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Query: KEGG:D02011 (FAD)
 5,530 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been demonstrated that perfusion of myocardium with glutamic acid or tricarboxylic acid cycle intermediates during hypoxia or ischemia, improves cardiac function, increases ATP levels, and stimulates succinate production. In this study isolated adult rat heart cells were used to investigate the mechanism of anaerobic succinate formation and examine beneficial effects attributed to ATP generated by this pathway. Myocytes incubated for 60 min under hypoxic conditions showed a slight loss of ATP from an initial value of 21 +/- 1 nmol/mg protein, a decline of CP from 42 to 17 nmol/mg protein and a fourfold increase in lactic acid production to 1.8 +/- 0.2 mumol/mg protein/h. These metabolite contents were not altered by the addition of malate and 2-oxoglutarate to the incubation medium nor were differences in cell viability observed; however, succinate release was substantially accelerated to 241 +/- 53 nmol/mg protein. Incubation of cells with [U-14C]malate or [2-U-14C]oxoglutarate indicates that succinate is formed directly from malate but not from 2-oxoglutarate. Moreover, anaerobic succinate formation was rotenone sensitive. We conclude that malate reduction to succinate occurs via the reverse action of succinate dehydrogenase in a coupled reaction where NADH is oxidized (and FAD reduced) and ADP is phosphorylated. Furthermore, by transaminating with aspartate to produce oxaloacetate, 2-oxoglutarate stimulates cytosolic malic dehydrogenase activity, whereby malate is formed and NADH is oxidized. In the form of malate, reducing equivalents and substrate are transported into the mitochondria where they are utilized for succinate synthesis.
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PMID:Evidence for succinate production by reduction of fumarate during hypoxia in isolated adult rat heart cells. 342 43

1. The alpha-hydroxylation of [1-14C]phytanic acid was investigated in the postnuclear fraction of rat liver. 2. The reaction required ATP, Mg, Fe3+ and molecular oxygen. Fe3+ could be replaced by Fe2+. 3. The hydroxylase activity was optimal at pH 7.5 in phosphate buffer. 4. The activity increased with postnuclear protein (5-13 mg or protein), increased with the substrate concentration at low substrate concentration. 5. The amount of the hydroxyacid formed increased with time up to 10 min. 6. Coenzyme A (100 microM-2.5 mM) stimulated the activity. 7. The activity was further stimulated by NADP and NADPH slightly and by FAD and FMN strongly, all at 100 microM concentration. 8. While CO inhibited the reaction, phenobarbital inducible cytochrome P-450 did not appear to play a role in this reaction.
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PMID:Phytanic acid alpha oxidation in rat liver: studies on alpha hydroxylation. 362 98

The oxidation of [1-14C]lignoceric acid was studied in different subcellular fractions of rat brain. The highest specific activity for oxidation of [1-14C]lignoceric acid to acetate was observed in the light mitochondrial fraction. The oxidation of [1-14C]lignoceric acid had an absolute requirement for CoASH and ATP. It was stimulated by NAD and FAD by 400 and 280 percent, respectively, whereas addition of carnitine and KCN had no effect. These properties suggest that in brain [1-14C]lignoceric acid is oxidized in peroxisomes.
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PMID:Peroxisomal oxidation of lignoceric acid in rat brain. 370 6

Evidence is presented that peroxisomes are more important than other subcellular fractions in rat liver for the final reactions in the biosynthesis of cholic acid from cholesterol. The peroxisomal conversion of 3 alpha, 7 alpha, 12 alpha-trihydroxy-5 beta-cholestanoic acid (THCA) into cholic acid was studied in detail and optimal assay conditions were defined. It was shown that the reaction involves intermediary formation of 3 alpha, 7 alpha, 12 alpha, 24-tetrahydroxy-5 beta-cholestanoic acid and that ATP, CoA, Mg++, NAD+ and FAD are necessary. With use of 18O2 and 2H2O it was further shown that the introduction of the 24-hydroxyl group in 3 alpha, 7 alpha, 12 alpha, 24 alpha-tetrahydroxy-5 beta-cholestanoic acid is the combined result of a desaturase and a hydratase. The reaction mechanism is thus analogous to that for beta-oxidation of fatty acids. The role of peroxisomes under conditions in vivo was studied in three patients with the rare inborn cerebro-hepato-renal syndrome of Zellweger. Apparently infants with this fatal disease have a complete lack of peroxisomes in the liver and kidneys. The patients were found to accumulate THCA and various polar metabolites of THCA in serum and bile. Administration of two 3H-labelled C27-precursors to bile acids (5 beta-cholestane-3 alpha, 7 alpha, 12 alpha-triol and 7 alpha-hydroxy-4-cholesten-3-one) resulted in a rapid conversion into THCA and a subsequent slow conversion into cholic acid. Administration of 3H-labelled THCA resulted in a slow conversion into cholic acid.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of peroxisomes in the biosynthesis of bile acids. 386 45

