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)

Resonance Raman (RR) spectra of the complex of pig kidney medium-chain acyl-CoA dehydrogenase with acetoacetyl-CoA and of the purple complex formed upon the addition of octanoyl-CoA to the dehydrogenase were obtained. RR spectra were also measured for the complexes prepared by using isotopically labeled compounds, i.e., [3-13C]-, [1,3-13C]-, and [2,4-13C2]acetoacetyl-CoA; [1-13C]octanoyl-CoA; the dehydrogenase reconstituted with [4a-13C]- and [4,10a-13C2]FAD. Both bands of oxidized flavin and acetoacetyl-CoA were resonance-enhanced in the 632.8 nm excited spectra of the acetoacetyl-CoA complex; this confirms that the broad long-wavelength absorption band is a charge-transfer absorption band between oxidized flavin and acetoacetyl-CoA. The 1,622 cm-1 band was assigned to the C(3)=O stretching mode coupling with the C(2)-H bending mode of the enolate form of acetoacetyl-CoA and the bands at 1,483 and 1,119 cm-1 were assigned to bands associated with the C(2)=C(1)-O- moiety. Both bands of fully reduced flavin and the substrate were resonance-enhanced in the 632.8 nm excited spectra of the purple complex. As the enzyme is already reduced, the substrate must be oxidized to octenoyl-CoA; the complex is a charge-transfer complex between the reduced enzyme and octenoyl-CoA. The low frequency value of the 1,577 cm-1 band, which is associated with the C(2)-C(1)=O moiety of the octenoyl-CoA, suggests that the enzyme-bound octenoyl-CoA has an appreciable contribution of C(2)=C(1)-O-.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Resonance Raman study on complexes of medium-chain acyl-CoA dehydrogenase. 150 Apr 13

Treatment of 17 children aged 2-9.5 years with a combination of pivmecillinam and pivampicillin (250-500 mumol 24 h-1) for more than 1 year resulted in a reduction of the free carnitine concentration in serum and muscle to less than 10% of the mean reference value. The decline in serum was slow, with an estimated half-life of about 5 months. Spontaneous replenishment occurred at about the same slow rate. Thus, there is no increase in endogenous carnitine synthesis as a response to increased demand of carnitine for detoxification. Supplementation with carnitine during treatment required at least a four-fold molar excess over pivalic acid to achieve and sustain a normal carnitine concentration. The replenishment of carnitine occurred with a half-life of 1.1-3.0 months. From determination of muscle-carnitine concentration in patients treated with pivaloyl-containing antibiotics and in patients with organic aciduris, we conclude that serum carnitine is a good predictor of carnitine stores in the body. Six non-supplemented patients with a serum free-carnitine concentration of 0.7-2.6 mumol l-1 had an inadequate ketone-body increase during a 24-h fast. Vomiting, nausea and tiredness occurred in three cases following the fasting period. After normalization of the serum-carnitine concentration, a normal response to fasting was observed. Thus, in some organic acidurias, for example medium-chain acyl-CoA dehydrogenase deficiency, a low liver concentration of carnitine may be an important contributing factor to hypoglycaemic and Reye-like attacks. We believe that prodrugs which contain pivalic acid should be avoided if acceptable alternatives exist. If used, supplementation with at least four-fold molar excess of carnitine is advisable.
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PMID:Effects of pivalic acid-containing prodrugs on carnitine homeostasis and on response to fasting in children. 151 15

Urinary excretion of 3-phenylpropionylglycine (PPG) is a diagnostic marker for medium-chain acyl-CoA dehydrogenase (MCAD) deficiency. PPG is derived from 3-phenylpropionic acid (PPA), a product of anaerobic bacterial metabolism in the gut. To determine when the infant gut was colonized with PPA-producing bacteria, we cultured stool in prereduced thioglycollate broth from 93 apparently healthy infants. We analyzed the products of bacterial metabolism by gas chromatography/mass spectrometry for the presence of PPA. Trend analysis demonstrated a significant difference (P less than 0.001) in PPA production between early and later infancy. PPA was not detected in 84% of media isolated from stool collected from infants younger than four months. For older infants, 67% of the samples were PPA-positive. Thus, because the normal gut is not sufficiently colonized with PPA-producing bacteria before three to four months of age, PPG analysis alone is not a sensitive marker for the early detection of MCAD deficiency. Using stable isotope dilution mass spectrometry, we measured PPG and n-hexanoylglycine (HG) excretion in two well newborns with MCAD deficiency. HG, believed to be an endogenous metabolite associated with MCAD deficiency, was consistently above normal in all urine samples.
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PMID:When do gut flora in the newborn produce 3-phenylpropionic acid? Implications for early diagnosis of medium-chain acyl-CoA dehydrogenase deficiency. 154 Oct 11

