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Cell Mol Life Sci. 2014 Jul;71(14):2577-604. doi: 10.1007/s00018-013-1539-2. Epub 2013 Dec 21.

Regulation of pyruvate metabolism and human disease.

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Department of Biochemistry, Fraternal Order of the Eagles Diabetes Research Center, and François M. Abboud Cardiovascular Research Center, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, 51 Newton Rd, 4-403 BSB, Iowa City, IA, 52242, USA.


Pyruvate is a keystone molecule critical for numerous aspects of eukaryotic and human metabolism. Pyruvate is the end-product of glycolysis, is derived from additional sources in the cellular cytoplasm, and is ultimately destined for transport into mitochondria as a master fuel input undergirding citric acid cycle carbon flux. In mitochondria, pyruvate drives ATP production by oxidative phosphorylation and multiple biosynthetic pathways intersecting the citric acid cycle. Mitochondrial pyruvate metabolism is regulated by many enzymes, including the recently discovered mitochondria pyruvate carrier, pyruvate dehydrogenase, and pyruvate carboxylase, to modulate overall pyruvate carbon flux. Mutations in any of the genes encoding for proteins regulating pyruvate metabolism may lead to disease. Numerous cases have been described. Aberrant pyruvate metabolism plays an especially prominent role in cancer, heart failure, and neurodegeneration. Because most major diseases involve aberrant metabolism, understanding and exploiting pyruvate carbon flux may yield novel treatments that enhance human health.

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