EFFECT OF BATHOCUPROINE DISULFONATE, A COPPER CHELATOR, ON CYST(E)INE METABOLISM BY FRESHLY ISOLATED RAT HEPATOCYTES
EFFECT OF BATHOCUPROINE DISULFONATE, A COPPER CHELATOR, ON CYST(E)INE METABOLISM BY FRESHLY ISOLATED RAT HEPATOCYTES
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DOI：
10.1152/ajpendo.1990.259.3.e443
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发表时间：
1990-09-01
影响因子：
--
通讯作者：
STIPANUK, MH
中科院分区：
文献类型：
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作者：
COLOSO, RM;DRAKE, MR;STIPANUK, MH
在新鲜分离的大鼠肝细胞中研究了L-半胱氨酸的代谢。由于半胱氨酸在中性pH的含氧孵育介质中快速氧化，因此研究了铜特异性螯合剂浴铜灵二磺酸盐的作用。添加浴铜灵二磺酸盐导致在与半胱氨酸孵育的肝细胞中细胞外半胱氨酸与半胱氨酸的比率更高。Bathocuproine disulfonate还增加了肝细胞对半胱氨酸加胱氨酸[cyst（e）ine]的总摄取和代谢，这与新鲜分离的大鼠肝细胞对半胱氨酸的转运比胱氨酸更有效一致。半胱氨酸在半胱氨酸亚磺酸依赖性和半胱氨酸亚磺酸非依赖性途径之间的分配也通过添加浴铜灵二磺酸盐而改变;导致牛磺酸加亚牛磺酸形成的总分解代谢通量的百分比更大，并且通过β-亚牛磺酸形成的总分解代谢通量的百分比更小。在由γ-氨基丁酸催化的反应中胱氨酸的裂解胱硫醚酶在含有浴铜灵二磺酸盐的孵育物中较少。因此，添加浴铜灵二磺酸盐以维持较高的细胞外巯基与二硫化物比率有利于大鼠肝细胞中半胱氨酸的半胱氨酸亚磺酸盐依赖性催化剂。
The metabolism of L-cysteine was studied in freshly isolated rat hepatocytes. Because cysteine is rapidly oxidized in oxygenated incubation medium at neutral pH, the effect of bathocuproine disulfonate, a copper-specific chelator, was investigated. Addition of bathocuproine disulfonate resulted in a higher extracellular cysteine-to-half-cystine ratio in incubations of hepatocytes with cysteine. Bathocuproine disulfonate also increased the total uptake and metabolism of cysteine plus cystine [cyst(e)ine] by hepatocytes, which is consistent with the more efficient transport of cysteine than of cystine by freshly isolated rat hepatocytes. The partitioning of cysteine between cysteinesulfinate-dependent and cysteinesulfinate-independent pathways of catabolism was also altered by the addition of bathocuproine disulfonate; the percentage of total catabolic flux that resulted in taurine plus hypotaurine formation was greater, and the percentage of total catabolic flux that occurred by the .beta.-cleavage of cystine in a reaction catalyzed by .gamma.-cystathionase was less in incubations that contained bathocuproine disulfonate. Thus addition of bathocuproine disulfonate to maintain a higher extracellular thiol-to-disulfide ratio favored cysteinesulfinate-dependent catabolism of cysteine in rat hepatocytes.