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)

The authors report on two siblings with a multiple acyl-CoA dehydrogenase deficiency. The first child died from a Reye's syndrome when he was 9 month-old. The diagnosis was made in the neonatal period in his brother. Early treatment with glucose and carnitine should prevent acute attacks.
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PMID:[Multiple acyl-CoA dehydrogenase deficiency. Report of 2 siblings]. 777 88

5,6-Dichloro-4-thia-5-hexenoic acid (DCTH) is toxic to rat liver and kidney mitochondria and is cytotoxic to isolated rat hepatocytes. The object of this investigation was to test the hypothesis that DCTH is bioactivated in vivo by the enzymes of mitochondrial fatty acid beta oxidation and that the observed mitochondrial dysfunction is a consequence of this bioactivation. DCTH was a potent nephrotoxin and hepatotoxin in Long-Evans rats, whereas the odd-chain-length analog 6,7-dichloro-5-thia-6-heptenoic acid was not toxic. DCTH produced morphological changes in renal proximal convoluted tubules and the liver. The increases in urinary protein, glucose and blood urea nitrogen concentrations were consistent with the renal lesions. Hepatic lesions were associated with an increase in plasma glutamate-pyruvate transaminase activity, a marked infiltration of lipid and depletion of glycogen concentrations. A pronounced decrease in plasma glucose concentrations was also observed. DCTH decreased fatty acid beta oxidation by 75% and 40% in liver and kidney mitochondria, respectively, isolated from DCTH-treated rats. In addition, medium-chain acyl-coenzyme A dehydrogenase activity was reduced by 25% in rat liver mitochondria incubated with DCTH. The data presented are consistent with the hypothesis that DCTH is bioactivated by the mitochondrial fatty acid beta-oxidation system and that mitochondria are a critical cellular target in DCTH-induced toxicity.
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PMID:Nephrotoxicity and hepatotoxicity of 5,6-dichloro-4-thia-5-hexenoic acid: evidence for fatty acid beta-oxidation-dependent bioactivation. 796 51

At least 12 fatty acid oxidation disorders are known to be responsible for cases of sudden and unexpected death in early childhood. A specific diagnosis of these disorders is essential for genetic counseling and for the screening of siblings potentially at risk for life-threatening episodes of fasting intolerance. Postmortem blood and urine samples often are not available for further biochemical studies, and currently only medium-chain acyl-CoA dehydrogenase (MCAD) deficiency can be diagnosed by the molecular analysis of tissues. We developed a postmortem screening method for fatty acid oxidation disorders by the simultaneous measurement of C8-C20 fatty acids, glucose, lactate, and other metabolites from the methanol wash of a pellet obtained by ultracentrifugation of liver homogenate. Cis-4-decenoic acid was present in five confirmed cases with MCAD deficiency and in one case with glutaric aciduria type II and was absent in 97 of 100 randomly chosen sudden death cases, at least 81 of which were diagnosed as sudden infant death syndrome (SIDS). C14-C18 monounsaturated fatty acids were significantly elevated in the one examined case affected with long-chain acyl-CoA dehydrogenase (LCAD) deficiency. The metabolite profiles in two cases with carnitine uptake deficiency were less informative, but they shared with all the other disease controls a very low glucose concentration, a finding compatible with premortem hypoglycemia. This method is proposed as a simple and practical means of biochemical screening to follow up the postmortem finding of liver fat infiltration.
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PMID:Biochemical diagnosis of fatty acid oxidation disorders by metabolite analysis of postmortem liver. 805 17

Fatty acid beta-oxidation was studied in organellar fractions from maize root tips by h.p.l.c. and radiometric analysis of the products of incubations with [1-14C]octanoate and [1-14C]palmitate. In crude organellar fractions containing both mitochondria and peroxisomes, octanoate and palmitate beta-oxidation, as determined by the production of acetyl-CoA, was functional and, for palmitate, was activated 4-12-fold after subjecting the root tips to 48 h of glucose starvation. The sensitivity to a 'cocktail' of respiratory-chain inhibitors containing cyanide, azide and salicylhydroxamate depended on the conditions of incubation, with no inhibition in a medium facilitating peroxisomal beta-oxidation and a significant inhibition in a medium potentially facilitating mitochondrial beta-oxidation. Indeed, preparations of highly purified mitochondria from glucose-starved root tips were able to oxidize octanoate and palmitate to give organic acids of the tricarboxylic acid cycle. This activity was inhibited 5-10-fold by the above cocktail of respiratory-chain inhibitors, with no parallel accumulation of acetyl-CoA, thus showing that the inhibition affected beta-oxidation rather than the pathway from acetyl-CoA to the organic acids. This provides the first evidence that the complete beta-oxidation pathway from fatty acids to citrate was functional in mitochondria from a higher plant. Moreover, an acyl-CoA dehydrogenase activity was shown to be present in the purified mitochondria. In contrast with the peroxisomal activity, mitochondrial beta-oxidation showed the same efficiency with octanoate and palmitate and was strictly dependent on glucose starvation.
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PMID:Effects of glucose starvation on the oxidation of fatty acids by maize root tip mitochondria and peroxisomes: evidence for mitochondrial fatty acid beta-oxidation and acyl-CoA dehydrogenase activity in a higher plant. 825 Aug 43

