Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:EXPT00568 (ascorbate)
 23,072 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In stroma-free hemoglobin solution (SFHS) formation of methemoglobin (hemiglobin; Hi) occurs over a period of some months, due to the fact that Hi reduction stops in hemolysates. SFHS should contain active hemoglobin (Hb), which is able to bind oxygen and should not contain inactive Hb (Hi, carboxyhemoglobin) which does not bind oxygen. Reversible binding of oxygen by Hb is only possible when the molecule is in its reduced (Fe++) form. In red blood cells (RBC) Hb is in the reduced form. The formation of Hi, which contains Fe as a result of Hb oxidation, is the first step in Hb degradation. This step is reversible in RBC. Previously, we have described the preparation of SFHS containing the methemoglobin reductase (MR) system of RBC. To improve the stability of SFHS, we first investigated the formation of Hi as a function of pH and ionic strength and quantified the MR activity in SFHS. Non-enzymatic Hi reduction was studied with substances as ascorbate and glutathione. Stimulation of MR by EDTA was tested. Inhibition of Hi formation was studied with nicotinic acid amide in the presence and absence of NADH. It is concluded that ascorbate and glutathione are not effective during extended periods of storage of SFHS, and that EDTA causes formation of large amounts of Hi. Nicotinic acid amide did not inhibit Hi formation. NADH, as a substrate for the MR system, is very effective in keeping Hi low.
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PMID:Quality control material containing hemoglobin for blood gas and pH measurement: improvement of the stability of stroma-free hemoglobin solution. 348 83

The presence of 50 microM t-butyl hydroperoxide induces the oxidation of intramitochondrial pyridine nucleotides and release of accumulated Ca2+ from rat liver but not AS-30D hepatoma mitochondria in the presence of succinate (plus rotenone) as a respiratory substrate. The effects of t-butyl hydroperoxide are mediated by the activities of glutathione peroxidase and reductase, which are less than 20 and 50% as active, respectively, in hepatoma than in normal liver mitochondria. However, the differences in the activities of these enzymes are not responsible for the insensitivity of succinate-energized tumor mitochondria to t-butyl hydroperoxide, since Ca2+ release and pyridine nucleotide oxidation can be elicited when ascorbate plus tetramethyl-p-phenylenediamine are used as alternative respiratory electron donors. In the presence of succinate alone, rat liver mitochondria generate malate exclusively, whereas AS-30D hepatoma mitochondria produce pyruvate and reduced nicotinamide adenine dinucleotide phosphate as well as malate due to the activity of a nicotinamide adenine dinucleotide phosphate-dependent malic enzyme which is not present in normal rat liver mitochondria. These results indicate that the maintenance of pyridine nucleotides in their reduced form by malic enzyme is responsible for the lack of t-butyl hydroperoxide-induced Ca2+ efflux by tumor mitochondria respiring on succinate. This altered pattern of mitochondrial metabolism may also influence the regulation of other reduced nicotinamide adenine dinucleotide phosphate-sensitive activities in addition to that of Ca2+ transport.
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PMID:Hydroperoxide-stimulated release of calcium from rat liver and AS-30D hepatoma mitochondria. 370 77

