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:1.3.99.3 (acyl-CoA dehydrogenase)
1,425 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In summary, the vitamin pantothenic acid is an integral part of the acylation carriers, CoA and acyl carrier protein (ACP). The vitamin is readily available from diverse dietary sources, a fact which is underscored by the difficulty encountered in attempting to induce pantothenate deficiency. Although pantothenic acid deficiency has not been linked with any particular disease, deficiency of the vitamin results in generalized malaise clinically. In view of the fact that pantothenate is required for the synthesis of CoA, it is surprising that tissue CoA levels are not altered in pantothenate deficiency. This suggests that the cell is equipped to conserve its pantothenate content, possibly by a recycling mechanism for utilizing pantothenate obtained from degradation of pantothenate-containing molecules. Although the steps involved in the conversion of pantothenate to CoA have been characterized, much remains to be done to understand the regulation of CoA synthesis. In particular, in view of what is known about the in vitro regulation of pantothenate kinase, it is surprising that the enzyme is active in vivo, since factors that are known to inhibit the enzyme are present in excess of the concentrations known to inhibit the enzyme. Thus, other physiological regulatory factors (which are largely unknown) must counteract the effects of these inhibitors, since the pantothenate-to-CoA conversion is operative in vivo. Another step in the biosynthetic pathway that may be rate limiting is the conversion of 4'-phosphopantetheine (4'-PP) to dephospho-CoA, a step catalyzed by 4'-phosphopantetheine adenylyl-transferase. In mammalian systems, this step may occur in the mitochondria or in the cytosol. The teleological significance of these two pathways remains to be established, particularly since mitochondria are capable of transporting CoA from the cytosol. Altered homeostasis of CoA has been observed in diverse disease states including starvation, diabetes, alcoholism, Reye syndrome (RS), medium-chain acyl CoA dehydrogenase deficiency, vitamin B12 deficiency, and certain tumors. Hormones, such as glucocorticoids, insulin, and glucagon, as well as drugs, such as clofibrate, also affect tissue CoA levels. It is not known whether the abnormal metabolism observed in these conditions is the result of altered CoA metabolism or whether CoA levels change in response to hormonal or nonhormonal perturbations brought about in these conditions. In other words, a cause-effect relation remains to be elucidated. It is also not known whether the altered CoA metabolism (be it cause or result of abnormal metabolism) can be implicated in the manifestations of a disease. Besides CoA, pantothenic acid is also an integral part of the ACP molecule.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Pantothenic acid in health and disease. 174 61

At the time of acute presentation, children with carnitine deficiency may have increased free fatty acid concentrations and hypoglycemia. However, whether carnitine replacement affects the plasma concentration of these substrates remains to be determined. Therefore, to evaluate the effect of carnitine replacement on plasma substrate and hormone concentrations, five children with carnitine deficiency (two idiopathic, two secondary to long-chain acyl coenzyme A dehydrogenase deficiency, one secondary to isovaleric acidemia) were fasted overnight before and after treatment with oral carnitine (80 +/- 7 mg.kg-1.day-1). During carnitine supplementation, plasma total carnitine (19 +/- 4 versus 45 +/- 6 nmol/ml, pretreatment versus treatment, respectively) and free carnitine (11 +/- 3 versus 31 +/- 6 nmol/ml), as well as red blood cell total carnitine (0.057 +/- 0.019 versus 0.130 +/- 0.019 nmol/mg of hemoglobin) increased (p less than 0.05). Fasting plasma glucose (83 +/- 4 versus 85 +/- 3 mg/dl) and ketone body (0.54 +/- 0.18 and 0.56 +/- 0.20 mM) concentrations did not change with carnitine supplementation, but plasma free fatty acids (1.28 +/- 0.32 versus 0.77 +/- 0.07 mM) decreased (p less than 0.05). No differences in fasting insulin, growth hormone, or cortisol concentrations were observed. Urinary excretion of free carnitine (0.1 +/- 0.0 versus 2.4 +/- 0.7 mumol/mg creatinine), total carnitine (0.3 +/- 0.1 versus 3.4 +/- 0.9 mumol/mg creatinine) and acyl carnitine (0.2 +/- 0.1 versus 0.9 +/- 0.3 mumol/mg creatinine) increased (p less than 0.05) with carnitine supplementation. The decreased plasma free fatty acid concentrations with carnitine supplementation may be due to more efficient fatty acid oxidation and/or increased urinary excretion of fatty acids as acylcarnitines.
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PMID:Decreased fasting free fatty acids with L-carnitine in children with carnitine deficiency. 329 Aug 28

