Hydroxycitrate causes altered pyruvate metabolism by tumorigenic cells.
Metabolic fates of pyruvate (CO2, lactate, citrate) in normal and neoplastic cells have been assessed. Pyruvate consumption by tumour cells falls (by 72-85%) and mean percentage oxidation rises from 75% to 91% with hydroxycitrate. Ratios of rates of oxidation of (3-(14)C-pyruvate) : (1-(14)C-pyruvate), indicating CO2 produced from TCA cycle activity : that from PDH activity, are higher for tumorigenic (0.17-0.24) than for non-tumorigenic (0.005-0.04) cells and increase (0.27-0.65 and 0.13-0.29, respectively) with hydroxycitrate. Although maximal ATP-citrate lyase activities do not correlate with malignancy, citrate may be a major fate of glutaminolytic pyruvate in tumour cells. Citrate accounts for 14-37% of consumed glutamine compared with 11-13% being recovered as CO2. By contrast, approximately 100% of glycolytic pyruvate is converted to lactate.
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Department of Biochemistry, University of Oxford, U.K.
Newsholme
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D001275:ATP Citrate (pro-S)-Lyase / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D002245:Carbon Dioxide / Q000378:metabolism; D002460:Cell Line; D002951:Citrates / Q000494:pharmacology*; D019343:Citric Acid / Q000378:metabolism; D002952:Citric Acid Cycle; D005947:Glucose / Q000378:metabolism; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism*; D010084:Oxidation-Reduction; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism; D019289:Pyruvic Acid / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D002951:Citrates; D011768:Pyruvate Dehydrogenase Complex; D002245:Carbon Dioxide; D019343:Citric Acid; D019344:Lactic Acid; D019289:Pyruvic Acid; C007999:hydroxycitric acid; D001275:ATP Citrate (pro-S)-Lyase; D005947:Glucose