Premium
Hydroxycitrate causes altered pyruvate metabolism by tumorigenic cells
Author(s) -
Board Mary,
Newsholme Eric
Publication year - 1996
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1080/15216549600201683
Subject(s) - citric acid cycle , glycolysis , pyruvate decarboxylation , glutamine , biochemistry , pyruvate carboxylase , metabolism , chemistry , pyruvate dehydrogenase complex , pyruvic acid , biology , enzyme , amino acid
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 (3‐14C‐pyruvate): (1‐14C‐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, ≈100% of glycolytic pyruvate is converted to lactate.