Seven middle-aged men with manifest type II diabetes mellitus underwent an endurance training programme for 10-15 weeks. The maximal aerobic capacity, as well as the endurance capacity, was improved by 10% (p less than 0.05). The intramuscular glycogen store increased by more than 80% (p less than 0.05) from 350 mumol/g dw (dry weight), and the activities of citrate synthase and 3-hydroxy-acyl-CoA dehydrogenase increased by more than 50% (p less than 0.05) and 30% (p less than 0.05). The activity of glycogen synthase was decreased by approximately 20% (p less than 0.05), whereas lactate dehydrogenase remained unchanged. Capillaries/fibre and fibre area increased by more than 50% (p less than 0.05) and 30% (p less than 0.05) leaving the area of supply constant. Training did not influence fasting blood lipids and glucose, glycosylated hemoglobin, oral glucose tolerance, and insulin response to an oral glucose load measured 72 hours post-exercise. It is concluded that patients with manifest type II diabetes, as normoglycaemic individuals, adapt to physical training. However, no persistent effect on glucohomeostasis and lipaemia is produced by short-term training in the diabetic patients.
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PMID:Skeletal muscle adaptations to physical training in type II (non-insulin-dependent) diabetes mellitus. 336 17

Men with regular physical training habits voluntarily increased their dietary fat intake from 43 to 54% of energy (E%) for four weeks. This was followed by a low-fat (29 E%), high-carbohydrate diet for another four weeks. During the high-fat diet period, the muscle lipoprotein lipase activity (LPLA) increased from 59 +/- 8 to 106 +/- 12 mU/g (mean +/- SE) (P less than 0.05). After the high-carbohydrate diet, LPLA was 57 +/- 16 mU/g, and unchanged relative to the pre-trial value. The triglyceride content in m. vastus lateralis increased from 30 +/- 4 to 47 +/- 9 mmol/kg d.w. (P less than 0.05; mean +/- SE) following the high-fat diet and to 41 +/- 8 following the high-carbohydrate diet. Neither of the diets affected the serum triglyceride and insulin concentrations, nor glucose, glycerol, beta-hydroxybutyrate, citrate and lactate levels in the blood. Nor did they alter enzyme activities in muscle used as markers for the oxidative (citrate synthase, beta-hydroxy-acyl CoA dehydrogenase) and glycolytic (glyceraldehyde phosphate dehydrogenase, lactate dehydrogenase) capacity. It is concluded that one month's adaptation to a high-fat diet results in increased muscle-LPL activity indicating a higher capacity for uptake of fatty acids from circulating serum triglycerides into the muscle cell in association with a greater capacity for triglyceride storage in the muscle. Under these conditions serum triglycerides were not decreased despite the increased muscle LPLA, and serum insulin variations could not explain the change in muscle LPLA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lipoprotein lipase activity and intramuscular triglyceride stores after long-term high-fat and high-carbohydrate diets in physically trained men. 354 51

The effect of altering the percent of dietary carbohydrate on the rate of skeletal muscle glucose uptake was studied using the perfused rat hindlimb preparation. The rats received either a high carbohydrate (HC; 65%), mixed (M; 35%) or low carbohydrate (LC; 10%) isocaloric diet for 7 days. With 0.1 mU/ml of insulin in the perfusate, the muscle of rats on the HC diet had a 33% increase in the rate of glucose uptake and the muscle of rats fed the LC diet a 23% decrease in the rate of glucose uptake when compared to the muscle of rats fed the M diet (3.34 mumol/g/30 min). With 10.0 mU/ml of insulin in the perfusate, ie maximal insulin stimulation, the rate of glucose uptake showed a similar dietary effect as that obtained with 0.1 mU/ml insulin. Compared to the M diet (8.67 mumol/g/30 min), the rate of glucose uptake increased 26% in muscle of rats from the HC group and decreased by 20% in muscle of rats from the LC group. Diet had no effect on the rate of muscle glucose uptake in the absence of insulin. Under both maximal and submaximal insulin stimulation, glycogen accumulation was greatest in muscle from HC fed rats and least in muscle from LC fed rats. During perfusion muscle intracellular free glucose and glucose-6-phosphate accumulation for the three dietary groups was negligible. The groups did not differ significantly in their muscle hexokinase or beta-hydroxyl acyl CoA dehydrogenase activities.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Influence of dietary carbohydrate on skeletal muscle glucose uptake. 397 51