1. The existing procedures for extraction of oxidized and reduced nicotinamide coenzymes were adapted to spermatozoa to overcome the coenzyme-degrading activity of seminal plasma. 2. The content of total NAD(+) and NADH was determined in the spermatozoa of ram, bull, boar, stallion and cock. NADP(+) and NADPH were not detected in ram spermatozoa. 3. The oxidation state of sperm NAD depended on the seminal plasma, the removal of which produced a change in the percentage oxidation state of the coenzyme, 100x[NAD(+)/(NAD(+)+NADH)], without altering the total content of NAD(+)+NADH. 4. In suspensions of washed ram spermatozoa, incubated anaerobically at 25 degrees C, the percentage oxidation state of NAD declined with increasing spermatozoa concentration. 5. When ram or boar spermatozoa that had been previously washed and resuspended in Ringer phosphate medium, were incubated anaerobically at 25 degrees C with various substances, pronounced effects on the percentage oxidation state of NAD could be observed with l-lactate, pyruvate, oxaloacetate, dihydroxyacetone, formaldehyde and glyceraldehyde; sorbitol and acetoacetate acted only on ram spermatozoa; fructose, glucose, mannose and acetaldehyde acted predominantly on boar spermatozoa. Formaldehyde lowered the (NAD(+)+NADH) content of ram spermatozoa, but none of the other substances had a comparable effect. 6. The percentage oxidation state of sperm NAD was not influenced by exogenous cysteine, cystine, ergothioneine or ascorbate. 7. A highly active sorbitol dehydrogenase could be prepared from ram, but not from boar, spermatozoa. 8. Sorbitol, acetoacetate and 3-hydroxybutyrate effectively supported the respiration of ram, but not boar, spermatozoa. 9. ;Cold shock', resulting from sudden cooling of spermatozoa, abolished motility completely and irreversibly but produced only a slow and partial decrease in the total NAD content. Slight over-heating, sufficient to produce loss of motility, had no adverse effect on the total NAD content. 10. Storage of ram sperm at 14 degrees C produced only a small decrease of NAD after 2 days, but subsequently the loss became greater.
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PMID:Relation between the oxidation state of nicotinamide-adenine dinucleotide and the metabolism of spermatozoa. 414 31

Tryptophan pyrrolase was studied in partially purified extracts of Xanthomonas pruni. The dialyzed enzyme required both heme and ascorbate for maximal activity. Other reducing agents were able to substitute for ascorbate. Protoporphyrin competed with heme for the enzyme, suggesting that the native enzyme is a hemoprotein. The enzyme exhibited sigmoid saturation kinetics. Reduced nicotinamide adenine dinucleotide (NADH), reduced nicotinamide adenine dinucleotide phosphate (NADPH), nicotinic acid mononucleotide, and anthranilic acid enhanced the sigmoid kinetics and presumably bound to allosteric sites on the enzyme. The sigmoid kinetics were diminished in the presence of alpha-methyltryptophan. NAD, NADP, nicotinic acid, nicotinamide, nicotinamide mononucleotide, and several other related compounds were without effect on the activity of the enzyme. These data indicate that the activity of the enzyme is under feedback regulation by the ultimate end products of the pathway leading to NAD biosynthesis, as well as by certain intermediates of this pathway.
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PMID:Regulation of tryptophan pyrrolase activity in Xanthomonas pruni. 424 93

Particles from both Saprospira grandis and Vitreoscilla species, obtained by high-pressure extrusion and sonic treatment, respectively, actively catalyze the oxidation of reduced nicotinamide adenine dinucleotide (NADH) and succinate with O(2). These activities are inhibited by cyanide but not by antimycin; Saprospira is also amytal- and rotenone-insensitive. Vitreoscilla preparations were unable to oxidize mammalian ferrocytochrome c and reduced tetramethyl-p-phenylenediamine, whereas the Saprospira preparations did so actively. Low-temperature (77 K) difference spectroscopy of Vitreoscilla cells and particles indicates the presence of three maxima in the cytochrome alpha-region at 554, 558, and 562 nm. All three cytochromes are active in NADH and succinate oxidation, but none is ascorbate reducible. Cytochrome o is the only CO-binding pigment present and is probably the terminal oxidase; it has properties similar to the cytochrome o isolated in solubilized form from this organism. Saprospira cells and membranes exhibit four cytochrome absorption bands whose maxima are at 550, 554, 558, and 603 nm at 77 K. The latter component has not been noted previously. NADH and succinate reduce all four cytochromes, but ascorbate reduces only the 550- and 603-nm pigments. CO spectra indicate the presence of cytochrome a,a(3) which is probably the oxidase. A second CO-binding pigment is present which is not a peroxidase but may be a cytochrome.
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PMID:Respiratory mechanisms in the Flexibacteriaceae: terminal oxidase systems of Saprospira grandis and Vitreoscilla species. 432 92

