Enzymatic Cleavage of S-(Isopropylcarboxymethyl) Glutathione into Isovalthine*

The Role of Glutathione and Glutathione S‐Transferases in Mercapturic Acid Biosynthesis

“…The glutathione-isovaleric acid conjugate is probably catabolized to isovalthine by the same enzymes that catabolize the glutathione conjugates of mercapturic acid precursors (Kuwaki, 1965). Other cysteine derivatives isolated or detected include S-(p-carboxyn-propy1)-L-cysteine (also known as P-isobuteine) and S-(P-carboxyethyl)-L-cysteine present in normal child urine (Ohmori, Shimomura, Azumi, and Mizuhara, 1965), and S-(carboxymethy1)cysteine present in some animal tissues and in the urine of hypertensive and diabetic patients (Ubuka, Kodama, and Mizuhara, 1967).…”

Mammalian isovalthine metabolism

“…However this is not the same form as that identified by Ohmori and colleagues (1963) as being present in urine (l‐isovalthine). A later paper by Kuwaki (1965) showed that (+) or (−) GSIV gave rise to L‐ and L‐ allo ‐isovalthine, respectively, and that cleavage of (+) GSIV by guinea‐pig glutathionase occurs at a greater rate than (−) GSIV.…”

“…Only Fukutome (1961) and Kuwaki (1964) have used cats to study isovalthine biosynthesis. The latter is interesting, as cats have been shown to be the Values are presented as mean ± SEM * Taken from Hendriks and colleagues (2004) Review of isovalthine metabolism…”

“…This precursor, S-(iso-propylcarboxymethyl) glutathione (GSIV), was the result of a conjugation reaction between glutathione and potassium isovalerate, and when subjected to acid hydrolysis, yielded isovalthine, glutamic acid and glycine. When l-cysteine was used instead of glutathione, neither GSIV nor isovalthine were detected, indicating that it is not just the cysteine moiety that is required for synthesis of GSIV (Kuwaki, 1964). Kuwaki (1964) later demonstrated that the liver homogenates of cats, rats and pigs were also able to synthesize GSIV, and that 14 Cisovaleric acid could be incorporated into GSIV by guinea-pig liver homogenates.…”

“…When l-cysteine was used instead of glutathione, neither GSIV nor isovalthine were detected, indicating that it is not just the cysteine moiety that is required for synthesis of GSIV (Kuwaki, 1964). Kuwaki (1964) later demonstrated that the liver homogenates of cats, rats and pigs were also able to synthesize GSIV, and that 14 Cisovaleric acid could be incorporated into GSIV by guinea-pig liver homogenates. In an effort to partially purify the enzyme responsible for GSIV synthesis, Kuwaki (1964) carried out a simple fractionation procedure on guinea-pig liver based on precipitation at different ammonium sulphate concentrations.…”