title: Hydroxycitrate causes altered pyruvate metabolism by tumorigenic cells.
abstract: 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.
authors.affiliation: Department of Biochemistry, University of Oxford, U.K.
authors.forename: M
authors.initials: M
authors.lastname: Board
authors.forename: E
authors.initials: E
authors.lastname: Newsholme
mesh_terms: 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
chemical_list: 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