Morris 7800 C1 hepatoma cells were grown in the presence of 80 microM tetradecylthioacetic acid (TTA), a peroxisome proliferator, for 1 year (long-term-treated cells). The growth of the Morris 7800 C1 hepatoma cells was inhibited in cells treated with TTA for up to 8 days. Treatment of the cells with TTA for 1 year did not reduce growth further. The growth inhibition was easily reversed by insulin (0.4 microM). Peroxisomal acyl-CoA oxidase (ACO) (EC 1.3.99.3) activity was increased 5.5 times in cells treated with TTA for 3 days. In the cells treated with TTA for 1 year the ACO activity was increased only two times. A similar ACO mRNA half-life (two times the control) was found in cells treated with TTA for 1 year and for 3 days. This implies a loss of effect of TTA on the transcription rate of the ACO gene in long-term-treated cells.
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PMID:The effects of long-term administration of 3-thia fatty acid, a peroxisome proliferator, to Morris 7800 C1 hepatoma cells. 821 84

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

Accumulation of acyl-CoA is hypothesized to be involved in development of insulin resistance. Acyl-CoA binds to acyl-CoA binding protein (ACBP) with high affinity, and therefore knowledge about ACBP concentration is important for interpreting acyl-CoA data. In the present study, we used a sandwich enzyme-linked immunosorbent assay to quantify ACBP concentration in different muscle fiber types. Furthermore, ACBP concentration was compared in muscles from lean and obese Zucker rats. Expression of ACBP was highest in the slow-twitch oxidative soleus muscle and lowest in the fast-twitch glycolytic white gastrocnemius (0.46 +/- 0.02 and 0.16 +/- 0.005 microg/mg protein, respectively). Expression of ACBP was soleus > red gastrocnemius > extensor digitorum longus > white gastrocnemius. Similar fiber type differences were found for carnitine palmitoyl transferase (CPT)-1, and a correlation was observed between ACBP and CPT-1. Muscles from obese Zucker rats had twice the triglyceride content, had approximately twice the long-chain acyl CoA content, and were severely insulin resistant. ACBP concentration was approximately 30% higher in all muscles from obese rats. Activities of CPT-1 and 3-hydroxy-acyl-CoA dehydrogenase were increased in muscles from obese rats, whereas citrate synthase activity was similar. In conclusion, ACBP expression is fiber type-specific with the highest concentration in oxidative muscles and the lowest in glycolytic muscles. The 90% increase in the concentration of acyl-CoA in obese Zucker muscle compared with only a 30% increase in the concentration of ACBP supports the hypothesis that an increased concentration of free acyl-CoA is involved in the development of insulin resistance.
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PMID:Acyl-CoA binding protein expression is fiber type- specific and elevated in muscles from the obese insulin-resistant Zucker rat. 1181 54

In a previous report, we observed an altered proportion of fiber types and a reduction of capillary per fiber ratio in extensor digitorus longus (EDL) and soleus (SOL) muscles of deoxicorticosterone acetate (DOCA)-salt hypertensive rats when compared with controls. The aim of the present study was to ascertain various carbohydrate and lipid enzyme activities and substrates that may be involved in the morphological changes reported. In the SOL muscle of hypertensive rats, glucose, glycogen and triglycerides (TG) levels were increased, citrate synthase (CS) and beta-hydroxy-acyl-CoA dehydrogenase (HAD) activities were reduced, while hexokinase (HK) and lipoprotein lipase (LPL), LPL mass, lactate and free fatty acids (FFA) levels were unchanged. In EDL muscles of hypertensive rats, glycogen levels and LPL mass were higher than in controls, while CS, HAD, HK, and LPL activities and glucose, lactate, FFA and TG levels were unmodified. Serum levels of insulin, TG, cholesterol and FFA were increased while glucose levels were decreased and high-density lipoprotein-cholesterol levels were similar in hypertensive rats when compared with controls. In conclusion, hypertensive rats showed increased glycogen in both EDL and SOL muscles, with hyperinsulinemia and reduced glycemia. Hyperinsulinemia might have been a compensatory response to insulin resistance. The oxidative capacity of SOL muscle was reduced indicating that glucose uptake was conduced via non-oxidative metabolism. TG, FFA and cholesterol were increased in serum and TG in SOL muscle.
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PMID:Metabolic changes in DOCA-salt hypertensive rats. 1191 12

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


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