Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “FAD”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 271 records · Page 15Linked to original sources
PubMed1988

High-affinity binding of riboflavin and FAD by immunoglobulins from normal human serum.

The binding of [3H]FAD and [3H]riboflavin to a pooled, human plasma immunoglobulin fraction was studied. For each flavin, the data fit best a model with two binding sites of high affinity and a class of sites of lower affinity. The dissociation constants estimated for the two high affinity sites were 1.73 nM and 0.078 nM for [3H]FAD and 2.43 nM and 0.068 nM for [3H]riboflavin. The results of studies with a series of possible competitors suggested that the flavin ring system was an important determinant of the binding. Other studies showed that the binding reaction was largely enthalpy-driven. Our findings show that normal human immunoglobulins contain one or more species that bind riboflavin and FAD with very high affinity.

Binding Sites↗
PubMed1983

N-demethylation of cocaine to norcocaine. Evidence for participation by cytochrome P-450 and FAD-containing monooxygenase.

Experiments were conducted to determine which microsomal enzymes are involved in the in vitro hepatic oxidative N-demethylation of cocaine to norcocaine, the first step in the biotransformation of cocaine to its ultimate hepatotoxic metabolite. Cocaine was found to undergo conversion to norcocaine by two alternate pathways, one involving only cytochrome P-450 and the other requiring both cytochrome P-450 and FAD-containing monooxygenase. In the first pathway, cocaine was directly N-demethylated to norcocaine by cytochrome P-450; this reaction was enhanced by phenobarbital induction and was inhibited by both n-octylamine and metyrapone. The second route was found to be a two-step reaction involving cocaine N-oxide as an intermediate. In this pathway, cocaine is first oxidized to cocaine N-oxide by FAD-containing monooxygenase, followed by a cytochrome P-450-catalyzed N-demethylation to norcocaine. This latter step was enhanced by phenobarbital treatment and inhibited by n-octylamine. Cocaine N-oxide also exhibited a Type I binding spectrum with mouse hepatic microsomes. In addition, a model system consisting of ferrous sulfate was found to catalyze the N-demethylation of cocaine N-oxide. On the basis of these experiments, it is concluded that cytochrome P-450 and FAD-containing monooxygenase participate in the initial oxidation of cocaine to norcocaine. We also propose a mechanism to account for the conversion of cocaine N-oxide to norcocaine.

Animals↗
PubMedDate not supplied

[Mechanism of action of vitamin B1, thiamine pyrophosphate, and FAD on smooth muscle cells].

The contractile activity of the guinea pig taenia coli longitudinal muscle was studied as affected by exogenic thiamine, thiamine pyrophosphate and FAD. The mentioned substances in a concentration of 1 . 10(-3) M relax the smooth-muscular cells. Against a background of apamine FAD causes a contraction of taenia coli, which is not observed with application of thiaminepyrophosphate. Evidently, there are two, types of receptors sensitive to FAD and one sensitive to vitamin B1 on the membrane of the smooth-muscular cell.

Animals↗
PubMed1980

Transient kinetic study of liver microsomal FAD-containing monooxygenase.

Stopped flow kinetic studies have been used to demonstrate three features of the enzymatic mechanism of the microsomal FAD-containing monooxygenase from hog liver. First, in contrast to the bacterial flavin-containing monooxygenases, reduction of the FAD is independent of substrate. Second, the rate of the reaction of reduced enzyme with oxygen to form the C(4a)-peroxyflavin intermediate is independent of substrate. Third, the rate of transformation of the C(4a)-peroxyflavin to oxidized FAD is substrate-dependent. These results are in agreement with the mechanism, determined by steady state kinetic studies (Poulsen, L.L., and Ziegler, D.M. (1979) J. Biol. Chem. 254, 6449-6455), which predicts that the reduced flavin reacts with oxygen before combination with substrate.

Anaerobiosis↗
PubMed1993

Conformational change and membrane association of the PutA protein are coincident with reduction of its FAD cofactor by proline.