Patients with an acyl-CoA dehydrogenase deficiency share the disease features of hypoglycemia, hyperammonemia, tissue fatty change, hypoketonemia, carnitine deficiency, and organic acidemia due to apparent disruption of normal fatty acid, glucose, and urea metabolism. Most of the acute clinical episodes occur in young children. These episodes are precipitated by fasting and are often fatal, with the in vivo mechanisms essentially unknown. Since the genes of the rate controlling enzymes of these pathways are tissue and developmentally regulated at the transcriptional level, we measured, throughout neonatal development, the steady-state mRNA levels of long-chain, medium-chain, and short-chain (SCAD) acyl-CoA dehydrogenases, pyruvate carboxylase (PC), phosphoenolpyruvate carboxykinase (PEPCK), carbamyl phosphate synthetase I (CPS), ornithine transcarbamylase (OTC), and argininosuccinate synthetase (AS) in fed or fasted SCAD-deficient BALB/ByJ mice compared to BALB/cBy controls. Overall, our results showed no major effects on expression of acyl-CoA dehydrogenases due to SCAD deficiency, regardless of age or fasting. In SCAD-deficient mice we found depressed mRNA expression and enzyme activity for the urea cycle enzymes CPS and AS at 6 days of age, and found no apparent effects on expression of gluconeogenic enzymes PC or PEPCK. There was a period of overall lower gene expression for most genes at 6 and 15 days, which appears to be in parallel with the developmental period when children with these diseases are most severely affected.
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PMID:Effects of short-chain acyl-CoA dehydrogenase deficiency on development expression of metabolic enzyme genes in the mouse. 873 88

To identify genes expressed at intermediate stages of Bacillus subtilis sporulation, we screened for sigma E-dependent promoters. One promoter that we found drives expression of an operon consisting of at least five open reading frames (ORFs). The predicted products of the first three ORFs are very homologous to enzymes involved in fatty acid metabolism, including acetyl coenzyme A (acetyl-CoA) acetyltransferase (thiolase), 3-hydroxybutyryl-CoA dehydrogenase, and acyl-CoA dehydrogenase, respectively. We showed that the fourth ORF encoded a third isozyme of citrate synthase in B. subtilis. Genetic evidence and primer extension results showed that transcription of this operon is directed by the mother cell compartment-specific sigma factor, sigma E, and so the operon was named mmg (for mother cell metabolic genes). Furthermore, we found that a sequence (mmgO) with homology to a catabolite-responsive element mediates glucose repression of mmg promoter activity during sporulation and that this repression was lost in a ccpA mutant.
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PMID:A sigma E dependent operon subject to catabolite repression during sporulation in Bacillus subtilis. 875 38

The activity of hepatic fatty acid oxidation enzymes in rats fed linseed and perilla oils rich in alpha-linolenic acid (alpha-18:3) was compared to that in rats fed safflower oil rich in linoleic acid (18:2) and a saturated fat (palm oil). Palm and safflower oils were essentially devoid of alpha-18:3. The palmitoyl-CoA oxidation rates both in mitochondrial and peroxisomal pathways in liver homogenates were significantly higher in rats fed linseed oil than in those fed palm and safflower oils. Among rats fed diets containing palm oil, safflower oil, fat mixtures composed of safflower and perilla oils (2:1, w/w and 1:2, w/w), and perilla oil, mitochondrial and peroxisomal fatty oxidation rates increased with increasing dietary levels of perilla oil. Compared to palm and safflower oils, dietary alpha-18:3 either in the form of linseed or perilla oils profoundly increased the activity of carnitine palmitoyltransferase, acyl-CoA oxidase, 3-ketoacyl-CoA thiolase, and 2,4-dienoyl-CoA reductase. Smaller but significant increases by dietary alpha-18:3 of the activity of acyl-CoA dehydrogenase, enoyl-CoA hydratase, and delta 3, delta 2-enoyl-CoA isomerase were also observed. Unexpectedly, dietary alpha-18:3 greatly reduced the activity of 3-hydroxy-acyl-CoA dehydrogenase. Compared to palm oil, dietary polyunsaturated fats significantly reduced the activity of fatty acid synthetase and glucose-6-phosphate dehydrogenase to the same levels. The activity of pyruvate kinase was significantly higher in rats fed palm oil than in those fed polyunsaturated fats. The extent of reduction was more prominent with polyunsaturated fats containing alpha-18:3 than with safflower oil devoid of alpha-18:3. Thus, compared to linoleic acid and saturated fatty acids, dietary alpha-18:3 caused characteristic changes in the activity of hepatic enzymes in fatty acid and glucose metabolism in rats.
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PMID:Activity of hepatic fatty acid oxidation enzymes in rats fed alpha-linolenic acid. 895 34

