Acetyl-CoA Synthetase 2, a Mitochondrial Matrix Enzyme Involved in the Oxidation of Acetate

Abstract

Using peptide sequences derived from bovine cardiac acetyl-CoA synthetase (AceCS), we isolated and characterized cDNAs for a bovine and murine cardiac enzyme designated AceCS2. We also isolated a murine cDNA encoding a hepatic type enzyme, designated AceCS1, identical to one reported recently (Luong, A., Hannah, V. C., Brown, M. S., and Goldstein, J. L. (2000) J. Biol. Chem. 275, 26458 -26466). Murine AceCS1 and AceCS2 were purified to homogeneity and characterized. Among C2-C5 short and medium chain fatty acids, both enzymes preferentially utilize acetate with similar affinity. The AceCS2 transcripts are expressed in a wide range of tissues, with the highest levels in heart, and are apparently absent from the liver. The levels of AceCS2 mRNA in skeletal muscle were increased markedly under ketogenic conditions. Subcellular fractionation revealed that AceCS2 is a mitochondrial matrix enzyme. [ 14 C]Acetate incorporation indicated that acetyl-CoAs produced by AceCS2 are utilized mainly for oxidation.

Direct noninvasive estimation of myocardial tricarboxylic acid cycle flux in vivo using hyperpolarized 13C magnetic resonance

“…We showed that it is possible to estimate myocardial V TCA in vivo through the time-resolved 13 C MRS measurement of [5][6][7][8][9][10][11][12][13] C]citrate following the injection of hyperpolarized [1-13 C]acetate. V TCA and the dynamics of 13 C citrate labeling were independent on the amount of injected substrate and did not correlate with the dynamics of 13 C acetylcarnitine labeling.…”

“…The signal decay of precursor and metabolites results from a combination of the effects of longitudinal relaxation (characterized by the time constant T 1 ), RF excitation, and biochemical conversion and all time courses were corrected for the effect of repeated RF excitations. The T 1 of [1-13 C]acetylcarnitine was set to 14.9 s, as previously determined in vivo [35], and that of [5][6][7][8][9][10][11][12][13] C]citrate to 20 s [46]. The acetate signal decay was treated as free parameter.…”

“…It is the shortest fatty acid and its uptake into the heart occurs through simple diffusion, its exchange between plasma and tissue only depending on the concentration gradient [5]. It is an effective oxidizable substrate formed endogenously that can be activated to acetylCoA via cytosolic or mitochondrial acetylCoA synthetase [6,7]. The cytosolic variant of acetylCoA synthetase is mainly present in the liver, while the mitochondrial variant is abundant in the heart and muscle and provides acetylCoA that is utilized mainly for oxidation under ketogenic conditions [7].…”

“…It is an effective oxidizable substrate formed endogenously that can be activated to acetylCoA via cytosolic or mitochondrial acetylCoA synthetase [6,7]. The cytosolic variant of acetylCoA synthetase is mainly present in the liver, while the mitochondrial variant is abundant in the heart and muscle and provides acetylCoA that is utilized mainly for oxidation under ketogenic conditions [7]. AcetylCoA enters the tricarboxylic acid (TCA) cycle as citrate via an irreversible condensation with oxaloacetate catalyzed by citrate synthase.…”

PET imaging with 11C-acetate in prostate cancer: a biochemical, radiochemical and clinical perspective

“…It produces acetyl-CoA, which is active only in fatty acid synthesis, is highly expressed in the liver and is regulated by the same factors and patterns as FAS [14]. The other (AceCS2) is an enzyme bound to the mitochondrial matrix, found abundantly in hearts and kidneys, and synthesising acetyl-CoA active in the TCA cycle and producing [ 14 C]CO 2 from [ 14 C]acetate [15].…”