The PutA protein is both the put repressor and a membrane-bound enzyme with proline and delta 1-pyrroline-5-carboxylate dehydrogenase activities. The conditions required for association of purified PutA protein with membrane vesicles suggested that a redox switching mechanism might determine the proportion of PutA protein functioning as a dehydrogenase (Wood, J. M. (1987) Proc. Natl. Acad. Sci. USA 84, 373-377). The FAD cofactor was released from the PutA protein with 1 M KBr at neutral pH. The apoprotein retained delta 1-pyrroline-5-carboxylate dehydrogenase and DNA binding but not proline dehydrogenase activity. Reconstitution with FAD fully restored proline dehydrogenase activity. Proline at a concentration of 0.11 mM caused half-maximal bleaching of the FAD in PutA. Chymotryptic digestion of the PutA protein in the presence and absence of proline demonstrated that the persistence of a 119-kDa protein fragment was characteristic of the reduced protein. Identical digestion patterns were obtained from the apoprotein in the presence and absence of proline. The quantity of the 119-kDa fragment produced varied with proline concentration, yielding a midpoint of 0.056 mM proline. The fraction of PutA protein associated with membrane vesicles was also a function of proline concentration, yielding a titration midpoint of 0.10 mM proline. Membrane binding was thus coincident with both flavin reduction and a change in protein conformation.

Bacterial Proteins↗
PubMed2005

Fad diets and obesity--Part IV: Low-carbohydrate vs. low-fat diets.

The first three parts of this series of articles covered the basics of some of the more popular low-carbohydrate diets, and the theories behind them. In the fourth and final part of this series, some of the more popular low-fat and low-calorie diets, such as the Ornish diet and Weight Watchers, are covered briefly. Recently, several clinical trials of longer duration that compared low-carbohydrate versus low-fat diets have been published. These studies demonstrate that some of the low-carbohydrate diets result in reduced weight in the short-term, but their ability to reduce weight long-term any better than low-fat or other diets has been questioned. Most popular or fad diets have some positive messages contained within them and some preliminary positive short-term results, but overall the compliance rates with any fad diet are very poor over the long-term. The decision to go on any diet should be made with a health professional who can monitor the patient closely.

Body Mass Index↗
PubMed1984

A practical guide to fad diets.

This discussion of fad diets may be concluded by comparing the 14 selected diets with the standards previously outlined for desirable weight reducing plans. Many of the popular diets supply large quantities of saturated fat and cholesterol, which are dietary components that have been associated with cardiovascular disease. Ketogenic diets are not appropriate for athletes because of problems with secondary dehydration and hyponatremia. Almost all of the diets are nutritionally inadequate. The rate of anticipated weight loss will vary according to the age, sex, weight, basal energy requirement, and activity level of an individual. However, it is expected that weight loss will be excessively rapid if a competitive athlete consumes a diet of less than 1000 calories per day. These hypocaloric diets cannot meet the training demands of athletes and will promote loss of lean body mass and carbohydrate stores. Many of the ketogenic diets do not restrict calories; therefore, weight loss will depend upon individual daily caloric consumption. The Cambridge Diet and starvation diets produce weight loss far in excess of that desired for an athlete in training. Long-term eating patterns to maintain weight loss are not encouraged in any of the 14 selected fad diets. In fact, most of these diets promote patterns of poor nutrition. Not one of the diets provides options or choices for dieters to use in accommodating food preference and lifestyle patterns. Some of the diets are fairly easy to comply with and others require special foods and supplements. None of the 14 diets reviewed fulfull all of the standards for a sound weight reduction diet plan.(ABSTRACT TRUNCATED AT 250 WORDS)

Diet Fads↗
PubMed2002

Heterogeneity in fetal akinesia deformation sequence (FADS): autopsy confirmation in three 20-21-week fetuses.

