Metabolic consequences of pyruvate kinase inhibition by oxalate in intact rat hepatocytes.
The effects of oxalate on glycolysis and glucose production from trioses were studied in hepatocytes isolated from fed and fasted rats. 1--In cells from fed rats oxalate inhibited glycolysis at the pyruvate kinase step, as shown by an increased phosphoenolpyruvate concentration, a decreased lactate and pyruvate production and a reduction of the glycolytic flux estimated by the rate of detritiation of [6-3H] glucose. The plot of 1/lactate production versus oxalate concentration showed that pyruvate kinase is a limiting step of glycolysis and allowed to determine the apparent inhibition constant for oxalate: about 3035 microM which is near the physiological concentration of blood oxalate. Under conditions where both pyruvate kinase and glycolytic flux are inhibited, oxalate had no effect on the synthesis of [14C] glucose from [14C] triose. 2--In hepatocytes prepared from fasted rats and incubated with lactate and pyruvate, oxalate decreased gluconeogenesis. In cells isolated from fasted rats and incubated with dihydroxyacetone, oxalate decreased lactate and pyruvate production whereas glucose synthesis remained unchanged. It is concluded that the inhibition of pyruvate kinase cannot by itself increase the gluconeogenic flux from triose.
D000818:Animals; D005215:Fasting; D005260:Female; D005943:Gluconeogenesis / Q000187:drug effects; D006019:Glycolysis / Q000187:drug effects; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D010070:Oxalates / Q000494:pharmacology*; D019815:Oxalic Acid; D010728:Phosphoenolpyruvate / Q000378:metabolism; D011770:Pyruvate Kinase / Q000037:antagonists & inhibitors*; D011773:Pyruvates / Q000378:metabolism; D019289:Pyruvic Acid; D051381:Rats; D011919:Rats, Inbred Strains
D007773:Lactates; D010070:Oxalates; D011773:Pyruvates; D019344:Lactic Acid; D010728:Phosphoenolpyruvate; D019289:Pyruvic Acid; D019815:Oxalic Acid; D011770:Pyruvate Kinase