THE PRODUCTION OF |14C| OXALATE DURING THE METABOLISM OF |14C| CARBOHYDRATES IN ISOLATED RAT HEPATOCYTES

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Abstract
Oxalate |14C| 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 glucose in the ratio 10: 4: 3: 1: 1. This difference between oxalate production from fructose and glucose was reflected in their rates of utilisation, glucose being poorly metabolised in hepatocytes from fasted rats. Fructose was rapidly metabolised, producing glucose, lactate and pyruvate as the major metabolites. Glycerol, xylitol and sorbitol were metabolised at half 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, however, 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: dihydroxyacetone phosphate ratios. The artificial electron acceptor, phenazine methosulphate (PMS) stimulated oxalate production from the polyols, particularly xylitol. In the presence of PMS, the order of oxalate production was fructose xylitol > glycerol > sorbitol in the ratio 10: 10: 6: 2. The 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. Oxalate |14C| 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. Whilst this labelling 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, particularly fructose, contribute to endogenous oxalate production lends support to the hypothesis that a high sucrose consumption contributes to the formation of renal oxalate stones in man.