FORMATION OF THE L-CYSTEINE-GLYOXYLATE ADDUCT IS THE MECHANISM BY WHICH L-CYSTEINE DECREASES OXALATE PRODUCTION FROM GLYCOLATE IN RAT HEPATOCYTES

被引:16
作者
BAKER, PW [1 ]
BAIS, R [1 ]
ROFE, AM [1 ]
机构
[1] INST MED & VET SCI,DIV CLIN BIOCHEM,ADELAIDE,SA 5000,AUSTRALIA
关键词
D O I
10.1042/bj3020753
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Formation of thiazolidine-2,4-dicarboxylic acid, the L-cysteine-glyoxylate adduct, is the putative mechanism by which L-cysteine reduces hepatic oxalate production from glycollate [Bais, Rofe and Conyers (1991) J. Urol. 145, 1302-1305]. This was investigated in isolated rat hepatocytes by the simultaneous measurement of both adduct and oxalate formation. Different diastereoisomeric ratios of cis- and trans-adduct were prepared and characterized to provide both standard material for the enzymic analysis of adduct in hepatocyte supernatants and to investigate the stability and configuration of the adduct under physiological conditions. In the absence of L-cysteine, hepatocytes produced oxalate from 2 mM glycollate at a rate of 822+/-42 nmol/30 minper 10(7) cells. The addition of L-cysteine to the incubation medium at 1.0, 2.5 and 5.0 mM lowered oxalate production by 14+/-2, 25+/-3 (P < 0.05) and 38+/-3% (P < 0.01) respectively. These reductions were accompanied by almost stoichiometric increases in the levels of the adduct: 162+/-6, 264+/-27 and 363+/-30 nmol/30 min per 10(7) cells. Adduct formation is therefore confirmed as the primary mechanism by which L-cysteine decreases oxalate production from glycollate. As urinary oxalate excretion is a prime risk factor in the formation of calcium oxalate stones, any reduction in endogenous oxalate production is of clinical significance in the prevention of this formation.
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页码:753 / 757
页数:5
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