Acetyl-CoA and the regulation of metabolism: mechanisms and consequences

Abstract

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.

Reduced Histone Expression or a Defect in Chromatin Assembly Induces Respiration

“…On the other hand, histone acetylation and chromatin structure regulate the expression of metabolic genes (28,29). In this study, we demonstrate that a decreased expression of histones or altered nucleosome structure of chromatin in budding yeast results in the upregulation of mitochondrial activity, redirection of metabolism from fermentation to respiration, and significantly increased ATP synthesis.…”

Metformin targets histone acetylation in cancer-prone epithelial cells

“…The finding that histone acetylation changes following the metabolic stress imposed by metformin supports the notion that directing metabolism to modulate the epigenetic landscape is a promising therapeutic strategy for the management of aging-driven diseases including cancer. Metformin's ability to regulate mitonuclear communication 64 and metabolically modulate the epigenetic landscape should guide the development of new therapeutic strategies involving metabolo-epigenetic aging/cancer prevention and therapy.…”

Synthesis of Poly-(R-hydroxyalkanoates) byCupriavidus necatorATCC 17699 Using Mexican Avocado(Persea americana)Oil as a Carbon Source

“…Besides the C=O group, an asymmetrical C-H bending vibration in CH 3 group shows an absorption band at 1453 cm −1 , whereas C-O-H bond shows a peak at 1378 [36]. Other peaks were recorded in the 1100 to 1290 cm −1 region; bands found around 1176, 1221, and 1270 cm −1 were attributed to polymer crystalline structures, and their presence was related to the C-O-C functional group [24].…”

“…By contrast, noncarbon nutrient limitation leads to inhibition of the central enzymes of the tricarboxylic cycle (TCA cycle). Consequently, the acetylCoA is channelled towards the PHA synthesis [23][24][25], as depicted in Figure 1.…”

“…The PHA synthesis in C. necator is highly associated with growth conditions and is mediated by the acetyl-CoA precursor [23,24]. In balanced nutritional environments, fatty acids provide precursors, free energy, and cofactors for cell growth and maintenance and for macromolecular synthesis.…”