Since 1911, blood sugars have been measured in newborn infants. Significant neonatal hypoglycemia was first reported in 1937. In 1959, the report of transient symptomatic neonatal hypoglycemia generated worldwide reports. This, along with the ongoing advances in studies of energy metabolism, thermal control and oxygen requirements, led to the first conference on Energy and Carbohydrate Metabolism in the newborn in Tokyo, 1965. Subsequently, a number of hypoglycemia syndromes were discovered. Concurrently, pre-, peri- and neonatal care changed dramatically with the survival or very tiny and very sick newborns. These advances in care made previously derived statistical definitions of hypoglycemia irrelevant. New functional definitions are needed to define abnormal glucose concentrations. Significant hypoglycemia is a continuum of low glucose concentrations of varied duration and severity. Its impact depends upon other risk factors as well. In addition, new hypoglycemic syndromes have appeared. These include deficiencies of blood-brain glucose transporters, the association of hyperinsulinemic hypoglycemia with isoimmune thrombocytopenia and a variety of acyl CoA dehydrogenase deficiencies. Concurrently, carbohydrate disorders in infancy appear to be changing. Neonatal diabetes mellitus, previously transient and benign, now shows a high frequency of recurrence and remaining as a permanent condition. Idiopathic ketotic hypoglycemia of infancy has disappeared in the USA. Familial hyperinsulinemic hypoglycemic syndromes of infancy appear to have a good prognosis, respond to medical intervention and have had their genetic defect localized to a specific gene. Current advances promise reliable bedside techniques to measure central nervous system function, cerebral blood flow, endocrine hormones and receptors as well as glucose transporters and specific genetic defects. These data, when correlated with plasma glucose concentrations and central nervous system function and development, should provide a better understanding of the impact of prolonged and profound hypoglycemia on long-term outcome.
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PMID:Neonatal hypoglycemia 30 years later: does it injure the brain? Historical summary and present challenges. 920 Aug 72

During cardiac hypertrophy and in the failing heart, the chief myocardial energy substrate switches from fatty acids to glucose. In this review, we describe recent progress in the elucidation of the molecular regulatory events involved in the dramatic downregulation of the expression of fatty acid utilization enzymes during development of cardiac hypertrophy and failure. Much of this work has focused on the gene encoding medium-chain acyl-CoA dehydrogenase (MCAD), which catalyzes a pivotal step in the mitochondrial fatty acid -oxidation (FAO) cycle. In vivo ventricular pressure overload studies performed in mice transgenic for human MCAD promoter fragments linked to reporter genes have shown that transcription is markedly downregulated within seven days of pressure overload. The temporal pattern of this alteration in MCAD gene expression has also been characterized in a rat model of progressive pressure overload-induced left ventricular hypertrophy (LVH) and heart failure (HF) [SHHF/Mcc-facp (SHHF) rat]. MCAD mRNA levels are downregulated (>70%) during both the LVH and HF stages in the SHHF rats compared with controls. In contrast, the activity and immunodetectable levels of MCAD enzyme were not significantly reduced until the HF stage, indicating additional compensatory control at the translational or post-translational levels in the hypertrophied but non-failing ventricle. FAO enzyme expression was also shown to be downregulated in human subjects with dilated cardiomyopathy compared to age-matched controls. Taken together, these results have identified a gene regulatory program that is involved in the alterations in myocardial energy substrate utilization in the failing heart. The temporal correlation of diminished enzyme expression with onset of heart failure suggests that this alteration in lipid metabolism may play a role in the pathogenesis of pressure-overload induced heart failure. This gene regulatory pathway should be a useful target for experimental studies aimed at the molecular pathogenesis of the transition from stable cardiac hypertrophy to overt heart failure.
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PMID:The energy substrate switch during development of heart failure: gene regulatory mechanisms (Review). 985 94

The activities of beta-oxidation enzymes were measured in extracts of glucose- and triolein-grown cells of Aspergillus niger. Growth on triolein stimulated increased enzyme activity, especially for acyl-CoA dehydrogenase. No acyl-CoA oxidase activity was detected. HPLC analysis after incubation of triolein-grown cell extracts with decanoyl-CoA showed that beta-oxidation was limited to one cycle. Octanoyl-CoA accumulated as the decanoyl-CoA was oxidized. Beta-oxidation enzymes in isolated mitochondrial fractions were also studied. The results are discussed in the context of methyl ketone production by fungi.
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PMID:Oxidation of medium-chain acyl-CoA esters by extracts of Aspergillus niger: enzymology and characterization of intermediates by HPLC. 1020 7


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