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成年人体内静脉输注谷胱甘肽后血浆蛋氨酸和半胱氨酸的动力学变化

Plasma methionine and cysteine kinetics in response to an intravenous glutathione infusion in adult humans.

作者信息

Fukagawa N K, Ajami A M, Young V R

机构信息

Clinical Research Center, Rockefeller University, New York, New York 10021, USA.

出版信息

Am J Physiol. 1996 Feb;270(2 Pt 1):E209-14. doi: 10.1152/ajpendo.1996.270.2.E209.

DOI:10.1152/ajpendo.1996.270.2.E209
PMID:8779940
Abstract

Glutathione (GSH), a tripeptide (gamma-glutamyl-cysteinyl-glycine), is thought to be both a storage and a transport form of cysteine (Cys). In a previous study (T. Hiramatsu, N.K. Fukagawa, J.S. Marchini, J. Cortiella, Y.-M. Yu, T.E. Chapman, and V.R. Young. Am. J. Clin. Nutr. 60: 525-533, 1994), the direct tracer-derived estimate of Cys flux was considerably higher than that predicted from estimates of protein turnover. To further examine the components of plasma Cys flux, seven normal-weight healthy adult men and women (26 +/- 2 yr) received stable isotope tracer infusions of L-[methyl-2H3;1-13C]methionine, L-[3,3-2H2]cysteine, and L-[methyl-2H3]leucine for 460 min. After a 3-h baseline period, GSH was administered at approximately 32 mumol.kg-1.h-1 until the end of the study. Expired breath and blood samples were obtained at timed intervals and analyzed for isotope enrichment using mass spectrometry. Leucine, alpha-ketoisocaproate, and methionine (carboxyl carbon, methyl moiety, remethylation, and transsulfuration) turnover were reduced during GSH administration (P < 0.01). In the final hour of GSH administration, Cys flux increased by 61% from 55.1 +/- 1.7 to 88.7 +/- 5.2 mumol.kg-1.h-1 (P < 0.01), which was essentially equivalent to the rate of exogenous GSH infusion. These data suggest that GSH breakdown accounts for approximately 50% of tracer-derived Cys flux basally and for all of the increase in measured Cys turnover during exogenous GSH infusion.

摘要

谷胱甘肽(GSH)是一种三肽(γ-谷氨酰-半胱氨酰-甘氨酸),被认为是半胱氨酸(Cys)的一种储存和运输形式。在之前的一项研究中(T. Hiramatsu、N.K. Fukagawa、J.S. Marchini、J. Cortiella、Y.-M. Yu、T.E. Chapman和V.R. Young。《美国临床营养学杂志》60: 525 - 533, 1994),通过示踪剂直接得出的Cys通量估计值远高于根据蛋白质周转率估计值所预测的结果。为了进一步研究血浆Cys通量的组成部分,7名体重正常的健康成年男性和女性(26±2岁)接受了L-[甲基-2H3;1-13C]蛋氨酸、L-[3,3-2H2]半胱氨酸和L-[甲基-2H3]亮氨酸的稳定同位素示踪剂输注,持续460分钟。在3小时的基线期后,以约32 μmol·kg-1·h-1的剂量给予GSH,直至研究结束。定时采集呼出气体和血液样本,并用质谱法分析同位素富集情况。在给予GSH期间,亮氨酸、α-酮异己酸和蛋氨酸(羧基碳、甲基部分、再甲基化和转硫作用)的周转率降低(P < 0.01)。在给予GSH的最后一小时,Cys通量从55.1±1.7增加到88.7±5.2 μmol·kg-1·h-1,增幅为61%(P < 0.01),这基本上等同于外源性GSH的输注速率。这些数据表明GSH分解在基础状态下约占示踪剂衍生Cys通量的50%,并且在外源性GSH输注期间所测量的Cys周转率的全部增加均由其导致。

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