THE PRODUCTION OF [C-14] OXALATE DURING THE METABOLISM OF [C-14] CARBOHYDRATES IN ISOLATED RAT HEPATOCYTES
THE PRODUCTION OF [C-14] OXALATE DURING THE METABOLISM OF [C-14] CARBOHYDRATES IN ISOLATED RAT HEPATOCYTES
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DOI：
10.1038/icb.1980.10
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发表时间：
1980-01-01
期刊：
影响因子：
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通讯作者：
CONYERS, RAJ
中科院分区：
文献类型：
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作者：
ROFE, AM;JAMES, HM;CONYERS, RAJ
正常大鼠肝细胞在U-14C碳水化合物代谢过程中产生14c -草酸盐。在10 mM时，草酸酯的生成顺序为果糖、甘油、木糖醇、山梨糖醇。葡萄糖的比例是10:4:3:1:1。果糖和葡萄糖产生草酸的差异反映在它们的利用率上，葡萄糖在禁食大鼠的肝细胞中代谢不良。果糖代谢迅速，主要代谢产物为葡萄糖、乳酸和丙酮酸。甘油、木糖醇和山梨醇的代谢速率是果糖的1/2，主要代谢产物是葡萄糖、乳酸和甘油磷酸盐。这些多元醇产生的中间代谢物模式的显著相似性并没有反映在草酸盐的产生速率上。肝多元醇代谢导致细胞质内NADH水平升高，乳酸：丙酮酸和甘油：磷酸二氢丙酮比值升高表明了这一点。人工电子受体苯那嗪甲硫代硫酸盐（PMS）刺激多元醇，特别是木糖醇产生草酸盐。在PMS作用下，草酸酯的生成顺序为果糖-葡萄糖-葡萄糖。木糖醇>甘油>山梨糖醇的比例为10:10:6:2。PMS还刺激了多元醇中葡萄糖、乳酸和丙酮酸的产生，而果糖的一般代谢，包括草酸的产生，几乎没有受到影响。14c -草酸盐是由1-14C、2-14C和6-14C产生的，而不是由3,4- 14c葡萄糖产生的。虽然这种标记模式与多种途径产生草酸是一致的，但这表明，通过羟丙酮酸代谢是各种碳水化合物产生草酸的主要途径，木糖醇可能是例外，木糖醇似乎有另一种草酸产生机制。观察到碳水化合物，特别是果糖，有助于内源性草酸的产生，这支持了高蔗糖消耗有助于人体肾草酸结石形成的假设。
14C-Oxalate was produced during the metabolism of U-14C carbohydrates in hepatocytes isolated from normal rats. At 10 mM the order of oxalate production was fructose > glycerol > xylitol > sorbitol .gtoreq. glucose in the ratio 10:4:3:1:1. This difference between oxalate production from fructose and glucose was reflected in their rates of utilization, glucose being poorly metabolized in hepatocytes from fasted rats. Fructose was rapidly metabolized, producing glucose, lactate and pyruvate as the major metabolites. Glycerol, xylitol and sorbitol were metabolized at 1/2 the rate of fructose, the major metabolites being glucose, lactate and glycerophosphate. The marked similarity in the pattern of intermediary metabolites produced by these polyols was not reflected in the rates of oxalate production. Hepatic polyol metabolism resulted in high levels of cytosolic NADH, as indicated by elevated lactate:pyruvate and glycerophosphate:dihydroacetone phosphate ratios. The artificial electron acceptor, phenazine methosulfate (PMS) stimulated oxalate production from the polyols, particularly xylitol. In the presence of PMS the order of oxalate production was fructose .gtoreq. xylitol > glycerol > sorbitol in the ratio 10:10:6:2. Production of glucose, lactate and pyruvate from the polyols was also stimulated by PMS, whereas the general metabolism of fructose, including oxalate production, was little affected. 14C-Oxalate was produced from 1-14C, 2-14C and 6-14C but not 3,4-14C glucose in hepatocytes isolated from non-fasted, pyridoxine-deficient rats. While this labeling pattern is consistent with oxalate being produced by a number of pathways, it is suggested that metabolism via hydroxypyruvate is a major route for oxalate production from various carbohydrates, with perhaps the exception of xylitol, which appears to have an alternative mechanism for oxalate production. The observation that carbohydrates, particulary fructose, contribute to endogenous oxalate production lends support to the hypothesis that high sucrose consumption contributes to the formation of renal oxalate stones in humans.