Mammalian isovalthine metabolism

Isovalthine is a branched-chain sulphur amino acid, which has been found in the urine of normal cats. The concentrations of isovalthine in the urine of healthy adult cats are approximately 24-66 micromol/l and are not affected by the gender of the cat. Isovalthinuria can be induced in other species (rats, rabbits, guinea-pigs, humans, dogs) following the administration of certain inducing agents such as some hypocholesterolaemic agents, bile acids, hormones or cholesterol precursors. The method of induction of isovalthinuria was studied extensively during the 1960s, and efforts were made to understand its biosynthesis. However, although the origin of the sulphur atom in isovalthine was shown to be from cysteine or methionine, the origin of the carbon skeleton remains unknown. Interest in isovalthine metabolism was generated in part because it was reportedly found in the urine of patients with hypercholesterolaemia. The validity of this finding however, was brought into question following reports that administration of the drug Bromural (alpha-bromoisovalerylurea), to humans results in the generation of compounds which break down to yield isovalthine following acid hydrolysis. This article presents a review and discussion of the experimental data on isovalthine metabolism.