Disease relevance of Aacs

• Fatty acyl-CoAs of various chain lengths dose-dependently inhibited acetoacetyl-CoA synthetase from rat liver, but much less effectively a similar enzyme from a bacterium, Zoogloea ramigera I-16-M [1].

High impact information on Aacs

• The enzyme HMG-CoA reductase, beta-ketoacyl-CoA thiolase, acetoacetyl-CoA synthetase, and fatty acid synthase were not inhibited to any extent by this compound [2].
• The evidence suggests that the regulation of acetoacetyl-CoA synthetase activity and the utilization of acetoacetate for lipogenesis is closely linked to the regulation of cholesterogenesis [3].
• Acetoacetyl-CoA synthetase activity was depressed by feeding cholesterol or mevalonate administration and was enhanced by the addition to the diet of mevinolin and/or cholestyramine [3].
• These changes in activity of acetoacetyl-CoA synthetase were in synchrony with changes in the activities of 3-hydroxy-3-methylglutaryl-CoA synthase and 3-hydroxy-3-methylglutaryl-CoA reductase [3].
• Lastly, the liver microsomes had no detectable acetoacetyl-CoA synthetase or acetyl-CoA acetyltransferase activities [4].

Biological context of Aacs

• cDNA-derived amino acid sequence of acetoacetyl-CoA synthetase from rat liver [5].
• In order to examine the primary structure of acetoacetyl-CoA synthetase (acetoacetate-CoA ligase, EC 6.2.1.16; AA-CoA synthetase), the cDNA clone encoding this enzyme has been isolated from the cDNA library which was prepared from the liver of rat fed a diet supplemented with 4% cholestyramine and 0.4% pravastatin for 4 days [5].

Anatomical context of Aacs

• Acetoacetyl-CoA synthetase gene is abundant in rat adipose, and related with fatty acid synthesis in mature adipocytes [6].
• A preferential labeling of 3-beta-hydroxysterols over fatty acids was observed, which is consistent with the activation of acetoacetate in the cytosol by acetoacetyl-CoA synthetase [7].
• Conditions that decrease the citrate cleavage pathway of acetyl group translocation through the mitochondrial membrane are associated with an increase in carbon flux through acetoacetyl-CoA synthetase [7].
• Acetoacetyl-CoA synthetase activity was measured in human fibroblasts, 0.12 nmol min-1 mg cytosolic protein-1, and was found to be more than two orders of magnitude below the activity level of acetoacetyl-CoA synthetase in rat liver cytosol, 18.4 nmol min-1 mg cytosolic protein-1 [8].
• High labeling was observed in the midbrain, pons/medulla, cerebral cortex, hippocampus and cerebellum, and the localization profile of AACS mRNA was different from that of succinyl-CoA:3-oxoacid CoA-transferase (SCOT), a mitochondrial ketone body-activating enzyme [9].

Associations of Aacs with chemical compounds

• Acetoacetyl-CoA synthetase (AACS, acetoacetate-CoA ligase, EC 6.2.1.16) is a novel cytosolic ketone body (acetoacetate)-specific ligase, the physiological role of which remains to be elucidated [6].
• The regulation of acetoacetyl-CoA synthetase activity by modulators of cholesterol synthesis in vivo and the utilization of acetoacetate for cholesterogenesis [3].
• The activities surveyed include acetoacetyl-CoA hydrolase, acetoacetyl-glutathione hydrolase, acetoacetyl-CoA:glutathione acyl transferase, 3-ketothiolases I and II, 3-hydroxy-3-methylglutaryl-CoA lyase and synthase, and acetoacetyl-CoA synthetase [10].
• The activity of acetoacetyl-CoA synthetase in adrenals was enhanced by treatment of the animals with 4-aminopyrazolopyrimidine [3].
• Stimulation of hepatic cholesterol biosynthesis by fatty acids. Effects of oleate on cytoplasmic acetoacetyl-CoA thiolase, acetoacetyl-CoA synthetase and hydroxymethylglutaryl-CoA synthase [11].

Analytical, diagnostic and therapeutic context of Aacs

• Acetoacetyl-CoA synthetase (acetoacetate:CoA ligase) was purified to electrophoretic homogeneity from a rat liver supernatant by ammonium sulfate fractionation and successive chromatographies on DEAE-Sepharose, Blue-Sepharose, Red-Sepharose, CoA-Sepharose, Ultrogel AcA-44, and DEAE-Sepharose once again [12].
• In order to investigate the physiological role of AACS in the brain, we examined the localization of AACS mRNA in rat brain by in situ hybridization using a labeled probe [9].

References