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.