Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2007 Jan;32(1):1-4.
doi: 10.1016/j.tibs.2006.11.002. Epub 2006 Dec 1.

Sirtuins: a conserved key unlocking AceCS activity

Brian J North  1 , David A Sinclair
Affiliations

Sirtuins: a conserved key unlocking AceCS activity

Brian J North et al. Trends Biochem Sci. 2007 Jan.

Abstract

Bacterial acetyl-coenzyme A (acetyl-CoA) synthetase (AceCS), an evolutionarily conserved enzyme that converts acetate to acetyl-CoA, is activated by sirtuin-mediated deacetylation. Two recent studies show that this mechanism of regulation is also crucial for mammalian AceCS activity, indicating that control of metabolism at the step of converting acetate to acetyl-CoA is conserved. These findings highlight a metabolic regulatory network controlled by sirtuins that has implications for the mechanisms of calorie restriction and modulation of mammalian lifespan.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Subcellular locations for sirtuin regulation of AceCS activity. In the mitochondria, SIRT3 can deacetylate and activate AceCS2, leading to the conversion of acetate to acetyl-CoA, which in turn can be shunted into the TCA cycle, resulting in an increase in ATP production. In the cytoplasm, SIRT1 deacetylates AceCS1 to convert acetate into acetyl-CoA for use in fatty acid synthesis. In addition, AceCS1 might be involved in recycling acetate from deacetylation reactions, which could take place in the cytoplasm where numerous proteins subjected to reversible acetylation are localized. SIRT4, an ADP-ribosyltransferase, inhibits glutamate dehydrogenase (GDH) activity through ribosylation, leading to an inhibition of amino-acid-stimulated insulin secretion (AASIS) in β cells and the induction of gluconeogenesis in the liver. Abbreviations: PAT, protein acetyltransferase; Nic, nicotinamide; AMP, adenosine monophosphate; Ac, acetylated lysine residue; ADPR, ADP-ribosylation; HAT, histone acetyltransferase; HDAC, histone deacetylase.
Figure 2
Figure 2
Model of the coordinated regulation of metabolic alteration during calorie restriction. Calorie restriction induces the activity of SIRT1 and SIRT3 but reduces that of SIRT4. Regulation by sirtuins effects a metabolic shift into gluconeogenesis through SIRT1 regulation of the transcriptional coactivator PGC1α, SIRT3 regulation of AceCS2, and SIRT4 regulation of glutamate dehydrogenase (GDH). In addition, SIRT1 regulation of AceCS1, leading to changes in fatty acid synthesis, and SIRT3 regulation of AceCS2, resulting in changes in gluconeogenesis, are consistent with metabolic changes that take place during calorie restriction. PDH, pyruvate dehydrogenase; UCP2, uncoupling protein 2.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Guarente L, Picard F. Calorie restriction – the SIR2 connection. Cell. 2005;120:473–482. - PubMed
    1. Lamming DW, et al. Small molecules that regulate lifespan: evidence for xenohormesis. Mol. Microbiol. 2004;53:1003–1009. - PubMed
    1. Dhahbi JM, et al. Calories and aging alter gene expression for gluconeogenic, glycolytic, and nitrogen-metabolizing enzymes. Am. J. Physiol. 1999;277:E352–E360. - PubMed
    1. Hagopian K, et al. Krebs cycle enzymes from livers of old mice are differentially regulated by caloric restriction. Exp. Gerontol. 2004;39:1145–1154. - PubMed
    1. Wolfe AJ. The acetate switch. Microbiol. Mol. Biol. Rev. 2005;69:12–50. - PMC - PubMed

Publication types

LinkOut - more resources