Disease relevance of Acaca

• The heterozygous mutant mice (Acc1(+/-)) had normal fertility and lifespans and maintained a similar body weight to that of their wild-type cohorts [1].
• Acetyl-CoA carboxylase 2 mutant mice are protected against obesity and diabetes induced by high-fat/high-carbohydrate diets [2].
• The ability of gAd to increase GLUT4 myc translocation, glucose uptake, fatty acid uptake and oxidation, as well as AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) phosphorylation, was decreased by both hyperglycemia and hyperinsulinemia [3].

Psychiatry related information on Acaca

• Together these findings suggest that level of hypothalamic malonyl-CoA, which depends on the relative activities of acetyl-CoA carboxylase and FAS, is an indicator of energy status and mediates feeding behavior [4].
• The ACC activity was measured in the whole mouse brain of controls and after 1, 3, 6, 9, 12, and 24 h of food deprivation [5].

High impact information on Acaca

• We observed increased protein levels of the insulin receptor (4-fold) and uncoupling protein-3 (2-fold) in skeletal muscle and a significant increase in the phosphorylation of AMP-activated protein kinase and acetyl-CoA carboxylase [6].
• To determine whether epidermal fatty acid synthesis also is required for barrier homeostasis, we applied 5-(tetradecyloxy)-2-furancarboxylic acid (TOFA), an inhibitor of acetyl CoA carboxylase, after disruption of the barrier by acetone or tape stripping [7].
• The activities of NADP+-linked malate dehydrogenase, citrate lyase, acetyl-CoA carboxylase, and fatty acid synthetase, although lower in tumors than in normal glands, were not different in HD as compared to HI tumors [8].
• Deletion of fatty acid synthase or acetyl-CoA carboxylase (ACC) 1 in mice resulted in embryonic lethality, indicating that the de novo fatty acid synthesis is essential for embryonic development [9].
• Total ACC activity and malonyl-CoA levels were approximately 70-75% lower in liver of LACC1KO mice compared with that of the WT mice [9].

Chemical compound and disease context of Acaca

• After 1 h of food deprivation, the total ACC activity without citrate decreased to 0.575 +/- 0.087 fmol/min/mg and in the presence of citrate, 0.703 +/- 0.036 fmol/min/mg activity was measured [5].
• Changes of body weights and hepatic acetyl-CoA carboxylase activities were measured in voles and mice treated with monosodium-L-aspartate (MSA) [10].

Biological context of Acaca

• Physiologically, the level of hypothalamic malonyl-CoA appears to be determined through phosphorylation/dephosphorylation of ACC by AMP kinase in response to changes in the AMP/ATP ratio, an indicator of energy status [11].
• Acetyl-CoA carboxylase gene expression in the developing mouse brain. Comparison with other genes involved in lipid biosynthesis [12].
• It is shown that ACC and FAS mRNA levels are at a maximum 5 days after birth, a time when cell proliferation is intense in the mouse brain, and then decrease steadily to reach 20% of those maximal values at day 20 [12].
• We have recently demonstrated that carbohydrate responsive element-binding protein (ChREBP) plays a key role in the control of lipogenesis through the transcriptional regulation of lipogenic genes, including acetyl-CoA carboxylase and fatty acid synthase [13].
• A biotin analog inhibits acetyl-CoA carboxylase activity and adipogenesis [14].

Anatomical context of Acaca

• The ACC transcript isoforms, which were detected in the central nervous system (CNS), originated from promoter P2 of the ACC gene [12].
• The expression of acetyl-CoA carboxylase (ACC) in mouse peripheral nervous system (PNS) was investigated [15].
• Both ACC 265 and ACC 280 isoforms were expressed in the sciatic nerve, although ACC 265 was predominant [15].
• In addition, there was no difference in the acetate incorporation into fatty acids nor in the fatty acid oxidation between the hepatocytes of Acc1(+/-) mice and those of the wild type [1].
• In this study, we observed that treatment of 3T3-L1 cells with biotin chloroacetylated at the 1' nitrogen reduced the enzymatic activity of cytosolic acetyl-CoA carboxylase and concomitantly inhibited the differentiation of 3T3-L1 cells in a dose-dependent manner [14].

Associations of Acaca with chemical compounds

• They encode ACC enzymes which cannot be phosphorylated at the Ser-1200 locus, thus indicating that brain ACC is highly sensitive to citrate activation [12].
• In contrast, the expression and activity of acetyl-CoA carboxylase, which synthesizes malonyl-CoA and 5'-AMP-activated protein kinase, which regulates acetyl-CoA carboxylase, were not altered [16].
• Of the 2 CLA isomers, t10c12 caused a greater reduction in mammary ACC activity [17].
• Acetyl-CoA carboxylase beta expression mediated by MyoD and muscle regulatory factor 4 is differentially affected by retinoic acid receptor and retinoid X receptor [18].
• Glucose and fat metabolism in adipose tissue of acetyl-CoA carboxylase 2 knockout mice [19].
• There does not appear to be strict compartmentalization of malonyl-CoA from either of the ACC isozymes in the liver [20].

Enzymatic interactions of Acaca

• The steady-state level of malonyl-CoA is determined by its rate of synthesis catalysed by ACC (acetyl-CoA carboxylase) relative to its rate of turnover catalysed by FAS (fatty acid synthase) [21].
• We conclude that, although the metabolic adaptations to fasting and CR include changes in plasma leptin concentration and phosphorylated acetyl-CoA carboxylase, these effects occur without changes in AMPK activity [22].

Regulatory relationships of Acaca

• In this report, we present evidence that ob gene expression in cultured cells suppresses acetyl-CoA carboxylase gene expression and lipid synthesis which are induced by hormone treatment [23].
• A non-specific effect of the MEK inhibitors on AICAR accessibility to the oocyte was discounted by showing that they failed to suppress either nucleoside uptake or AICAR-stimulated phosphorylation of acetyl CoA carboxylase (ACC), a substrate of AMPK [24].

Other interactions of Acaca

• In fasted/refed animals, ACC and FAS mRNAs rose, but not to the same extent as in wild-type livers [25].
• Acetyl-CoA carboxylase and SREBP expression during peripheral nervous system myelination [15].
• In addition, ACC 265 mRNA and protein levels in the nerves of the trembler mutant, which is a mouse model of PNS dysmyelination, represented around 30% of the normal values [15].
• We found that hepatic mRNA levels of key lipogenic enzymes, acetyl-CoA carboxylase, fatty-acid synthase, and stearoyl-CoA desaturase-1 were increased in apoB/BATless mice compared with levels in apoB mice, suggesting increased lipogenesis in apoB/BATless mice [26].
• In contrast to Acc2(-/-) mice, Acc1(-/-) mice were not detected after mating [1].

Analytical, diagnostic and therapeutic context of Acaca

• Treatment of apoB/BATless mice for 4 weeks with intraperitoneal injections of a PPARgamma antisense oligonucleotide resulted in dramatic reductions of both PPARgamma1 and PPARgamma2 mRNA, PPARgamma2 protein, and mRNA levels of fatty-acid synthase and acetyl-CoA carboxylase [26].
• In maternal and fetal liver, acetyl-CoA carboxylase, pyruvate carboxylase, propionyl-CoA carboxylase, and beta-methylcrotonyl-CoA carboxylase abundances were determined by Western blotting; the content of mRNAs for most of these enzymes and holocarboxylase synthetase was determined by real-time RT-PCR [27].

References