Biosynthesis and degradation of carnosine and turnover rate of its constituent amino acids in rats.

Abstract

The biosynthesis and destruction of anserine and carnosine in the rat were investigated in vivo using radioactive β-alanine, histidine and methylhistidine. In the normal rat, the incorporation of ¹⁴C-histidine and ¹⁴C-β-alanine into carnosine was found to proceed at significant rates, but their incorporation into anserine was hardly detectable. Radioactive anserine arising from ³H-N^π-methylhistidine was detected in gastrocnemius muscle of the rat pretreated with β-alanine. Neither anserine nor carnosine biosynthesis was found in liver, but was found in gastrocnemius muscle. At 8 hr after the administration of a single dose of ¹⁴C-histidine or ¹⁴C-β-alanine, the incorporation of radioactivity into carnosine attained a plateau, and then maintained the level for the investigated period. Incorporation of ¹⁴C-histidine into carnosine was increased about 2-fold when rats were injected in advance with f-alanine. The half-lives of histidine and β-alanine were 0.67 and 0.41 hr in liver, and 3.6 and 2.3 hr in gastrocnemius muscle, respectively. β-Alanine and histidine in rat gastrocnemius muscle disappeared at the rates of 39 and 29 nmol/wet tissue (g)/hr, respectively. The half-life of carnosine, as was determined from the decrease in carnosine contents in the gastrocnemius muscle of a rat fed a histidine-free diet, was 29 days. The rate constant of carnosine biosynthesis in rat gastrocnemius muscle was 0.321 μmol/DNA (mg)/day, that is, 0.286 μmol/wet tissue (g)/day.