hydroxycitrate effects on tumor cells

Doug Skrecky (oberon@vcn.bc.ca)
Sun, 2 Aug 1998 04:57:37 -0700 (PDT)

Board M. Newsholme E.
Department of Biochemistry, University of Oxford, U.K. Title
Hydroxycitrate causes
altered pyruvate metabolism by tumorigenic cells. Source
Biochemistry & Molecular Biology International. 40(5):1047-56, 1996 Nov. 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.