Citrate Metabolism in Prostate and Other Cancers
The Metabolic Roles of Citrate in Normal Mammalian Cells
Citrate occupies a critical crossroad step in the intermediary metabolism of most normal mammalian cells (Fig. 1). It is synthesized in the mitochondria, where it becomes the entry oxidative substrate into the Krebs cycle. As such, its oxidation provides the major source of cellular ATP production. Because citrate is the common intermediate that results from glucose and fatty acid utilization, it is the link for their complete oxidation. This is the bioenergetic role of citrate that is most commonly considered to be the major relationship of citrate in cellular intermediary metabolism. However citrate serves other important metabolic roles. By virtue of its oxidation via the Krebs cycle, it provides several intermediates that couples the Krebs cycle with other associated synthetic and catabolic pathways of metabolism. For example, its oxidation to alpha ketoglutarate can be coupled by aminotransferases for the synthesis of amino...
KeywordsProstate Cell Prostatic Fluid Normal Prostate Epithelial Cell Normal Mammalian Cell Citrate Metabolism
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
Acknowledgment The studies of LCC and RBF described in this review were supported in part by NIH grants CA71207, CA21097, CA79903, and CA93443.
- Harkonen, P. L. 1981. Androgenic control of glycolysis, the pentose cycle and pyruvate dehydrogenase in the rat ventral prostate. J Steroid Biochem Mol Biol 14:1075–1084.Google Scholar
- Huggins, C. 1947. The prostatic secretion. Harvey Lect 42:148–193.Google Scholar
- Kline, E. E., Treat, E. G., Averna, T. A., Davis, M. S., Smith, A. Y., and Sillerud, L. O. 2006. Citrate concentrations in human seminal fluid and expressed prostatic fluid determined via 1H nuclear magnetic resonance spectroscopy outperform prostate specific antigen in prostate cancer detection. J Urol 176:2274–2279.CrossRefPubMedGoogle Scholar
- Parlo, R. A., and Coleman, P. S. 1984. Enhanced rate of citrate export from cholesterol-rich hepatoma mitochondria. J Biol Chem 259:997–10003.Google Scholar
- Parlo, R. A., and Coleman, P. S. 1986. Continuous pyruvate carbon flux to newly synthesized cholesterol and the suppressed evolution of pyruvate-generated CO2. in tumors: Further evidence for a persistent truncated Krebs cycle in hepatomas Biochim Biophys Acta 886:169–176.CrossRefPubMedGoogle Scholar
© Springer Science + Business Media, LLC 2009