Journal Article

Regulation of pyruvate metabolism and human disease

Taylor, Eric B., Tompkins, Sean C., Gray, Lawrence R.

2014

نظرة عامة

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.

• الناشر: Springer Basel,Springer Nature B.V
• موضوع: adenosine triphosphate / Biochemistry / Biomedical and Life Sciences / Biomedicine / Carbon / Carbon cycle / Cell Biology / Cellular biology / Citric acid / Citric Acid Cycle / Congestive heart failure / Cytoplasm / Cytosol - metabolism / Fluctuations / genes / Glycolysis / Heart Diseases - metabolism / heart failure / human diseases / human health / Humans / Life Sciences / Metabolism / Mitochondria / Mitochondria - metabolism / Models, Biological / mutation / Neoplasms - metabolism / Neurodegeneration / neurodegenerative diseases / Neurodegenerative Diseases - metabolism / Oxidative phosphorylation / Pathology / Phosphorylation / proteins / Pyruvate carboxylase / pyruvate dehydrogenase (lipoamide) / Pyruvate Metabolism, Inborn Errors - metabolism / Pyruvic acid / Pyruvic Acid - chemistry / Pyruvic Acid - metabolism / Review / Tricarboxylic acid cycle