The photoreduction of nicotinamide-adenine dinucleotide (NAD(+)), catalyzed by chromatophore fractions from young (1 day) and old (4-5 days) cultures of Rhodospirillum rubrum, was measured in the presence of either succinate or 2,6-dichlorophenol indophenol (DPIP) and an excess of ascorbate. The time-course of photoreduction in the succinate system suggested a "reversed electron flow" from the donor to NAD(+) mediated by a high energy intermediate produced by a light-induced, cyclic electron transport in the chromatophore fractions. The effects of the uncoupler carbonyl cyanide [p-(trifluoromethoxy)phenyl]hydrazone (FCCP) and of the inhibitors antimycin A and 2-heptyl-4-hydroxyquinoline-N-oxide (HQNO) were consistent with this interpretation. The time-course of NAD(+) photoreduction in the presence of DPIP and ascorbate suggested a direct, light-induced electron transport from the donor to the acceptor. We cannot yet distinguish between a model in which the same reaction center is utilized in the photoreduction by both donor systems (the reaction center component P-870 may relate to two primary acceptors at different redox potential levels) and a model in which each photoreducing system is driven by its own reaction center component.
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PMID:The photoreduction of nicotinamide-adenine dinucleotide by chromatophore fractions from Rhodospirillum rubrum. 433 46

Acetate and other short chain n-fatty acids (C(1)-C(6)) inhibit strongly the uptake of l-serine or other l-amino acids but inhibit only weakly that of alpha-methylglucoside or fructose, whether measured in whole cells of Bacillus subtilis or in membrane vesicles that have been energized with reduced nicotinamide adenine dinucleotide (NADH), l-alpha-glycerol phosphate, or ascorbate plus phenazine methosulfate. The acetate inhibition is noncompetitive, as was shown for l-alpha-aminoisobutyric acid uptake by whole cells and for l-serine uptake by membrane vesicles. In membrane preparations, neither NADH oxidation nor the reduction of cytochromes by NADH are affected by fatty acids. All of these effects are similar to those of 2, 4-dinitrophenol. It is concluded that the fatty acids "uncouple" the amino acid carrier proteins from the cytochrome-linked electron transport system (to which they may be coupled via protein interaction or via a cation gradient).
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PMID:Effects of acetate and other short-chain fatty acids on sugar and amino acid uptake of Bacillus subtilis. 434 Aug 66

Oxidative phosphorylation has been demonstrated with mitochondria of the mi-1 respiratory mutant of Neurospora crassa. The P/O ratios observed with these mitochondria were approximately 0.8 with citrate and 0.4 with either externally added reduced nicotinamide adenine dinucleotide (NADH), succinate, or ascorbate-tetramethyl-p-phenylenediamine (TPD). These P/O ratios suggest that there are only two sites of phosphorylation in mitochondria isolated from young (20 to 24 h) cultures of the mi-1 mutant. The energy-dependent reduction of NAD(+) with succinate and the phosphorylation associated with ascorbate-TPD oxidation indicate that the first and the third sites of energy coupling are present in this mutant. Difference spectra of mitochondria from young cultures of the mi-1 mutant revealed the presence of cytochrome c. Cytochromes b and a + a(3) were not detected. However, in the presence of antimycin A, a small peak in the Soret region at 430 nm was observed. A carbon monoxide difference spectrum revealed the presence of a component of the respiratory chain with a spectrum similar to that of cytochrome o. It is of interest that respiratory inhibitors such as antimycin A, 2-n-nonylhydroxyquinoline N-oxide, and cyanide abolished phosphorylation but only partially inhibited oxidation. It is postulated that the mi-1 respiratory system contains two pathways of electron transport-the first is associated with a phosphorylating pathway, whereas the second is a non-phosphorylating electron transport pathway.
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PMID:Studies of respiratory components and oxidative phosphorylation in mitochondria of mi-1 Neurospora crassa. 435 54

