인간 Cystathionine γ-Lyase에 의한 Selenomethionine의 Methylselenol로의 직접분해
Direct Conversion of L-Selenomethionine into Methylselenol by Human Cystathionine γ-Lyase
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초록
Selenium is an essential trace element for mammals, but it is very toxic. Therefore, the control of selenium concentrationsshould be precisely and effectively monitored. Selenium is naturally obtained through foods and seleno-L-methionine (LSeMet)is a major form of selenium. It has been reported that L-SeMet is only converted into Se-adenosyl-L-SeMet. However,a recent study suggested that L-SeMet was directly metabolized into methylselenol (CH3SeH) in mouse liver extract by thereaction of cystathionine γ-lyase (CGL). The canonical reaction of CGL was known to catalyze the cleavage of L-cystathionineto L-cysteine, α-ketobutyrate and NH3. In the present study, we found that L-SeMet could be directly converted to CH3SeHusing purified homogenous human CGL instead of mouse liver cytosol. Authentic CH3SeH was prepared by reduction of dimethyldiselenidewith sodium tetrahydroborate. The gaseous product of the enzymatic reaction with L-SeMet was analyzed byGC/MS spectrometry. The GC/MS data was identical to that of authentic dinitrophenyl selenoether. We also analyzed thekinetic parameters for the formation of CH3SeH from L-SeMet by human and mouse CGL. These results suggest that humanCGL is a critical enzyme which is responsible for L-SeMet metabolism.
Abstract
Selenium is an essential trace element for mammals, but it is very toxic. Therefore, the control of selenium concentrationsshould be precisely and effectively monitored. Selenium is naturally obtained through foods and seleno-L-methionine (LSeMet)is a major form of selenium. It has been reported that L-SeMet is only converted into Se-adenosyl-L-SeMet. However,a recent study suggested that L-SeMet was directly metabolized into methylselenol (CH3SeH) in mouse liver extract by thereaction of cystathionine γ-lyase (CGL). The canonical reaction of CGL was known to catalyze the cleavage of L-cystathionineto L-cysteine, α-ketobutyrate and NH3. In the present study, we found that L-SeMet could be directly converted to CH3SeHusing purified homogenous human CGL instead of mouse liver cytosol. Authentic CH3SeH was prepared by reduction of dimethyldiselenidewith sodium tetrahydroborate. The gaseous product of the enzymatic reaction with L-SeMet was analyzed byGC/MS spectrometry. The GC/MS data was identical to that of authentic dinitrophenyl selenoether. We also analyzed thekinetic parameters for the formation of CH3SeH from L-SeMet by human and mouse CGL. These results suggest that humanCGL is a critical enzyme which is responsible for L-SeMet metabolism.
참고문헌 (28)
- Adams E, "Fluorometric determination of pyridoxal phosphate in enzymes", Methods Enzymol, 62, pp.407~410 (1979)
- Arthur JR, "Neometabolic roles for selenium", Proc. Nutr. Soc, 53, pp.615~624 (1994)
- Chen X, "Production of the neuromodulator H2S by cystathionine β-synthase via the condensation of cysteine and homocysteine", J. Biol. Chem, 279, pp.52082~52086 (2004)
- Esaki N, "Selenocysteine lyase, a novel enzyme that specifically acts on selenocysteine. Mammalian distribution and purification and properties of pig liver enzyme", J. Biol. Chem, 257, pp.4386~4391 (1982)
- Esaki N, "Enzymatic synthesis of selenocysteine in rat liver", Biochemistry, 20, pp.4492~4496 (1981)
- Ganther HE, "Selenium metabolism and mechanisms of cancer prevention", Adv. Exp. Med. Biol, 492, pp.119~130 (2001)
- Ganther HE, "Hydrogen selenide and methylselenol", Methods Enzymol, 143, pp.32~38 (1987)
- Ge K, "The epidemiology of selenium deficiency in the etiological study of endemic diseases in China", Am. J. Clin. Nutr. Supplement, 57, pp.259S~263S (1993)
- Hasegawa T, "Identification and metabolism of selenocysteine-glutathione selenenyl sulfide (CySeSG) in small intestine of mice orally exposed to selenocysteine", Arch. Toxicol, 71, pp.39~44 (1996)
- Heilman JM, "Transactivation of gene expression by NF-κB is dependent on thioredoxin reductase activity", Free Radic. Biol. Med, 51, pp.1533~1542 (2011)
- Ip C, "In vitro and in vivo studies of methylseleninic acid: evidence that a monomethylated selenium metabolite is critical for cancer chemoprevention", Cancer Res, 60, pp.2882~2886 (2000)
- 김경란, "새로운 신경전달물질 H2S 발생 효소, cystathionine γ-lyase의 대량발현 조건과 활성측정", 생명과학회지, 21(1), pp.119~126 (2011), 한국생명과학회
- Kobayashi Y, "Selenosugars are key and urinary metabolites for selenium excretion within the required to low-toxic range", Proc. Natl. Acad. Sci, 99, pp.15932~15936 (2002)
- Levander OA, "Trace elements in human and animal nutrition", pp.209~279 (1986), Academic Press Inc.
- HSe−, "FEBS Lett", 1991, 59~63
- Naganuma A, "Selenium efficiently depressed toxic side effect of cis-diamminedichloroplatinum", Res. Commun. Chem. Pathol. Pharmacol, 42, pp.127~134 (1993)
- Ogra Y, "Identification of a novel selenium metabolite, Se-methyl-Nacetylselenohexosamine, in rat urine by high-performance liquid chromatography--inductively coupled plasma mass spectrometry and--electrospray ionization tandem mass spectrometry", J. Chromatogr. B, 767, pp.301~312 (2002)
- Okuno T, "Purification and characterization of mouse hepatic enzyme that converts selenomethionine to methylselenol by it’s α, γ-elimination", Biol. Trace Elem. Res, 106, pp.77~94 (2005)
- Okuno T, "Identification of mouse selenomethionine α, γ-elimination enzyme", Biol. Trace Elem. Res, 108, pp.245~257 (2005)
- Okuno T, "Cystathionine γ-lyase contributes to selenomethionine detoxification and cytosolic glutathione peroxidase biosynthesis in mouse liver", Biol. Trace Elem. Res, 109, pp.155~171 (2006)
- Pascal TA, "Vitamin B6-responsive and-unresponsive cystathioninuria : two variant molecular forms", Science, 190, pp.1209~1211 (1975)
- Raymana MP, "Food-chain selenium and human health: spotlight on speciation", Brit. J. Nutr, 100, pp.238~253 (2008)
- Reeves MA, "The human selenoproteome:recent insights into functions and regulation", Cell Mol. Life Sci, 66, pp.2457~2478 (2009)
- Schrauzer GN, "The nutritional significance, metabolism and toxicology of selenomethionine", Adv. Food Nutr. Res, 47, pp.73~112 (2003)
- Sun Q, "Structural basis for the inhibition mechanism of human cystathionine gamma-lyase, an enzyme responsible for the production of H2S", J. Biol. Chem, 284, pp.3076~3085 (2009)
- Takahashi K, "Purification and characterization of human plasma glutathione peroxidase:a selenoglycoprotein distinct from the known cellular enzyme", Arch. Biochem. Biophys, 256, pp.677~686 (1987)
- Yarimizu J, "Efficiency of selenocysteine incorporation in human thioredoxin reductase", Antioxidants & Redox Signaling, 2, pp.643~651 (2000)
- Yasumoto K, "Identification of selenomethionine in soybean protein", J. Agric. Food Chem, 36, pp.463~467 (1988)