Elfarra A A
Department of Comparative Biosciences, University of Wisconsin School of Veterinary Medicine, Madison 53706-1102, USA.
Chem Biol Interact. 1995 Apr 28;96(1):47-55. doi: 10.1016/0009-2797(94)03582-s.
Several xenobiotics and their corresponding cysteine S-conjugates are metabolized in vivo to cysteine S-conjugate sulfoxides and/or N-acetylcysteine S-conjugate sulfoxides. Homocysteine S-conjugates, such as methionine and ethionine, are also metabolized in vivo to sulfoxides. The enzymatic basis for these metabolic reactions is not known. Recently, the rat liver and kidney S-benzyl-L-cysteine S-oxidase activities were found to be associated with flavin-containing monooxygenases that are structurally and immunochemically related to known FMO1 isoforms. Further evidence for FMO1 being the major FMO isoform involved in S-benzyl-L-cysteine sulfoxidation was obtained from kinetic studies with cDNA-expressed rabbit FMOs. Endogenous cysteine S-conjugates, e.g. cysteinylcatecholamines, cysteinylleukotrienes, lanthionine and djenkolic acid may also be substrates for FMOs, since S-benzyl-L-cysteine can be considered a model for these compounds. Methionine, an endogenous homocysteine S-conjugate, was shown to be a substrate for cDNA-expressed rabbit FMO1, FMO2, and FMO3, however, the methionine sulfoxidation reaction was preferentially catalyzed by FMO3. These results suggest that FMOs may also play a role in the in vivo metabolism of endogenous homocysteine S-conjugates.
几种外源性物质及其相应的半胱氨酸S-共轭物在体内代谢为半胱氨酸S-共轭亚砜和/或N-乙酰半胱氨酸S-共轭亚砜。同型半胱氨酸S-共轭物，如蛋氨酸和乙硫氨酸，在体内也代谢为亚砜。这些代谢反应的酶学基础尚不清楚。最近，发现大鼠肝脏和肾脏的S-苄基-L-半胱氨酸S-氧化酶活性与含黄素单加氧酶有关，这些酶在结构和免疫化学上与已知的FMO1同工型相关。通过对cDNA表达的兔FMOs进行动力学研究，进一步证明FMO1是参与S-苄基-L-半胱氨酸亚砜氧化的主要FMO同工型。内源性半胱氨酸S-共轭物，如半胱氨酰儿茶酚胺、半胱氨酰白三烯、羊毛硫氨酸和jenkolic酸也可能是FMOs的底物，因为S-苄基-L-半胱氨酸可被视为这些化合物的模型。蛋氨酸是一种内源性同型半胱氨酸S-共轭物，已被证明是cDNA表达的兔FMO1、FMO2和FMO3的底物，然而，蛋氨酸亚砜氧化反应优先由FMO3催化。这些结果表明，FMOs也可能在内源性同型半胱氨酸S-共轭物的体内代谢中起作用。
