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)

A 985A-->G transition is the single prevalent mutation representing 89% of all variant medium-chain acyl-CoA dehydrogenase (MCAD) alleles that causes MCAD deficiency. We and others previously devised a molecular method for the detection of the 985G allele that involves PCR coupled with NcoI digestion. The method has been widely used. However, when used for the analysis of dried blood samples, it sometimes produced ambiguous results with weak target bands in the presence of numerous artifact bands. An improved version of the method has been developed here, involving two stages of amplification using two different sets of primers. In the first stage, the entire exon-11 was amplified. A small aliquot (5 microliters) of the first PCR products were directly used as a template for the second PCR amplification. The second PCR is similar to the original method, but utilizes a pair of primers encompassing a smaller section within exon-11. The upstream primer incorporates a substitution at 981, so that a NcoI site involving 985G is introduced in the copies of the variant allele, as in the original PCR/NcoI method. The improved 2-stage method produces an intense target band with a very high sensitivity, yet devoid of artifacts, providing clean, unequivocal results.
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PMID:Improved PCR/NcoI method for the molecular diagnosis of medium chain acyl-CoA dehydrogenase deficiency using dried blood samples: two-stage amplification using two different sets of primers improves accuracy and sensitivity. 811 61

The purpose of this study was to determine whether treatment with L-carnitine or acetyl-L-carnitine enhances the turnover of lipid or branched-chain amino acid oxidation in patients with inborn errors of metabolism. Increasing i.v. doses of L-carnitine and acetyl-L-carnitine were given to one patient with medium-chain acyl-CoA dehydrogenase deficiency and to another with isovaleric acidemia. Both patients were in stable condition and receiving oral L-carnitine supplements. The excretion of carnitine and disease-specific metabolites was measured. The incorporation of L-carnitine in the intracellular pool was demonstrated using stable isotopes and mass spectrometry. Increasing doses of either i.v. L-carnitine or acetyl-L-carnitine did not stimulate the excretion of octanoylcarnitine in the patient with medium-chain acyl-CoA dehydrogenase deficiency, nor did it raise the plasma levels of either cis-4-decenoate or octanoylcarnitine. Similarly, increasing doses of either i.v. L-carnitine or acetyl-L-carnitine did not enhance the excretion of isovalerylcarnitine in a patient with isovaleric acidemia. The excretion of isovalerylglycine actually decreased. We conclude that there was no evidence of enhanced fatty acid beta-oxidation or enhanced branched-chain amino acid oxidation in vivo by the administration of high doses of L-carnitine or acetyl-L-carnitine in these two patients. Because only one individual with each disorder was studied, the data are only indicative and may not necessarily be representative of all individuals with these disorders. Definite settlement of this issue will require further studies in additional subjects.
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PMID:Intravenous L-carnitine and acetyl-L-carnitine in medium-chain acyl-coenzyme A dehydrogenase deficiency and isovaleric acidemia. 813 5

We have developed methods for the measurement of the medium-chain fatty acids octanoate, decanoate and cis-4-decenoate and the acylglycines n-hexanoylglycine (HG) and 3-phenylpropionylglycine (PPG) in blood spots using gas chromatography and mass spectrometry. Normal ranges were obtained for octanoate and decanoate. HG, PPG and cis-4-decenoic acid were not detected in control blood spots. In blood spots from nine patients (including two newborn) with medium-chain acyl-CoA dehydrogenase (MCAD) deficiency, all metabolites were present in elevated concentrations although PPG was close to the detection limits and there was overlap for octanoate and decanoate. The lack of detection of cis-4-decenoic acid and HG in controls suggests that these are the metabolites of choice for blood spot identification of infants with MCAD deficiency.
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PMID:Population screening for medium-chain acyl-CoA dehydrogenase deficiency: analysis of medium-chain fatty acids and acylglycines in blood spots. 815 55

A female patient with medium-chain acyl-CoA dehydrogenase (MCAD) deficiency developed normally until 13 months of age after which she showed a gradual developmental delay, followed by progressive dementia, and a decrease in head circumference growth culminating in the diagnosis of Rett syndrome at 3.5 years.
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PMID:Rett syndrome in a patient with medium chain acyl-CoA dehydrogenase deficiency. 819 60

This paper describes a method for the quantitative determination of free carnitine, acetylcarnitine, propionylcarnitine, hexanoylcarnitine, octanoylcarnitine, and total carnitine in plasma. Carnitine and acylcarnitines were extracted from 100 microliters of plasma with acetonitrile/methanol and isolated using 0.5-ml columns of silica gel. Samples were then derivatized with 4'-bromophenacyl trifluoromethanesulfonate and quantified by high-performance liquid chromatography with detection at 260 nm. Carnitine and acylcarnitines were quantified in normal human plasma and the plasma of patients diagnosed with methylmalonic aciduria, propionic acidemia, and medium-chain acyl-CoA dehydrogenase deficiency.
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PMID:Quantification of free carnitine, individual short- and medium-chain acylcarnitines, and total carnitine in plasma by high-performance liquid chromatography. 821 94

