Aminotransferase, l-amino acid oxidase and β-lyase reactions involving l-cysteine S-conjugates found in allium extracts : Relevance to biological activity?

Abstract

Several cysteine S-conjugates that occur in extracts of garlic and other plants of the allium family possess anti-oxidant properties, and many, including S-allyl- l-cysteine (SAC) and S-allylmercapto- l-cysteine (SAMC), are promising anti-cancer agents. To understand possible biochemical mechanisms contributing to the protective effects, the ability of selected allium-derived l-cysteine S-conjugates to undergo various enzyme-catalyzed transformations was investigated. SAC, SAMC, S-propylmercapto- l-cysteine and S-penta-1,3-dienylmercapto- l-cysteine were shown to be substrates of: (a) highly purified rat kidney glutamine transaminase K (GTK); (b) purified snake venom l-amino acid oxidase; and (c) a cysteine S-conjugate β-lyase present in rat liver cytosol. S-Methylmercapto- l-cysteine was shown to be a substrate of GTK and l-amino acid oxidase, but not of the cysteine S-conjugate β-lyase. Evidence is presented that a major enzyme responsible for the cysteine S-conjugate β-lyase reactions in the rat liver cytosol is γ-cystathionase. The possible role of γ-cystathionase in generating sulfane sulfur from the disulfide-containing cysteine S-conjugates present in allium extracts, and the possible role of this sulfane sulfur in enzyme regulation, targeting of cancer cells and detoxification reactions is discussed. An interesting side finding of the present work is that rat liver mitochondria are more active than rat liver cytosol in catalyzing a cysteine S-conjugate β-lyase reaction with the mitochondrial protoxicant S-(1,1,2,2-tetrafluoroethyl)- l-cysteine (TFEC) at physiological pH and at low substrate concentration.