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 resonance Raman (RR) spectra of FMN, FAD, FAD in D2O, and 7,8-dimethyl-1, 10-ethyleneisoalloxazinium perchlorate have been obtained by employing KI as a collisional fluorescence-quenching agent. The spectra are very similar to those obtained recently by using the CARS technique to eliminate fluorescence. Spectra have also been obtained for several species in which flavin is known to fluoresce only weakly. We report RR spectra of protonated FMN, FMN semiquinone cation, the general fatty acyl-CoA dehydrogenase, and two "charge-transfer" complexes of fatty acyl-CoA dehydrogenase. Tentative assignment of several vibrational bands can be made on the basis of our flavin spectra. RR spectra of fatty acyl-CoA and its complexes are consistent with the previous hypothesis that visible spectral shifts observed during formation of acetoacetyl-CoA and crotonyl-CoA complexes of fatty acyl-CoA dehydrogenase result from charge-transfer interactions in which the ground state is essentially nonbonding as opposed to interactions in which complete electron transfer occurs to form FAD semiquinone. The only significant change in the RR spectrum of FAD on binding to enzyme occurs in the 1250-cm-1 region of the spectrum, a region associated with delta N--H of N-3. The position of this band in fatty acyl-CoA dehydrogenase and the other flavoproteins studied to date is discussed in terms of hydrogen bonding between flavin and protein.
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PMID:Resonance Raman study of flavins and the flavoprotein fatty acyl coenzyme A dehydrogenase. 47 62

As a result of impaired fatty acid oxidation, a characteristic urinary dicarboxylic aciduria occurs in the riboflavin deficient animal. We compared the occurrence of riboflavin deficiency induced by phototherapy with changes in urinary organic acid profiles in 8 full-term, breast-fed neonates who received phototherapy for hyperbilirubinemia, and in 10 full-term, breastfed controls. Riboflavin status was assessed by measuring flavin adenine dinucleotide saturation of erythrocyte glutathione reductase. All 8 neonates exposed to phototherapy developed riboflavin deficiency (p less than 0.001). Riboflavin deficiency was progressive with the duration of phototherapy. None of the controls was riboflavin deficient. Urine organic acid profiles indicative of mitochondrial acyl-CoA dehydrogenase activity (fatty acid beta-oxidation, quantitated by gas chromatography mass spectrometry) showed no changes between the study and control groups in mono-, di-, or tricarboxylic acids or other organic acids. The riboflavin deficiency induced by phototherapy in full-term neonates was not of sufficient severity to limit riboflavin-dependent fatty acid oxidation.
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PMID:Significance of phototherapy-induced riboflavin deficiency in the full-term neonate. 156 34

8-Thiocyanatoflavins at the riboflavin, FMN, and FAD level were prepared via the diazonium salt of the corresponding 8-aminoflavin and some of the physical and chemical properties studied. 8-Thiocyanatoriboflavin has a UV-visible spectrum similar to that of the native flavin with absorbance maxima at 446 nm (epsilon = 14,900 M-1 cm-1) and 360 nm. Reaction with thiols such as dithiothreitol and mercaptoethanol gives rise to an 8-mercapto- and an 8-SR-flavin, whereas reaction with sulfide yields only the 8-mercaptoflavin. The 8-SCN-flavin binds to riboflavin-binding protein as the riboflavin derivative, to apoflavodoxin, apo-Old Yellow Enzyme, and apo-lactate oxidase as the FMN derivative, and to apo-D-amino acid oxidase, apo-p-hydroxybenzoate hydroxylase, apo-glucose oxidase, apo-anthranilate hydroxylase, and apo-general acyl-CoA dehydrogenase as the FAD derivative. In two cases, namely, with anthranilate hydroxylase and D-amino acid oxidase, the 8-SCN-FAD was spontaneously and completely converted to the 8-mercapto-FAD derivative, suggesting the presence of a nucleophile (most likely the thiol of a cysteine residue) in the vicinity of the 8-position. It was also found that flavodoxin stabilizes the neutral radical and Old Yellow Enzyme the anionic radical of 8-SCN-FMN. Further studies with Old Yellow Enzyme, established that fully (two electron) reduced 8-SCN-FMN undergoes photoelimination of cyanide.
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PMID:8-thiocyanatoflavins as active-site probes for flavoproteins. 167 Sep 91

