amino acid analogs alter activities of some amino acid-metabolizing enzymes in rat liver

Abstract

Dietary amino acid analogs often strongly and selectively modify rat tissue amino acid profiles. These effects are accompanied by altered activities of several enzymes of amino acid catabolism. In a preliminary study, activities of hepatic serine dehydratase (SDH), glutamate-pyruvate (GPT), GABA and tyrosine (TAT) aminotransferases, and ornithine carbamoyltransferase (OCT) were high in rats fed diets containing a mixture (3%) of analogs (norleucine, norvaline, α-aminophenylacetate, and α-aminooctanoate); pyruvate kinase (PK) was low. Raising the protein content of the diet often lessened the effect. Analog effects on SDH, GPT, and PK occurred within 2 days, but not within 4 hr. After adaptation to a 50% protein diet that raised SDH and GPT and lowered PK, rats were fed a 6% protein diet with or without the analogs; the normal decline in initially high SDH and GPT was slowed within 4 days in rats fed the analogs, whereas the normal increase in PK induced by a low protein diet was strongly blocked by day 1. In rats fed a 6% amino acid diet, dietary norleucine stimulated branched-chain ketoacid dehydrogenase (BCKAD) activity about 290%, had lesser effects on SDH, GPT, and OCT, and did not alter PK, TAT, or branched-chain aminotransferase; norvaline stimulated only BCKAD (85%). In rats fed an 8% amino acid mixture limiting in leucine. SDH activity was stimulated (up to 800%), depending on norleucine level in the diet, and was lessened by added dietary leucine; similar, but less striking patterns occurred for GPT. If all indispensable amino acids were fed in adequate amounts, SDH and GPT were not stimulated by norleucine. Overall, analog effects were usually more prominent in rats fed suboptimal diets.