Ethanol stimulated the uptake of l-alanine into isolated membrane vesicles of a marine pseudomonad at a rate and to an extent comparable with that obtained with reduced nicotinamide adenine dinucleotide (NADH) or the artificial electron donor ascorbate-N, N, N', N'-tetramethyl-p-phenylenediamine (ascorbate-TMPD). Methanol and branched-chain alcohols had little or no capacity to energize transport. No quantitative relationship was found between the ability of a compound to induce oxygen uptake and to energize transport, since with ethanol initial rates of oxygen uptake were approximately 4% of that obtained with NADH or ascorbate-TMPD. Cytochrome analysis revealed that NADH and ethanol reduced cytochromes b and c, whereas ascorbate-TMPD coupled primarily at the level of cytochrome c. Approximately 25% of the cytochromes reduced by dithionite were reducible by ethanol. Ethanol reduction of both cytochromes b and c was prevented by 2-heptyl-4-hydroxyquinoline-N-oxide, p-chloromercuribenzoate, N-ethylmaleimide, and iodoacetate. The ethanol- and NADH-energized transport systems for l-alanine were subject to quantitatively similar inhibition by cyanide, 2-heptyl-4-hydroxyquinoline-N-oxide, 2, 4-dinitrophenol, and the sulfhydryl reagents p-chloromercuribenzoate, N-ethylmaleimide, and iodoacetate. In contrast, for ascorbate-TMPD-driven transport, only cyanide and 2, 4-dinitrophenol remained fully effective as inhibitors, p-chloromercuribenzoate was only half as effective, and the other compounds stimulated transport. Inhibition of ethanol oxidation strikingly paralleled the inhibition of ethanol-driven transport for each of the inhibitors, including 2, 4-dinitrophenol. Marked differences between inhibition of oxygen uptake and inhibition of transport were observed when NADH or ascorbate-TMPD were the electron donors. The data indicate that only a small proportion of the respiratory chain complexes in the membrane vesicles are involved in transport and these are efficiently coupled to ethanol oxidation. The results also suggest that when 2, 4-dinitrophenol inhibits transport it is not acting as an uncoupling agent.
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PMID:Nature of the specificity of alcohol coupling to L-alanine transport into isolated membrane vesicles of a marine pseudomonad. 436 May 36

The transport of alpha-aminoisobutyric acid and K(+) into K(+)-depleted cells of a marine pseudomonad (ATCC 19855) was stimulated strongly by ethanol, reduced nicotinamide adenine dinucleotide (NADH), and ascorbate-reduced N, N, N', N'-tetramethyl-p-phenylenediamine. In the presence of the quinone inhibitor 2-heptyl-4-hydroxyquinoline-N-oxide, only ascorbate-reduced N, N, N', N'-tetramethyl-p-phenylenediamine was active. Primary and secondary, but not tertiary, alcohols from ethanol to n-amyl alcohol stimulated both alpha-aminoisobutyric acid and K(+) transport and were oxidized by the cells. Malate and succinate, which were oxidized rapidly by the cells, had little or no capacity to energize the transport of alpha-aminoisobutyric acid into K(+)-depleted cells but were partially effective in promoting K(+) uptake. Ethanol stimulated the transport of alpha-aminoisobutyric acid into K(+)-preloaded cells. The transport of both alpha-aminoisobutyric acid and K(+) was inhibited 20% by iodoacetate, 85% by N-ethylmaleimide, and 90 to 100% by both NaCN and p-chloromercuribenzoate. The addition of Na(3)Fe(CN)(6) permitted the ethanol-induced transport of alpha-aminoisobutyric acid into K(+)-preloaded cells in the presence of NaCN, but little or no uptake of alpha-aminoisobutyric acid or of K(+) into K(+)-depleted cells under the same conditions. The transport of alpha-aminoisobutyric acid into K(+)-depleted cells required both K(+) and an electron donor. The oxidation of NADH and ethanol by K(+)-depleted cells was stimulated strongly by K(+). Parallels between these studies and those with membrane vesicles show that results with membrane vesicles of the marine pseudomonad have physiological significance for the intact cells. The results support the conclusion that the energy for the active transport of both alpha-aminoisobutyric acid and K(+) into cells of this organism is provided by electron flow through a region of the respiratory chain lying between cytochrome c and O(2).
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PMID:Specific electron donor-energized transport of alpha-aminoisobutyric acid and K+ into intact cells of a marine pseudomonad. 436 May 37


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