Fetal akinesia deformation sequence (FADS) is a rare condition characterized by intrauterine growth retardation (IUGR), congenital limb contractures, pulmonary hypoplasia, hydramnios and craniofacial abnormalities. The present report comprises an autopsy study of three fetuses to illustrate the variable clinical manifestations and neuropathological findings. Fetus 1 had arthrogryposis and no movement on fetal ultrasound examination. Aborted at 21 weeks, the fetus showed micrognathia, bilateral joint contracture with pterygia at the elbow and axilla. Growth retardation and pulmonary hypoplasia were not major features. Neuropathologic examination revealed anterior horn cell loss and lateral corticospinal tract degeneration in spinal cord, with marked muscular atrophy. Fetus 2, 20 weeks' gestation, had fetal akinesia, nuchal thickening, left pleural effusion, and Dandy-Walker malformation on ultrasound examination. Autopsy showed low-set ears, ocular hypertelorism, cleft palate, flexion contractures with pterygia over axilla, elbow and groin, pulmonary hypoplasia, Dandy-Walker malformation, unremarkable spinal cord and skeletal muscle. Fetus 3, 21 weeks' gestation, was aborted for fetal akinesia, neck and limb webbing and severe arthrogryposis. At autopsy, similar facial abnormalities, contracture and pterygia in neck and multiple major joints were found. Borderline pulmonary hypoplasia and severe lumbar scoliosis were also present. The brain, spinal cord and muscle were unremarkable. In these three fetuses, the prenatal ultrasound and autopsy findings were characteristic of FADS. Neurogenic spinal muscular atrophy was the basis of fetal akinesia in Case 1. Dandy-Walker malformation was present in Case 2, but the pathogenetic mechanism of fetal akinesia was not clear as spinal cord and muscle histology appeared normal. The etiology of akinesia was undetermined in Case 3; no extrinsic or intrinsic cause was identified.

Adult↗
PubMed2000

FAD mutations in presenilin-1 or amyloid precursor protein decrease the efficacy of a gamma-secretase inhibitor: evidence for direct involvement of PS1 in the gamma-secretase cleavage complex.

To investigate the mechanism of regulation of Ass production by familial Alzheimer's disease (FAD)-linked presenilin 1 (PS1), we used a cell-free system that allows de novo Ass generation to examine whether PS1 participates directly in the gamma-secretase reaction. Optimal Ass generation in vitro was achieved at mildly acidic pH and could be inhibited by the aspartyl protease inhibitor pepstatin A, consistent with the suggestion that gamma-secretase is an aspartyl protease. Dominant negative mutations of the critical transmembrane aspartates in PS1 or full deletion of PS1 did not alter the maturation of APP in the secretory pathway. Instead, PS1 had a direct effect on the inhibition of Ass production by a designed peptidomimetic inhibitor: the inhibition was significantly less effective in cells expressing FAD-causing mutations in either APP or PS1 than in cells expressing the wild-type proteins. Taken together, these findings suggest that PS1 participates physically in a complex with APP during the gamma-secretase cleavage event.

Alzheimer Disease↗
PubMed1990

Does FAD-dependent polyamine oxidase contribute to the metabolism of milacemide?

Milacemide, a secondary amine derivative, was previously demonstrated to be a substrate of MAO-B and to be insensitive to the action of copper-dependent amine oxidases. In the present study, it was investigated whether the FAD-dependent secondary amine metabolizing enzyme polyamine oxidase (PAO), could participate in the metabolism of milacemide. For this purpose, the urinary metabolic pattern of oral 14C-milacemide was determined in rats with and without pretreatment with the irreversible PAO inhibitor MDL 72527 and, for comparison, after inhibition of MAO-B by l-deprenyl. While l-deprenyl was shown to significantly decrease the urinary excretion of glycinamide and of an unknown metabolite (UK1), pretreatment with MDL 72527 did not modify the elimination of milacemide as glycinamide but produced a decrease in UK1 equal to that induced by l-deprenyl. The percent of the dose of milacemide eliminated as unchanged drug was slightly but significantly increased after PAO inhibition, though considerably less than after l-deprenyl. These data suggest that milacemide might be a substrate of PAO. If confirmed, this result would constitute the first example of the involvement of the FAD-dependent PAO in drug metabolism.

Acetamides↗
PubMed2005

Changes in FAD and NADH fluorescence in neurosecretory terminals are triggered by calcium entry and by ADP production.

