Mammalian isovalthine metabolism

Abstract

Summary 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 μmol/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 (α‐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.

Characteristics of Nutrition and Metabolism in Dogs and Cats

“…Interestingly, male cats produce more felinine than females (Hendriks et al 2004). In cats but not dogs, cysteine is also used to generate felinine and isobuteine from isopentenyl pyrophosphate (formed from acetyl-CoA) and valine, respectively, via cooperation of the liver and kidneys (Che et al 2021;Hendriks et al 2008;Rutherfurd-Markwick et al 2005). Cysteine participates in all these reactions in the form of glutathione.…”

Amino acid nutrition and metabolism in domestic cats and dogs

“…This finding indicates that cats can adapt well to dietary AA intake through modulating AA oxidation. In contrast to dogs, cats, like other Felidae species, use leucine and valine to synthesize isovalthine and isobuteine, respectively, with hitherto unknown physiological function [ 96 , 97 ]. We are not aware of studies to compare tissue-specific or whole-body BCAA metabolism among animal species (including cats).…”

“…Cats synthesize felinine, isovalthine, and isobuteine from cysteine plus acetyl-CoA, cysteine plus isovaleryl-CoA (a metabolite of leucine), and cysteine plus isobutyryl-CoA (a metabolite of valine) as unique sulfur-containing AAs [ 96 , 97 ]. In intact adult male cats, the rates of urinary excretion of felinine and isovalthine are 122 and 1.8 μmol/kg BW/d, respectively [ 96 ]. At present, there are no quantitative data on the urinary excretion of isobuteine by cats.…”