The activity of medium-chain acyl-CoA dehydrogenase (MCAD) with octanoyl-CoA as a substrate was measured in human lymphocytes by a gas chromatographic technique. Phenazine methosulfate was used as the primary electron acceptor. After the addition of crotonase and subsequent hydrolysis, the reaction product 3-hydroxyoctanoic acid was quantitated by capillary gas-liquid chromatography of the trimethylsilyl derivatives. Control subjects had MCAD activities of 3.46 +/- 0.18 nmol/mg protein/min (n = 15). Five patients were investigated while receiving no therapy at all; MCAD activity ranged from 0.08 to 0.23 in four of them and was 0.65 in the fifth one. Subsequent to the long-term administration of 50-150 mg/d of riboflavin to MCAD-deficient patients (n = 11), these activities increased to an average of 0.41 in 10 patients and 2.22 in one. The activities in 15 obligate heterozygotes were 1.91 +/- 0.41 nmol/mg protein/min, thus enabling a clear distinction from controls. Neither heterozygotes nor a control responded to riboflavin. The method was also applicable to postmortem liver tissue. One patient, who had died suddenly and unexpectedly at the age of 19 mo, was correctly diagnosed as MCAD-deficient, whereas five additional children who died of the sudden infant death syndrome showed normal activities.
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PMID:Diagnosis of medium-chain acyl-CoA dehydrogenase deficiency in lymphocytes and liver by a gas chromatographic method: the effect of oral riboflavin supplementation. 159 28

RFLP haplotypes in the region containing the medium-chain acyl-CoA dehydrogenase (MCAD) gene on chromosome 1 have been determined in patients with MCAD deficiency. The RFLPs were detected after digestion of patient DNA with the enzymes BanII. PstI and TaqI and with an MCAD cDNA-clone as a probe. Of 32 disease-causing alleles studied, 31 possessed the previously published A----G point-mutation at position 985 of the cDNA. This mutation has been shown to result in inactivity of the MCAD enzyme. In at least 30 of the 31 alleles carrying this G985 mutation a specific RFLP haplotype was present. In contrast, the same haplotype was present in only 23% of normal alleles (P less than or equal to 3.4 x 10(-18)). These findings are consistent with the existence of a pronounced founder effect, possibly combined with biological and/or sampling selection.
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PMID:The most common mutation causing medium-chain acyl-CoA dehydrogenase deficiency is strongly associated with a particular haplotype in the region of the gene. 167 31

A mutation involving an A-to-G nucleotide replacement at position 985 of the medium-chain acyl-CoA dehydrogenase (MCAD) cDNA was found in homozygous form in 18 unrelated MCAD-deficient families and in heterozygous form in 4 families. By PCR amplification and sequencing of cDNA from a compound heterozygote, we have detected a new mutation in an MCAD-deficient patient in whom one MCAD allele produces mRNA that is missing 4 bp in the MCAD cDNA, while the other allele carries the A-to-G-985 mutation. The presence of this 4-bp deletion was confirmed in the patient's genomic DNA by dot-blot hybridization with allele-specific oligonucleotide probes and by restriction analysis of PCR products. A rapid screening test for this 4-bp deletion was developed, based on mismatched primer PCR amplification. The deletion created a new restrictive-enzyme site which yielded two DNA fragments. The 4-bp deletion was not found in the three remaining MCAD chromosomes not harboring the A-to-G-985 mutation, nor it was present in 20 chromosomes from 10 unrelated normal Caucasians. The PCR-based method for screening these two mutations can detect over 93% of all MCAD mutations.
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PMID:Identification of a new mutation in medium-chain acyl-CoA dehydrogenase (MCAD) deficiency. 172 90