Acid nucleotide pyrophosphatase was isolated from the cell-free extracts of Pichia guilliermondii Wickerham ATCC 9058. The enzyme was 25-fold purified by saturation with ammonium sulphate, gel-filtration on Sephadex G-150 column and ion-exchange chromatography on DEAE-Sephadex A-50 column. The pH optimum was 5.9, temperature optimum--45 degrees C. The enzyme catalyzed the hydrolysis of FAD, NAD+ and NADH, displaying the highest activity with NAD+. The Km, values for FAD, NAD+ and NADH were 1.3 x 10(-5) and 2.9 x 10(-4) M, respectively. The hydrolysis of FAD was inhibited by AMP, ATP, GTP, NAD+ and NADP+. The K1 for AMP was 6.6 x 10(-5) M, for ATP--2.0 X 10(-5) M, for GTP--2.3 X 10(-6) M, for NAD+--1.7 X 10(-4) M. The molecular weight of the enzyme was 136 000 as estimated by gel-filtration on Sephadex G-150 and 142 000 as estimated by thin-layer gel-filtration chromatography on Sephadex G-200 (superfine). Protein-bound FAD of glucose oxidase was not hydrolyzed by acid nucleotide pyrophosphatase. The enzyme was stable at 2 degrees C in 0.05 M tris-maleate buffer, pH 6.2. Alkaline nucleotide pyrophosphatase hydrolyzing FAD was also detected in the cells of P. guilliermondii.
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PMID:[Purification and properties of the Pichia guilliermondii acid nucleotide pyrophosphatase hydrolyzing flavin adeninine dinucleotide]. 610 93

Alkaline nucleotide pyrophosphatase was isolated from the Pichia guilliermondii Wickerham ATCC 9058 cell-free extracts. The enzyme was 740-fold purified by saturation of ammonium sulphate, gel-chromatography on Sephadex G-150 and ion-exchange chromatography on DEAE-cellulose. Nucleotide pyrophosphatase is the most active at pH 8.3 and 49 degrees C. The enzyme catalyzes the hydrolysis of FAD, NAD+, NADH, NADPH, GTP. The Km value for FAD is 2.4 x 10(-4) M and for NAD+--5.7 x 10(-6) M. The hydrolysis of FAD was inhibited by NAD+, NADP+, ATP, AMP, GTP, PPi and Pi. The Ki for NAD+, AMP and Na4P2O7 was 1.7 x 10(-4) M, 1.1 x 10(-4) M and 5 x 10(-5) M, respectively. Metal chelating compounds, 8-oxyquinoline, o-phenanthroline and EDTA, inhibited completely the enzyme activity. The EDTA effect was irreversible. The molecular weight of the enzyme determined by gel-filtration on Sephadex G-150 and thin-layer gel-filtration chromatography was 78000 dalton. Protein-bound FAD of glucose oxidase is not hydrolyzed by the alkaline nucleotide pyrophosphatase. The enzyme is stable at 2 degrees C in 0.01 M tris-HCl-buffer (pH 7.5).
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PMID:[Purification and properties of Pichia guilliermondii yeast alkaline nucleotide pyrophosphatase hydrolyzing flavin adenine dinucleotide]. 611 Nov 46

The effect of riboflavin status on hepatic activities of the relatively substrate-specific flavokinase and FAD synthetase and the relatively nonspecific FMN phosphatase and FAD pyrophosphatase was investigated in weanling, male Sprague-Dawley rats fed 0, 5, 15, 30 and 60 micrograms riboflavin/15 g diet for 1, 3 and 5 weeks. Flavokinase activity was determined by using [14C]riboflavin and ATP as substrates and measuring product [14C]FMN after incubation and separation by high performance liquid chromatography. Similarly, FAD synthetase activity was determined by using [3H]ATP and FMN and quantitating [3H]FAD formed. Flavokinase activities among all groups were similar after only 1 week of feeding experimental diets; by 3 weeks, activities were depressed to about 60% of normal in animals that received suboptimal riboflavin; by 5 weeks, activity of rats fed riboflavin-free diet was further decreased to about 40% of normal. FAD synthetase activities were unaffected by riboflavin status at 1 and 3 weeks; however, at 5 weeks, activities were moderately decreased to 85, 65 and 52% of normal with rats which had received 15, 5 and 0 microgram riboflavin/15 g diet, respectively. FMN phosphatase and FAD pyrophosphatase activities decreased with age, but were not influenced by riboflavin status at any period. Overall results indicate the effect of increasing severity of riboflavin deficiency is greater with flavokinase, which is physiologically rate-limiting in the biosynthesis of flavocoenzymes, than with FAD synthetase.
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PMID:Effect of riboflavin status on hepatic activities of flavin-metabolizing enzymes in rats. 613 98

Two components of the histidine permease in Salmonella typhimurium, the membrane-bound P and M proteins, react with the photoaffinity labeling reagent 8-azido-ATP in isolated membranes. The extent of labeling is decreased by the addition of ATP and somewhat less by addition of GTP, CTP, UTP, and ADP. Cyclic AMP, NAD, FAD, and S-adenosylmethionine have little effect. We propose that one or both of these proteins have a site capable of binding an adenine nucleotide and that, therefore, they may be involved in the energy-coupling step in active transport.
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PMID:ATP-binding sites in the membrane components of histidine permease, a periplasmic transport system. 623 89