We measured changes in the intrinsic fluorescence (IF) of the neurosecretory terminals of the mouse neurohypophysis during brief (1-2 s) trains of stimuli. With fluorescence excitation at either 350 +/- 20 or 450 +/- 50 nm, and with emission measured, respectively, at 450 +/- 50 or > or = 520 nm, DeltaF/F(o) was approximately 5-8 % for a 2 s train of 30 action potentials. The IF changes lagged the onset of stimulation by approximately 100 ms and were eliminated by 1 microM tetrodotoxin (TTX). The signals were partially inhibited by 500 microM Cd(2+), by substitution of Mg(2+) for Ca(2+), by Ca(2+)-free Ringer's with 0.5 mM EGTA, and by 50 microM ouabain. The IF signals were also sensitive to the mitochondrial metabolic inhibitors CCCP (0.3 microM), FCCP (0.3 microM), and NaN(3) (0.3 mM), and their amplitude reflected the partial pressure of oxygen (pO(2)) in the bath. Resting fluorescence at both 350 nm and 450 nm exhibited significant bleaching. Flavin adenine dinucleotide (FAD) is fluorescent, while its reduced form FADH(2) is relatively non-fluorescent; conversely, NADH is fluorescent, while its oxidized form NAD is non-fluorescent. Thus, our experiments suggest that the stimulus-coupled rise in [Ca(2+)](i) triggers an increase in FAD and NAD as FADH(2) and NADH are oxidized, but that elevation of [Ca(2+)](i), alone cannot account for the totality of changes in intrinsic fluorescence.

Adenosine Diphosphate↗
PubMed2003

Involvement of glycine and aspartate residues in the binding capacity of FAD in the NADH dehydrogenase from an alkaliphilic Bacillus.

There is a region exhibiting a similarity of amino acid sequence near the carboxyl-terminal segment of each FAD-containing oxidoreductase. In this region, four amino acid residues-Thr, Ala, Gly, and Asp-are highly conserved. To determine the involvement of the four amino acid residues (Thr-469, Ala-476, Gly-478, and Asp-479) in the activity of NADH dehydrogenase of an alkaliphilic Bacillus, mutations of these amino acid residues were conducted. In spite of high conservation, mutations of Thr-469 and Ala-476 to Ala and Ser, respectively, did not lead to a critical loss of enzyme activity. However, mutations of Gly-478 and Asp-479 to Ala caused a complete loss of the activity, which appears to result from the loss of binding capacity of FAD.

Aspartic Acid↗
PubMed1990

Identification of FAD, FMN, and riboflavin in the retina by microextraction and high-performance liquid chromatography.

The presence of flavins in the retina has been known for some time. However, the small size of the tissue has made it difficult to quantify the levels of the individual flavins, riboflavin (RB), FMN, and FAD without pooling large numbers of retinas. A procedure to extract and quantitate RB, FMN, and FAD in retinal tissue from as few as four rat retinas has been developed. The procedure resolves these three classes of flavins and provides a recovery near 100%. For the analysis, HPLC using a reverse-phase column with cyclohexyl functional groups was coupled to a fluorescence detector. The microextraction-HPLC procedure was reproducible for the quantitative analysis of flavins in the retina and equally applicable for analysis of flavins in liver and plasma.

Animals↗
PubMed1975

Studies on chicken liver xanthine dehydrogenase with reference to the problem of non-equivalence of FAD moieties.

1. Reduction of chicken liver xanthine dehydrogenase (xanthine: NAD+ oxidoreductase, EC 1.2.1.37) by xanthine under anaerobic condition proceeded in two phases. This biphasicity may be due to functional and non-functional enzymes in the enzyme preparation. 2. Cyanolysis of a persulfide group of chicken liver enzyme resulted in an inactivation of the enzyme. The non-functional enzyme in the standard enzyme preparation was found to lack persulfide groups at the active sites. 3. The remaining NADH-Methylene Blue oxidoreductase activity, after KI treatment of the xanthine-reduced enzyme of a high flavin activity ratio, is not at the level of 50% of the initial activity, differing from the report suggesting non-equivalence of FAD chromophores. 4. The findings in the present report indicate that FAD chromophores of chicken liver enzyme are essentially equivalent.

