Orotate as a β-Alanine Donor for Anserine and Carnosine Biosynthesis, and Effects of Actinomycin D and Azauracil on Their Pathway

Abstract

The chemical and radiochemical analysis of free amino acids and dipeptides in the liver and skeletal muscle of rats injected with orotate-6-¹⁴C were performed with the preparative amino acid autoanalyzer. The concentration of β-alanine was found to be 7 μmoles/100 g in liver, but much lower than that in the skeletal muscle. Anserine and carnosine were present at high levels in the skeletal muscle, but at low levels in liver. The radioactivity of orotate-¹⁴C injected was found to be distributed in β-alanine (1/4 of the activity incorporated into RNA), anserine (1/50 of the activity of β-alanine) and carnosine (1/500 of the activity of β-alanine), but was not in other free amino acids in liver. The incorporation of radioactivity was higher in liver than in skeletal muscle. It seems that anserine and carnosine are biosynthesized in the liver and accumulated or maintained in the skeletal muscles. Actinomycin D stimulated the formation of β-alanine and anserine, but reduced the formation of carnosine. 6-Aza-uracil stimulated a pathway from β-alanine to carnosine via anserine, by promoting the formation of β-alanine.