The 19F NMR spectra of the oxidized and reduced forms of 8-fluororiboflavin, 8-fluoro-FAD, and the 8-fluoroflavin-reconstituted flavoproteins flavodoxin, riboflavin binding protein, D-amino acid oxidase, p-hydroxybenzoate hydroxylase, Old Yellow Enzyme, anthranilate hydroxylase, general acyl-CoA dehydrogenase, glucose oxidase, and L-lactate oxidase were measured. For the proteins studied the oxidized resonances appeared over a 10.1-ppm range, while the reduced resonances were spread over 10.3 ppm. Reduction caused an upfield shift of about 27 ppm for the free 8-fluoroflavins and most of the 8-fluoro flavoproteins. The notable exception was 8-fluoro-FMN flavodoxin, which was shifted 37.6 ppm, indicating an unusually high electron density in the benzene ring. Ligand binding to the oxidized 8-fluoro flavoproteins caused either upfield or downfield shifts of 1.5-5 ppm, depending on the protein/ligand combination. The 8-fluoro-FAD anthranilate hydroxylase resonance was shifted downfield and split into two peaks in the presence of anthranilate. The 8-fluoro-FMN Old Yellow Enzyme resonance was shifted upfield upon complexation with charge-transfer-forming, para-substituted phenolates. The upfield shift increased from less than 1 to 5 ppm as the electron-donating capacity of the phenolate increased. Complexation of native Old Yellow Enzyme with 2,4-difluorophenol caused the fluorine resonances of the ligand to shift and split into two pairs of signals. Each pair of signals was associated with a different isozyme of Old Yellow Enzyme.
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PMID:19F NMR studies on 8-fluoroflavins and 8-fluoro flavoproteins. 197 65

Riboflavin-deficient rats are used to study the metabolism of deuterium-labeled nonanoic acids under conditions mimicking the human disorder of multiple acyl-CoA dehydrogenase deficiency in which large amounts of ethyl-malonic, glutaric, adipic, suberic, 4-octenedioic, sebacic and 4-decenedioic acids are excreted. Both control and deficient rats convert the nonanoic acids to labeled azelaic and pimelic acids. The labeling pattern in pimelic acid is consistent with the omega-oxidation of nonanoic acids to azelaic acid followed by beta-oxidation to pimelic acid.
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PMID:Metabolism of deuterium-labeled nonanoic acids in the riboflavin-deficient rat model of multiple acyl-CoA dehydrogenase deficiency. 205 91

The 8-demethyl-8-hydroxy-5-deaza-5-carba analogues of FMN and FAD have been synthesized. Several apoproteins of flavoenzymes were successfully reconstituted with these analogues. This and further tests established that these analogues could serve as general probes for flavin stereospecificity in enzyme-catalyzed reactions. The method used by us involved stereoselective introduction of label on one enzyme combined with transfer to and analysis on a second enzyme. Using as a reference glutathione reductase from human erythrocytes for which the absolute stereochemistry of catalysis is known from X-ray studies [Pai, E. F., & Schulz, G. E. (1983) J. Biol. Chem. 258, 1752-1758], we were able to determine the absolute stereospecificities of other flavoenzymes. We found that glutathione reductase (NADPH), general acyl-CoA dehydrogenase (acyl-CoA), mercuric reductase (NADPH), thioredoxin reductase (NADPH), p-hydroxybenzoate hydroxylase (NADPH), melilotate hydroxylase (NADH), anthranilate hydroxylase (NADPH), and glucose oxidase (glucose) all use the re face of the flavin ring when interacting with the substrates given in parentheses.
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PMID:Absolute stereochemistry of flavins in enzyme-catalyzed reactions. 380 93

Seven infants in one kindred died: one was stillborn; the others, who were floppy at birth and were breast-fed, developed a disorder with the odor of sweaty feet and died in early infancy. In two further pregnancies, 3-hydroxvisovaleric, glutaric, and C6-C10-dicarboxylic acids were demonstrated in the mother's urine during the seventh month. Riboflavin therapy in the last trimester of pregnancy and a riboflavin-rich diet given the infants prevented this syndrome. The presence of abnormal erythrocyte glutathione-reductase activity in the mother while she excreted normal amounts of riboflavin in her urine indicates a probable disorder of riboflavin metabolism resulting in multiple acyl-CoA dehydrogenase deficiency.
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PMID:Multiple acyl-CoA dehydrogenase deficiency occurring in pregnancy and caused by a defect in riboflavin metabolism in the mother. Study of a kindred with seven deaths in infancy: Value of riboflavin therapy in preventing this syndrome. 688 4