Mammalian electron-transferring flavoprotein (ETF) has been reported to consist of two non-identical subunits and one FAD. The present paper shows that ETF purified from pig kidney contains one more molecule, an AMP. ETF was denatured by guanidine hydrochloride and ultrafiltered for the purpose of removing proteins. The filtrate was analyzed by reverse-phase chromatography. Two peaks appeared on the chromatogram: they were identified as FAD and AMP, and their molar amounts were identical, indicating that ETF contains one AMP molecule. ApoETF, which was prepared by KBr treatment of ETF, also contains one AMP molecule. ApoETF, which was prepared by KBr treatment of ETF, also contain one AMP molecule. These results clearly demonstrate that ETF has an AMP-binding site in addition to the FAD-binding site. AMP-free apoETF was prepared by guanidine treatment of ETF. Mixing AMP-free apoETF, FAD, and AMP produced reconstituted ETF, which showed the same properties as native ETF. Mixing AMP-free apoETF and FAD produced AMP-free ETF, regardless of the coexistence of ATP or ADP: the AMP-binding site cannot bind FAD, ADP, or ATP. The enzymatic activity of the AMP-free ETF for electron transfer from substrate-reduced medium-chain acyl-CoA dehydrogenase to 2,6-dichlorophenolindophenol was identical to that of native ETF. This indicates that the AMP contained in holoETF has no apparent influence on this enzymatic activity. A role of AMP recognized in this study is that AMP facilitates the formation of holoETF from AMP-free apoETF, FAD, and AMP.
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PMID:Electron-transferring flavoprotein has an AMP-binding site in addition to the FAD-binding site. 826 2

Utilization of fatty acids for energy varies among mammalian tissues and during development due to changes in expression of enzymes of mitochondrial beta oxidation. To discern whether two related nuclear genes are expressed similarly, the tissue distribution and developmental profile of the rat long- and medium-chain acyl-CoA dehydrogenase (LCAD and MCAD) mRNAs were compared. A 1451 base full-length LCAD cDNA from neonatal rat aorta was used to study mRNA accumulation in adult and fetal rat tissues. LCAD and MCAD mRNAs were expressed in aorta, heart, and brown fat at levels 8-40 fold greater than in liver, kidney, and duodenum. Brain, placenta, ovary, testes, and skeletal muscle showed the least mRNA. Western blots of adult tissues with anti-rat LCAD antiserum showed corresponding amounts of LCAD protein subunits. LCAD mRNA was detectable in heart, liver, kidney, and brain of fetal rats and increased with age. LCAD and MCAD mRNAs were present in brown fat in 2-10 fold greater amounts compared to other tissues from the newborn period to the end of the weaning period. The high level of expression of LCAD and MCAD mRNA in aorta, heart, and brown fat likely reflects the high energy requirements of those tissues. Differential expression of LCAD and MCAD mRNAs reflects not only inherent gene prescribed programs, but also external influences such as hormones and diet.
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PMID:Tissue specific and developmental expression of rat long-and medium-chain acyl-CoA dehydrogenases. 826 28

Short-chain acyl-CoA dehydrogenase (SCAD) is one of five homologous dehydrogenases that catalyze the first reaction in the beta-oxidation of fatty acids. As the name implies, the substrate for this enzyme is short-chain acyl-CoA (C4-C6). We report here the coding and 3'UT sequence of the cDNA for mouse precursor SCAD. The mouse SCAD cDNA coding sequence covers 1239 bp. This represents a 24-amino-acid leader peptide and a 388-amino-acid mature peptide. Comparison of this sequence with reported rat and human SCAD cDNA sequences reveals a high degree of homology among the three species. Comparison of the amino acid sequence with that of other acyl-CoA dehydrogenases, medium-chain acyl-CoA dehydrogenase and long-chain acyl-CoA dehydrogenase, also shows a high degree of homology.
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PMID:Cloning and characterization of the mouse short-chain acyl-CoA dehydrogenase cDNA. 827 99

An infant with glycogen storage disease and prolonged malnourishment showed a urinary organic acid profile during an episode of fasting hypoglycaemia with inappropriate hypoketotic dicarboxylic aciduria that was indistinguishable from that reported in long-chain L-3-hydroxyacyl-CoA dehydrogenase deficiency. Although there was a striking elevation of urinary 3-hydroxydecanedioic acid, the ratios between hydroxydicarboxylic acids were consistent with values reported to be indicate of medium-chain acyl-CoA dehydrogenase deficiency. We suspect that the fasting 3-hydroxydicarboxylic aciduria was attributable to secondarily impaired enzyme activities, the consequence of malnutrition, early infancy, and/or glycogen storage disease. Caution is advised in the interpretation of urinary organic acid patterns that indicate a 3-hydroxydicarboxylic aciduria, as well as an inappropriate hypoketotic dicarboxylic aciduria, as they may represent non-specific findings.
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PMID:Marked elevation of urinary 3-hydroxydecanedioic acid in a malnourished infant with glycogen storage disease, mimicking long-chain L-3-hydroxyacyl-CoA dehydrogenase deficiency. 829

A number of rare inherited metabolic disorders are known to lead to death in infancy. Deficiency of medium-chain acyl CoA dehydrogenase has, on clinical grounds, been related particularly to sudden infant death syndrome. The contribution of this disorder to the etiology of sudden infant death syndrome is still a matter of controversy. The present study investigated 120 well-defined cases of sudden infant death syndrome in order to detect the frequency of the most common disease-causing point mutation in the gene coding for medium-chain acyl-CoA dehydrogenase (G985) compared with the frequency in the general population. A highly specific polymerase chain reaction assay was applied on dried blood spots. No over-representation of homo- or heterozygosity for G985 appears to exist in such a strictly defined population, for which reason it may be more relevant to look at a broader spectrum of clinical presentations of inherited metabolic disorders and examine a wider range of sudden death in infancy.
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PMID:The frequency of a disease-causing point mutation in the gene coding for medium-chain acyl-CoA dehydrogenase in sudden infant death syndrome. 833 87


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