Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.3.99.3 (acyl-CoA dehydrogenase)
 1,425 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The 3-thia fatty acid tetradecylthioacetic acid (TTA) has recently been shown to inhibit growth rate and increase peroxisomal acyl-CoA oxidase (ACO) (EC 1.3.99.3) activity in the Morris 7800 C1 hepatoma cells. Dexamethasone potentiates and insulin antagonizes these effects of TTA. We demonstrate here the metabolism of the 3-thia acids in these cells and the influence of insulin and dexamethasone on this. (1) The Morris 7800 C1 hepatoma cells exhibited a low omega-hydroxylation activity of the 3-thia acid (and lauric acid). The combination of TTA and dexamethasone induced the omega-hydroxylation and ACO activities in these cells. TTA alone induced ACO activity, but not omega-hydroxylation activity. Insulin counteracted the induction of both enzyme activities. These results indicate that these two enzyme activities are under similar but independent regulation. (2) Hepatoma cells grown with 80 microM TTA in the medium accumulated phospholipids containing the 3-thia fatty acid. After 7 days, TTA accounted for approx. 40% of the total fatty acids in the phospholipids. In addition, TTA affected the incorporation of endogenous fatty acids into phospholipids by decreasing the amounts of palmitic (C16:0) and vaccenic (C18:1(n-7)) acid and increasing the amounts of linoleic (C18:2(n-6)) and alpha-linolenic (C18:3(n-3)) acid in the phospholipids. (3) Dexamethasone increased the incorporation of labelled TTA into both phospholipids and triacylglycerol. Most of the labelled triacylglycerol formed was secreted into the medium. Insulin increased the incorporation of labelled TTA into triacylglycerol, but not into phospholipids. The labelled triacylglycerol formed was retained in the cells.
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PMID:Hormonal and substrate regulation of 3-thia fatty acid metabolism in Morris 7800 C1 hepatoma cells. 837 45

Insulin-regulated aminopeptidase (IRAP, also termed vp165) is known to be localized on the GLUT4-containing vesicles and to be recruited to the plasma membrane after stimulation with insulin. The cytoplasmic region of IRAP contains two dileucine motifs and acidic regions, one of which (amino acid residues 55-82) is reportedly involved in retention of GLUT4-containing vesicles. The region of IRAP fused with glutathione-S-transferase [GST-IRAP(55-82)] was incubated with lysates from 3T3-L1 adipocytes, leading to identification of long-chain, medium-chain, and short-chain acyl-coenzyme A dehydrogenases (ACDs) as the proteins associated with IRAP. The association was nearly abolished by mutation of the dileucine motif of IRAP. Immunoblotting of fractions prepared from sucrose gradient ultracentrifugation and vesicles immunopurified with anti-GLUT4 antibody revealed these ACDs to be localized on GLUT4-containing vesicles. Furthermore, 3-mercaptopropionic acid and hexanoyl-CoA, inhibitors of long-chain and medium-chain ACDs, respectively, induced dissociation of long-chain acyl-coenzyme A dehydrogenase and/or medium-chain acyl-coenzyme A dehydrogenase from IRAP in vitro as well as recruitment of GLUT4 to the plasma membrane and stimulation of glucose transport activity in permeabilized 3T3-L1 adipocytes. These findings suggest that ACDs are localized on GLUT4-containing vesicles via association with IRAP in a manner dependent on its dileucine motif and play a role in retention of GLUT4-containing vesicles to an intracellular compartment.
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PMID:Acyl-coenzyme A dehydrogenases are localized on GLUT4-containing vesicles via association with insulin-regulated aminopeptidase in a manner dependent on its dileucine motif. 1198 Oct 39

