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Hydroxycitrate causes altered pyruvate metabolism by tumorigenic cells
1Department of Biochemistry, University of Oxford, U.K.
Biochemistry and Molecular Biology International
|November 1, 1996
Summary
Hydroxycitrate alters pyruvate metabolism in tumor cells, increasing oxidation and TCA cycle activity. Citrate becomes a significant pyruvate fate in these cells, unlike in normal cells where lactate is the primary product.
Area of Science:
- Biochemistry
- Cell Biology
- Cancer Metabolism
Background:
- Pyruvate is a central metabolite linking glycolysis and cellular respiration.
- Understanding pyruvate's metabolic fate is crucial for cancer research.
- Neoplastic cells exhibit altered metabolic pathways compared to normal cells.
Purpose of the Study:
- To investigate the metabolic fates of pyruvate in normal and neoplastic cells.
- To assess the impact of hydroxycitrate on pyruvate metabolism.
- To elucidate the role of citrate in tumor cell metabolism.
Main Methods:
- Isotope tracing using (3-(14)C-pyruvate) and (1-(14)C-pyruvate).
- Measurement of CO2 production from pyruvate oxidation.
- Quantification of citrate and lactate as pyruvate metabolites.
- Assessment of ATP-citrate lyase activity.
Main Results:
- Hydroxycitrate significantly reduced pyruvate consumption in tumor cells (72-85%) while increasing oxidation (75% to 91%).
- Tumorigenic cells showed higher ratios of TCA cycle to PDH activity, which were further elevated by hydroxycitrate.
- Citrate accounted for a substantial portion (14-37%) of glutaminolytic pyruvate in tumor cells, whereas glycolytic pyruvate was almost entirely converted to lactate.
Conclusions:
- Hydroxycitrate modulates pyruvate metabolism, favoring oxidation and TCA cycle activity in tumor cells.
- Citrate represents a major metabolic sink for glutaminolytic pyruvate in neoplastic cells.
- Distinct pyruvate metabolic fates characterize tumor cells compared to normal cells.