Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:6.2.1.1 (ACS)
78,556 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The mean volume of adipocytes, the rates of fatty acid and acylglycerol glycerol synthesis from various precursors (in vitro), the rates of oxidation of acetate and glucose (in vitro) and the activities of lipoprotein lipase and various lipogenic enzymes were determined for perirenal adipose tissue from foetal lambs during the last month of gestation. 2. The fall in the rate of growth of perirenal adipose tissue during the last month of gestation is associated with a diminished capacity for fatty acid synthesis and lipoprotein lipase activity, but no change in the rate of acylglycerol glycerol synthesis was observed. There was no fall in the activities of cytosolic acetyl-CoA synthetase or the NADP-linked dehydrogenases, suggesting that the decrease in the rate of fatty acid synthesis was due to an impairment at the level of acetyl-CoA carboxylase or fatty acid synthetase. 3. The rate of fatty acid synthesis from acetate was greater than that from glucose. The rate of fatty acid synthesis from glucose per adipocyte of foetal lambs was similar to that of young sheep. The characteristic metabolism of adipose tissue of the adult sheep is thus present in the foetus, despite the relatively large amounts of glucose in the foetal 'diet'.
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PMID:Aspects of adipose-tissue metabolism in foetal lambs. 703 12

Several reports have suggested that the reduction of intra-abdominal visceral fat after physical exercise is more prominent than that of subcutaneous fat. We compared some parameters in mesenteric and subcutaneous fats between sedentary and exercised rats (treadmill running; 10-20 m/min, 60 min/day, 7 days). Tissue weight and cell volume were decreased in mesenteric fat by the exercise. The exercise reduced activity and mRNA levels of acyl-CoA synthetase (ACS; 67 and 26% of those of the sedentary group, respectively), mRNA levels of lipoprotein lipase (LPL; 49% of those of the sedentary group), and GLUT-4 (38% of those of the sedentary group) in the mesenteric fat. In contrast, all of these parameters did not change significantly in the subcutaneous fat. Gastrocnemius muscle was heavier in exercised rats. ACS activity was elevated in the gastrocnemius muscle of the exercised rats (137% of those of sedentary group), although mRNA levels of ACS, LPL, and GLUT-4 did not change in the muscle by the exercise. These observations suggest that mesenteric fat may contribute to switching of distribution of plasma energy flux, including lipid and glucose, from fat tissue to muscle in physical exercise.
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PMID:Marked reduction of acyl-CoA synthetase activity and mRNA in intra-abdominal visceral fat by physical exercise. 833 53

Significant hypolipidemic activity was demonstrated by 6-ethoxycarbonyl-1-3-phenyl-1,3,5-triazabicyclo[3.1.0]hexane-2,4-dione, 2-ethoxycarbonyl-5-phenyl-1,3,5-triazine-4,6(1H,5H)-dione and 2-ethoxycarbonyl-5-(4-chlorophenyl)-1,3,5-triazine-4,6(1H,5H)-dione in rodents at 20 mg/kg/day. These agents lowered serum cholesterol and triglyceride levels by approximately 40% in mice after 16 d. Tissue lipids in rat liver, small intestinal mucosa, aortic wall and feces were reduced by treatment with the agents. Very low density lipoprotein (VLDL) and low density lipoprotein (LDL) cholesterol levels were reduced in the rat; high density lipoprotein (HDL) cholesterol levels were elevated after 14 d of treatment. The activities of regulatory enzymes, e.g., acetyl-CoA synthetase, acyl-CoA:cholesterol acyltransferase, cholesterol 7 alpha-hydroxylase, sn-glycerol-3-phosphate acyltransferase, phosphatidylate phosphohydrolase and heparin-induced lipoprotein lipase, involved in de novo synthesis of hepatic lipids were affected by the agents. The new compounds may represent another class of potentially useful hypolipidemic agents for the treatment of atherosclerosis since HDL cholesterol levels were increased and VLDL and LDL cholesterol levels were lowered by some of the agents.
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PMID:Hypolipidemic activity of 6-alkoxycarbonyl-3-aryl-1,3,5- triazabicyclo[3.1.0]hexane-2,4-diones and 2-alkoxycarbonyl-5-aryl-1,3,5-triazine-4,6(1H,5H)-diones in rodents. 846 53

The VLDL (very low-density lipoprotein) receptor is a peripheral lipoprotein receptor expressing in fatty acid active tissues abundantly. In the Balb/c fasting mice, VLDL receptor as well as LPL (lipoprotein lipase), FAT (fatty acid translocase)/CD36, H-FABP (heart-type fatty acid-binding protein), ACS (acyl-CoA synthetase) and LCAD (long-chain acyl-CoA dehydrogenase) expressions increased. An electron microscopic examination indicated the lipid droplets that accumulated in the hearts of fasting Balb/c mice. During the development of SD (Sprague-Dawley) rats, VLDL receptor, LPL, FAT/CD36, H-FABP, ACS, and LCAD mRNAs concomitantly increased with growth. However, PK (pyruvate kinase) mRNA expression was negligible. In cultured neonatal rat cardiomyocytes, VLDL receptor expression increased with days in culture. Oil red-O staining showed that cardiomyocytes after 7 days in culture (when the VLDL receptor protein is present) accumulated beta-migrating VLDL. Thereby, we showed that the cardiac VLDL receptor pathway for delivery of remnant lipoprotein particles might be part of a cardiac fatty acid metabolism.
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PMID:Remnant lipoprotein particles are taken up into myocardium through VLDL receptor--a possible mechanism for cardiac fatty acid metabolism. 1205 60

Screening of a small set of nonselective lipase inhibitors against endothelial lipase (EL) identified a potent and reversible inhibitor, N-(3-(3,4-dichlorophenyl)propyl)-3-hydroxy-1-methyl-2-oxo-1,2-dihydropyridine-4-carboxamide (5; EL IC₅₀ = 61 nM, EL_HDL IC₅₀ = 454 nM). Deck mining identified a related hit, N-(3-(3,4-dichlorophenyl)propyl)-4-hydroxy-1-methyl-5-oxo-2,5-dihydro-1H-pyrrole-3-carboxamide (6a; EL IC₅₀ = 41 nM, EL_HDL IC₅₀ = 1760 nM). Both compounds were selective against lipoprotein lipase (LPL) but nonselective versus hepatic lipase (HL). Optimization of compound 6a for EL inhibition using HDL as substrate led to N-(4-(3,4-dichlorophenyl)butan-2-yl)-1-ethyl-4-hydroxy-5-oxo-2,5-dihydro-1H-pyrrole-3-carboxamide (7c; EL IC₅₀ = 148 nM, EL_HDL IC₅₀ = 218 nM) having improved PK over compound 6a, providing a tool molecule to test for the ability to increase HDL-cholesterol (HDL-C) levels in vivo using a reversible EL inhibitor. Compound 7c did not increase HDL-C in vivo despite achieving plasma exposures targeted on the basis of enzyme activity and protein binding demonstrating the need to develop more physiologically relevant in vitro assays to guide compound progression for in vivo evaluation.
ACS Med Chem Lett 2018 Jul 12
PMID:PK/PD Disconnect Observed with a Reversible Endothelial Lipase Inhibitor. 3003 99

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