Insulin resistance-related obesity and diabetes mellitus are the predominant causes of fatty liver disease. Here we examine the effects of dietary diacylglycerol (DG), which is a minor component of plant oils, on lipid accumulation and the expression of genes involved in lipid metabolism in the liver. The animals were fed diets containing either 10% triacylglycerol (TG), 10% TG + 4% alpha-linolenic acid-rich TG (ALATG) or 10% TG + 4% alpha-linolenic acid-rich diacylglycerol (ALADG) for a period of 1 month. Supplementation with ALADG significantly inhibited hepatic triglyceride accumulation; this was accompanied by the up-regulation of beta-oxidation activity, and acyl-CoA oxidase (ACO) and medium-chain acyl-CoA dehydrogenase (MCAD) mRNA levels. By contrast, no significant changes were observed in the levels of peroxisome proliferator-activated receptor-alpha (PPARalpha) and sterol regulatory element-binding protein-1 (SREBP-1) mRNAs. These results indicate that ALADG might be useful in the prevention of fatty liver formation; this effect could be closely related to the stimulation of lipid catabolism in the liver. In addition, our findings suggest that both acylglycerol structure (that is, the structural difference between TG and DG) and fatty-acid species affect the nutritional behaviour of dietary lipids.
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PMID:Supplementation with alpha-linolenic acid-rich diacylglycerol suppresses fatty liver formation accompanied by an up-regulation of beta-oxidation in Zucker fatty rats. 1586 69

Diabetic cardiomyopathy is an important contributor to diastolic and systolic heart failure. We examined the nature and mechanism of the cardiomyopathy in Akita (Ins2(WT/C96Y)) mice, a model of genetic nonobese type 1 diabetes that recapitulates human type 1 diabetes. Cardiac function was evaluated in male Ins2WT/C96Y and their littermate control (Ins2WT/WT) mice using echocardiography and tissue Doppler imaging, in vivo hemodynamic measurements, as well as ex vivo working heart preparation. At 3 and 6 mo of age, Ins2WT/C96Y mice exhibited preserved cardiac systolic function compared with Ins2WT/WT mice, as evaluated by ejection fraction, fractional shortening, left ventricular (LV) end-systolic pressure and maximum rate of increase in LV pressure in vivo, cardiac work, cardiac power, and rate-pressure product ex vivo. Despite the unaltered systolic function, Ins2WT/C96Y mice exhibited significant and progressive diastolic dysfunction at 3 and 6 mo of age compared with Ins2WT/WT mice as assessed by tissue and pulse Doppler imaging (E-wave velocity, isovolumetric relaxation time) and by in vivo hemodynamic measurements (LV end-diastolic pressure, time constant of LV relaxation, and maximum rate of decrease in LV pressure). We found no evidence of myocardial hypertrophy or fibrosis in the Ins2WT/C96Y myocardium. Consistent with the lack of fibrosis, expression of procollagen-alpha type I, procollagen-alpha type III, and fibronectin were not increased in these hearts. Ins2WT/C96Y hearts showed significantly reduced sarcoplasmic reticulum Ca2+-ATPase 2a (cardiac sarcoplasmic reticulum Ca2+ pump) levels, elevated beta-myosin heavy chain isoform, increased long-chain fatty acids, and triacylglycerol with evidence of lipotoxicity, as indicated by a significant rise in ceramide, diacylglycerol, and lipid deposits in the myocardium. Consistent with metabolic perturbation, and a switch to fatty acid oxidation from glucose oxidation in Ins2WT/C96Y hearts, expression of mitochondrial long-chain acyl-CoA dehydrogenase and pyruvate dehydrogenase kinase isoform 4 were increased. Insulin treatment reversed the diastolic dysfunction, the elevated B-type natriuretic peptide and beta-myosin heavy chain, and the reduced sarcoplasmic reticulum Ca2+-ATPase 2a levels with abolition of cardiac lipotoxicity. We conclude that early type 1 diabetic cardiomyopathy is characterized by diastolic dysfunction associated with lipotoxic cardiomyopathy with preserved systolic function in the absence of interstitial fibrosis and hypertrophy.
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PMID:Type 1 diabetic cardiomyopathy in the Akita (Ins2WT/C96Y) mouse model is characterized by lipotoxicity and diastolic dysfunction with preserved systolic function. 1980 94