Flavokinase (ATP:riboflavin 5'-phosphotransferase, EC 2.7.1.26) has been purified to apparent homogeneity from rat liver by affinity chromatography using flavinyl agarose beads (agarose-OCH2CONH(CH2)2NHCO(CH2)/N10-7,8-dimethylisoalloxazine). The specific activity of the pure enzyme is 9,900 units (nmol of FMN formed/h at 37 degrees C)/mg of protein, and reflects a one-step, 7000-fold purification. Flavokinase thus obtained, unlike previous preparations from mammalian sources, is free from contaminating phosphatase and FAD synthase. The purified enzyme rapidly loses activity upon storage but is stabilized by riboflavin and thiol-protecting reagents. The apparent molecular weight, estimated by gel filtration on Sephadex G-100 and sodium dodecyl sulfate-polyacrylamide gel electrophoresis, is 28,000 +/- 1,000. Flavokinase phosphorylates and/or is inhibited by a large number of riboflavin analogs; however, the physiologically important 8 alpha-(amino acid)riboflavins are poorly accommodated. The strongly preferred phosphate donors are ATP and dATP. Both Zn2+ and Mg2+, as well as several other divalent cations, activate flavokinase, but Zn2+ yields greatest activity (1.8 times that with Mg2+). The pH optimum for activity with either Zn2+ or Mg2+ is approximately 9.3; at pH 7.0, the activity is 40% of that at the pH optimum.
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PMID:Affinity chromatographic purification and properties of flavokinase (ATP:riboflavin 5'-phosphotransferase) from rat liver. 624 35

Three distinct enzymes hydrolyzing either ApppA or AppppA, or both, were separated and purified from yellow lupin seed extracts. Two of the enzymes were purified to homogeneity. These enzymes differ greatly in their catalytic and physical properties. One hydrolase, with a native molecular weight of 41,000, exhibits broad pH (from 5-8) optimum for activity, requires Mg2+ for activity, is inhibited by zinc ions (I0.5 = 25 microM) and hydrolyses ApppA (V = 1), ApppC (V = 0.38), ApppG (V = 0.2), and ribose(5')pppA (V = 0.2). The enzyme exhibits much lower activity with AppppA (V = 0.1), and ApppppA, AppppppA, ppppA, and ATP are hydrolyzed 25- to 100-fold slower then ApppA. ADP was always one of the products of the reactions catalyzed by the enzyme. AppA, NAD, NADP, FAD, cAMP, and p-nitrophenyl-thymidine 5'-phosphate were not hydrolyzed by the enzyme. The enzyme is diadenosine 5',5"'-P1, P3-triphosphatase. The second hydrolase, composed of one polypeptide chain of a molecular weight 18,000-18,500, exhibits optimal activity in the pH range from 7.5-9, requires Mg2+ for activity, is inhibited by calcium ions (I0.5 for calcium depends on the concentration of Mg2+ and is 35-180 microM in the presence of 0.5-10 mM Mg2+, respectively), and hydrolyzes AppppA (V = 1, Km = 1 microM), ApppppA (V = 0.42, Km = 1.8 microM), AppppppA (V = 0.34), AppppU (V = 0.73), AppppC (V = 0.67), AppppG (V = 0.27), and ppppA. ATP was always one of the products of the reactions catalyzed by the enzyme. Dinucleoside di- and triphosphates, ATP, cAMP, and p-nitrophenylthymidine 5'-phosphate were not hydrolyzed by the enzyme. This enzyme is diadenosine 5',5"'-P1,P4-tetraphosphatase (EC 3.6.1.17). The third hydrolase, composed of one polypeptide chain of a molecular weight of 56,000, exhibits maximal activity at pH 9-10.5, does not require Mg2+ ions for activity, is inhibited neither by divalent cations (Mg2+, Ca2+, Zn2+, Co2+, Mn2+, or Ni2+) nor by EDTA, and uses as substrates all compounds which are substrates for the diadenosine 5',5"'-P1,P3-triphosphatase and diadenosine 5',5"'-P1,P4-tetraphosphatase. In addition, the enzyme hydrolyzes p-nitrophenyl-thymidine 5'-phosphate, p-nitrophenylthymidine 3'-phosphate, bis-p-nitrophenylphosphate, ADP, AppA, NAD, NADP, and FAD, but not cAMP. With the exception of p-nitrophenylphosphate derivatives all other substrates of the enzyme yield AMP as one of the products of hydrolysis. This enzyme has a specificity similar to that of phosphodiesterases (EC 3.1.4.1) from other sources. With the lupin phosphodiesterase, ApppA (V = 1, Km = 2.2 microM) and AppppA (V = 1, Km = 2.0 microM) are better substrates than NAD (V = 0.8, Km = 9.6 microM), AppA (V = 0.4), ApppppA (V = 0.6), and AppppppA (V = 0.34).
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PMID:Enzymes hydrolyzing ApppA and/or AppppA in higher plants. Purification and some properties of diadenosine triphosphatase, diadenosine tetraphosphatase, and phosphodiesterase from yellow lupin (Lupinus luteus) seeds. 630 93


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