Acetyl-CoA and the Regulation of Metabolism: Mechanisms and Consequences
By Lei Shi, B. Tu. Current Opinion in Cell Biology, 2015
792 citations recorded by the source corpus.
Acetyl-CoA represents a key node in metabolism due to its intersection with many metabolic pathways and transformations. Emerging evidence reveals that cells monitor the levels of acetyl-CoA as a key indicator of their metabolic state, through distinctive protein acetylation modifications dependent on this metabolite. We offer the following conceptual model for understanding the role of this sentinel metabolite in metabolic regulation. High nucleocytosolic acetyl-CoA amounts are a signature of a “growth” or “fed” state and promote its utilization for lipid synthesis and histone acetylation. In contrast, under “survival” or “fasted” states, acetyl-CoA is preferentially directed into the mitochondria to promote mitochondrial-dependent activities such as the synthesis of ATP and ketone bodies. Fluctuations in acetyl-CoA within these subcellular compartments enable the substrate-level regulation of acetylation modifications, but also necessitates the function of sirtuin deacetylases to catalyze removal of spontaneous modifications that might be unintended. Thus, understanding the sources, fates, and consequences of acetyl-CoA as a carrier of two-carbon units has started to reveal its underappreciated but profound influence on the regulation of numerous life processes.
Subfields: Cancer Research, Geriatrics and Gerontology, Physiology
View Paper: https://www.semanticscholar.org/paper/51c4ddd3d1d6bca479f025d52451f10cc9fd3247
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In Cancer Research
In Geriatrics and Gerontology
In Physiology
Citations in the corpus
- Unraveling the Complex Interplay Between T Cell Metabolism and Function (2018, background): “Acetyl-CoA generated from pyruvate is oxidized in the mitochondria for energy but also contributes to a range of other cellular processes, including acetylation of proteins and histones (76).”
- Acetyl coenzyme A: a central metabolite and second messenger. (2015, background): “As thioester bonds are energy rich, the chemical structure of acetyl-CoA facilitates the transfer of the acetyl moiety to a variety of acceptormolecules, including amino groups on proteins (Shi and Tu, 2015).”