In recent years an increasing number of inherited diseases in man have been identified in which there is an impairment in mitochondrial fatty acid oxidation. Diagnosis is usually done by gas-chromatographic analysis of urine, which may give difficulties, since urinary abnormalities may only be present intermittently. We therefore studied whether leukocytes could be used to study mitochondrial beta-oxidation directly. The results described herein show that leukocytes are able to beta-oxidize octanoate and palmitate. Furthermore, clear abnormalities in octanoate beta-oxidation were found in leukocytes from patients with an established deficiency of medium-chain acyl-CoA dehydrogenase, suggesting that measurement of octanoate and palmitate beta-oxidation in leukocytes may contribute to rapid diagnosis of medium-chain acyl-CoA dehydrogenase deficiency and presumably other mitochondrial beta-oxidation disorders.
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PMID:Fatty acid beta-oxidation in leukocytes from control subjects and medium-chain acyl-CoA dehydrogenase deficient patients. 173 72

The medium-chain acyl-CoA dehydrogenase (MCAD) deficiency of mitochondrial beta oxidation has been identified in a nine-year old boy with a very bland course and easy fatigue as the main symptom. Repeated low frequency stimulation test and EMG for excluding a myasthenia gravis, and screening for urinary organic acid excretion were helpful for the diagnosis. The EMG test at the m. trapezius by stimulation of the n. accessorius showed an extreme decrease of muscle power down to 49%. After i.v. injection of Edrophonium the loss of power of 20% was still significant, so that we could exclude a myasthenia gravis, but we had found signs of a generalised defect in cell chemistry. The diagnosis could be confirmed by a positive 3-phenylpropionic acid-test and moleculargenetic proof of the Adenine to Guanine mutation at position 985 in the MCAD cDNA (G985) with the polymerase chain reaction. The incidence of this organic aciduria is probably 1:60,000 in Germany, but with more attention to this disease and diagnosis of cases with bland courses the incidence will be higher. The MCAD-defect should be considered in the differential diagnosis of patients with Reye syndrome-like encephalopathies, non-ketotic hypoglycaemia or sudden unexpected deaths in infancy.
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PMID:[Acyl coenzyme A dehydrogenase deficiency of medium-chain fatty acids in a 9-year-old boy with adymia. A rare mitochondrial cytopathy which may be more common than previously assumed]. 177 46

Plasma concentrations of octanoate and cis-4-decenoate were measured by gas chromatography-mass spectrometry in children with deficiencies of medium-chain acyl-CoA dehydrogenase (MCAD), long-chain 3-hydroxyacyl-CoA dehydrogenase (3LHAD) and multiple acyl-CoA dehydrogenase (MAD) deficiency. Children receiving medium- and long-chain lipid supplements were also studied. Octanoate was elevated in all but one of the children with MCAD deficiency, in MAD deficiency and in children receiving medium-chain triglyceride supplementation. Cis-4-decenoate was only elevated in MCAD and MAD deficiency. It is concluded that measurement of plasma cis-4-decenoate provides a sensitive and specific test for defects of medium-chain acyl CoA dehydrogenase.
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PMID:Rapid diagnosis of medium-chain acyl CoA dehydrogenase deficiency by measurement of cis-4-decenoic acid in plasma. 177 11

A patient with riboflavin-responsive mild multiple acyl-CoA dehydrogenation deficiency of the ethylmalonic--adipic aciduria type experienced a recurrence of spontaneous hypoglycaemic episodes whilst being given supplementary L-carnitine. This phenomenon is explicable in terms of the known biochemical features of this condition and suggests caution in the carnitine supplementation of patients with defective oxidation of medium- or short-chain fatty acyl-CoA esters. This patient excreted excessive phenylpropionylglycine after an oral phenylpropionic acid load. Thus the phenylpropionic acid loading test is not completely specific for primary medium-chain acyl-CoA dehydrogenase deficiency as has been supposed.
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PMID:Possible deleterious effect of L-carnitine supplementation in a patient with mild multiple acyl-CoA dehydrogenation deficiency (ethylmalonic-adipic aciduria). 177 16


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