Regulation and function of the mammalian tricarboxylic acid cycle Review
| Authors: | Arnold, P. K.; Finley, L. W. S. |
| Review Title: | Regulation and function of the mammalian tricarboxylic acid cycle |
| Abstract: | The tricarboxylic acid (TCA) cycle, otherwise known as the Krebs cycle, is a central metabolic pathway that performs the essential function of oxidizing nutrients to support cellular bioenergetics. More recently, it has become evident that TCA cycle behavior is dynamic, and products of the TCA cycle can be co-opted in cancer and other pathologic states. In this review, we revisit the TCA cycle, including its potential origins and the history of its discovery. We provide a detailed accounting of the requirements for sustained TCA cycle function and the critical regulatory nodes that can stimulate or constrain TCA cycle activity. We also discuss recent advances in our understanding of the flexibility of TCA cycle wiring and the increasingly appreciated heterogeneity in TCA cycle activity exhibited by mammalian cells. Deeper insight into how the TCA cycle can be differentially regulated and, consequently, configured in different contexts will shed light on how this pathway is primed to meet the requirements of distinct mammalian cell states. © 2022 The Authors |
| Keywords: | protein expression; review; nonhuman; protein function; protein localization; cell proliferation; animal; metabolism; animals; gene expression; cell fate; enzyme activity; physiology; stem cell; biosynthesis; molecular evolution; regulatory mechanism; mammal; paracrine signaling; lactate dehydrogenase; mammals; biochemistry; fatty acid; cell metabolism; energy metabolism; oxidation; glycolysis; oxidative phosphorylation; immunocompetent cell; glutamine; mammal cell; allosterism; catabolism; citric acid cycle; 2 oxoglutaric acid; krebs cycle; metabolic pathways; fatty acid oxidation; mammalian cells; acetyl coenzyme a; bioenergetics; histone acetylation; succinic acid; human; cell state; physiological process; glyceraldehyde 3 phosphate; malignant neoplasm; tricarboxylic acid cycle; glycerophosphate; pyruvate carboxylase; cellulars; bioenergetic |
| Journal Title: | Journal of Biological Chemistry |
| Volume: | 299 |
| Issue: | 2 |
| ISSN: | 0021-9258 |
| Publisher: | American Society for Biochemistry and Molecular Biology |
| Date Published: | 2023-02-01 |
| Start Page: | 102838 |
| Language: | English |
| DOI: | 10.1016/j.jbc.2022.102838 |
| PUBMED: | 36581208 |
| PROVIDER: | scopus |
| PMCID: | PMC9871338 |
| DOI/URL: | |
| Notes: | Review -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- MSK corresponding author is Lydia Finley -- Export Date: 1 March 2023 -- Source: Scopus |
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