We studied the role of FAD in the intramitochondrial folding and assembly of medium-chain acyl-CoA dehydrogenase (MCAD), a homotetrameric mitochondrial enzyme containing a molecule of non-covalently bound FAD/monomer. In the MCAD molecule, FAD is buried in a crevice containing the active center. We have previously shown that upon import into mitochondria, newly processed MCAD is first incorporated into a high molecular weight (hMr) complex and that the hMr complex mainly consisted of MCAD-heat-shock protein 60 (hsp60) complex (Saijo, T., Welch, W.J., and Tanaka, K (1994) J. Biol. Chem. 269, 4401-4408). In the present study, we incubated in vitro synthesized precursor MCAD with mitochondria isolated from normal and riboflavin-deficient rat liver for 10-60 min and fractionated the solubilized mitochondria using gel filtration. The amount of MCAD in the hMr complex was larger and that of tetramer was smaller in riboflavin-deficient mitochondria than in control at any time point. In addition, riboflavin-deficient mitochondria were solubilized after 10-min import in a buffer containing ATP and were chased in the presence of FAD, FMN, or NAD+ or without any addition. The mitochondrial proteins were analyzed using gel filtration or immunoprecipitated with anti-hsp60 antibody. After 60-min chase in the presence of FAD, the majority of MCAD in the complex with hsp60 was transferred to tetramer, whereas no such transfer occurred after the chase in the absence of FAD. When chase was done in the presence of FMN, a significant amount of MCAD was transferred from the complex with hsp60 to tetramer, but the transfer was not as efficient as in the presence of FAD. The chase in the presence of NAD+ resulted in no transfer. These data suggest that isoalloxazine ring of FAD plays a critical role, exerting nucleating effect, in the hsp60-assisted folding of MCAD subunit into an assembly competent conformation, probably assisting the formation of the core.
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PMID:Isoalloxazine ring of FAD is required for the formation of the core in the Hsp60-assisted folding of medium chain acyl-CoA dehydrogenase subunit into the assembly competent conformation in mitochondria. 782 28

A 62-year-old man was admitted to our hospital because of easy fatigability of the lower limbs during walking. The biopsied muscle specimen showed excessive lipid accumulation. The carnitine concentration in the muscle was at the lower level of the normal range. Organic acid urinalysis was consistent with the diagnosis of multiple acyl-CoA dehydrogenase deficiency or glutaric acidemia type II. In cultured lymphoblastoid cells from this patient there was impaired beta-oxidation, but the activities of acyl-CoA dehydrogenases were normal. Riboflavin therapy resulted in a dramatic improvement in both clinical and biochemical aspects. In this patient, the defect in coenzyme binding to electron transfer flavoprotein (ETF) or ETF-dehydrogenase was suspected. In the adult case of lipid storage myopathy, multiple acyl-CoA dehydrogenase deficiency should be suspected as one of its pathogenesis and riboflavin therapy should be considered.
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PMID:A riboflavin-responsive lipid storage myopathy due to multiple acyl-CoA dehydrogenase deficiency: an adult case. 785 27

The 13C- and 15N-NMR spectra of porcine kidney medium-chain acyl-CoA dehydrogenase (MCAD) reconstituted with 13C- and 15N-enriched FADs were measured. The positions of selective enrichment were C(2), C(4), C(4 alpha), C(10 alpha), N(1), N(3), and N(5) of the isoalloxazine nucleus of FAD. The NMR signals of the labeled atoms were observed as broad but distinct peaks in each NMR spectrum. The chemical shift values of the 2-, 4-, 4 alpha-, and 10 alpha-13C for the oxidized form of MCAD were 159.5, 166.8, 141.1, and 155.5 ppm, respectively, relative to the methyl resonance of 3-(trimethylsilyl)propionic acid-d4, while those of 1-, 3-, and 5-15N for the oxidized form were 183.6, 161.1, and 334.7 ppm, relative to liquid ammonia, respectively. The upfield shift of 2-13C of MCAD relative to that of FMN in the aqueous medium and its downfield shift relative to that of tetraacetylriboflavin in an apolar medium imply that a weaker hydrogen bond exists between C(2) = O and apoMCAD or a water molecule than that of free FMN with a water molecule. That the 4-13C resonance was observed downfield-shifted relative to that of free FMN in aqueous solution suggests a strong hydrogen bond between C(4) = O and apoMCAD. The chemical shift for 4 alpha-13C in oxidized MCAD is considerably downfield-shifted from that of FMN or any other flavoprotein observed thus far, indicating a unique environment around this position in MCAD. The 1-15N resonance of MCAD was most upfield-shifted among the flavoproteins observed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:13C- and 15N-NMR studies on medium-chain acyl-CoA dehydrogenase reconstituted with 13C- and 15N-enriched flavin adenine dinucleotide. 845 67


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