Animals↗
PubMed1978

FAD-dependent malate dehydrogenase, a phospholipid-requiring enzyme from Mycobacterium sp. strain Takeo. Purification and some properties.

FAD-dependent malate dehydrogenase, a phospholipid-requiring enzyme, was homogeneously purified from the particulate fraction of Mycobacterium sp. strain Takeo. The isolated enzyme contains no FAD and few phospholipid, and has a specific activity of 300-360 units/mg of protein. In the assay system without addition of phospholipid (cardiolipin), the enzyme activity was only about 3% of maximum activity. The molecular weight was estimated to be 51 000-55 000 by four methods. Titration by p-chloromercuribenzoate revealed the presence of one cysteine residue/mol of enzyme. The isoelectric point was found to be pH 6.9 by isoelectric focusing. From circular dichroism spectral data, the enzyme protein was found to contain alpha-helix structure of 24%.

Amino Acids↗
PubMed1983

The role of porcine thyroid peroxidase and FAD-containing monooxygenase in the metabolism of 1-methyl-2-thioimidazole (methimazole).

The peroxidase and FAD-containing monooxygenase activities of porcine thyroid subcellular preparations were measured and it was observed that FAD-containing monooxygenase activity was considerably lower than that of peroxidase. The end product of 1-methyl-2[14C]thioimidazole oxidation catalysed by thyroid peroxidase was confirmed to be 1-methylimidazole by mass spectrometry. In the presence of thyroid peroxidase 1-methyl-2-thioimidazole would appear initially to be oxidised to bis(1-methylimidazole)-2,2'-disulphide. The extent of oxidation was dependent on the iodide concentration in the reaction mixture.

Animals↗
PubMed1983

ESR analysis of the FAD in bovine liver monoamine oxidase.

Two hydrazine spin labels, 1-oxyl-2,2,5,5-tetramethylpyrroline-3-carbonyl ethyl hydrazine and 1-oxyl-2,2,6,6-tetramethylpiperidino-4-hydrazine, were synthesized as probes of the FAD binding site of monoamine oxidase. The reporter nitroxide moiety showed an ESR spectrum classified as partially immobilized which is indicative of FAD near the surface of the enzyme. Attempts to pick up flavin semiquinone or free radical intermediates during substrate oxidation with the spin traps 5,5-dimethyl-1-pyrroline-1-oxidase and phenyl-t-butylnitrone were not successful.

Animals↗
PubMed1985

Metabolism of phosphorus-containing compounds by pig liver microsomal FAD-containing monooxygenase.

Oxidative desulfuration of phosphonate insecticides such as fonofos (S-phenyl ethyl ethylphosphonodithioate) and its analogs is catalyzed by pig liver microsomal FAD-containing monooxygenase, although desulfuration of phosphorodithioates, such as parathion, is not. Substitution of an alkyl group for the remaining alkoxy group, as in S-phenyl diethylphosphinodithioate, did not increase its oxidation rate. Diethylphenylphosphine sulfide, containing 3 phosphorus-carbon bonds, was actually a poorer substrate than fonofos. Replacement of the S-phenyl group of fonofos with an O-phenyl group increased the Km value above the solubility limit. Trivalent phosphorus-containing compounds were also excellent substrates for this enzyme. Diethylphenylphosphine had a Km value lower than 2.5 microM. Diethyl phenylphosphonite also appeared to be an excellent substrate but its rapid nonenzymatic hydrolysis and/or oxidation precluded accurate Km determinations. Stoichiometry studies with diethylphenylphosphine and its sulfide showed that O2 and NADPH consumption were approximately equal to the substrate consumed. The major metabolite of both diethylphenylphosphine and its sulfide was the phosphine oxide. These results show that microsomal FAD-containing monooxygenase of pig liver has activity as a phosphorus-oxidase, in addition to its well characterized nitrogen- and sulfur-oxidase roles.

Animals↗