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)

Neoplasms affecting different subsections of the large bowel appear to have different risk factors. For the major type of neoplastic disease in the large bowel, that in the descending and sigmoid colon, a good association with nutrition and specific nutritional elements has been found. The risk of this type of colon cancer is proportional to the customary dietary fat intake--high in the Western World and low in the Orient. It is inversely proportional to stool bulk, which is itself modulated by cereal fibre intake. Fat and fibre, as the two major elements implicated, are sufficiently secure with regard to underlying scientific data and understanding of mechanisms, to permit utilising them to modify risk. Thus, a dietary regimen low in total fat, 20% of calories, and higher in cereal fibre, of the order of 30 grams/day, is indicated. Such a modified nutritional intake could be expected to reduce risk, not only in the general population, but most likely also in patients who have been treated successfully by conventional means. Additional evidence suggests that regular intake of yellow and green vegetables, of foods containing calcium salts, selenium and other micro-nutrients, lower the risk even more. More research is needed to provide the data necessary for deliberate intervention with these agents. Gastric cancer, on the other hand, has a distinct set of risk factors, namely, intake of pickled and salted fish or beans. Other risk factors are associated with residence in areas where the geochemical or agricultural sources of nitrate intake are not balanced by the presence of vitamin C, vitamin E, or certain phenolic antioxidants and nitrite traps such as pyrogallol, tannins, or peptides. The possible genotoxic carcinogen is not yet known, but it could be an alkyl-nitrosamide type of aryldiazonium chemical. The formation of such compounds is inhibited by vitamin C, vitamin E, and certain antioxidants. This fact can be used to decrease deliberately the risk of gastric cancer.
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PMID:Human and laboratory studies on the causes and prevention of gastrointestinal cancer. 609 59

1. The cytochrome type of the particulate fraction from cells of Alcaligenes sp. was examined. The particulate fraction of aerobically-grown cells contained b-, c-, a-type and o-type like cytochromes, whereas that from nitrate-grown cells contained b-, c-type and o-type like cytochromes. 2. Two kinds of c-type cytochromes were extracted and purified from the particulate fraction of nitrate-grown cells of Alcaligenes sp. One of them showed absorption maxima at 415.5, 522, and 551 nm is the reduced form, and at 410.5 nm in the oxidized form; the other at 417.5, 523, and 556 nm in the reduced form, and at 412 nm in the oxidized form; these cytochromes were designated cytochrome c-551 and cytochrome c-556, respectively. 3. Cytochrome c-551 had a molecular weight of 28,800 and had two heme groups per molcule. The midpoint oxidation reduction potential at pH 7.0 (Em, 7) was +262 mV. Cytochrome c-556 had a molecular weight of 18,200 and contained one heme group per molecule. The Em, 7 value was +291 mV. These cytochromes were not autoxidizable, did not react with carbon monoxide or KCN at pH 7.0, and were reduced by ascorbate. 4. Each cytochrome acts to some degree as electron carrier in the dissimilatory nitrite reduction reaction of Alcaligenes sp.
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PMID:Components of the cytochrome system of Alcaligenes sp. N.C.I.B., 11015, with special reference to particulate bound c-type cytochromes. 624 4

Campylobacter sputorum subspecies bubulus contains a membrane-bound nitrite reductase which catalyses the six-electron reduction of nitrite to ammonia. Formate and L-lactate are used as hydrogen donors. Cells of C. sputorum grown with nitrate or nitrite contain cytochromes of the b- and c-type and a carbon monoxide-binding cytochrome c. In addition, a special membrane-bound carbon monoxide-binding pigment is found. Nitrite reduction with formate or L-lactate as a hydrogen donor is strongly inhibited by 2-n-heptyl-4-hydroxyquinoline-N-oxide (HQNO). Nitrite reduction by bacterial suspensions with lactate as a hydrogen donor is strongly inhibited by carbonylcyanide-m-chlorophenylhydrazone (CCCP) whereas nitrite reduction with formate as a hydrogen donor is not inhibited at all. Leads to H+/O values and leads to H+/NO-2 values were measured with ascorbate + N,N,N',N'-tetramethyl-p-phenylenediamine (TMPD), formate (in the absence and presence of carbonic anhydrase) and L-lactate as a hydrogen donor. The results are summarized in a scheme for electron transport from formate or lactate to oxygen or nitrite which shows a periplasmic orientation of formate dehydrogenase and nitrite reductase and a cytoplasmic orientation of lactate dehydrogenase and oxygen reduction, and which shows proton translocation with a leads to H+/2e value of 2.0. The leads to H+/O and leads to H+/NO-2 values predicted by this scheme are in good agreement with the experimental values.
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PMID:Electron transport-linked proton translocation at nitrite reduction in Campylobacter sputorum subspecies bubulus. 628 Jun 34

Possible etiological factors involved in oesophageal cancer in various parts of the world and in certain provinces in Northern China are summarized. Evidence is accumulating that N-nitroso compounds and their precursors are involved in the disease in Northern China, as shown in a recent study: excretion of urinary N-nitrosamino acids by inhabitants living in a high- (Linxian) and in a low-risk area (Fanxian) for oesophageal cancer was compared. Linxian subjects excreted significantly more nitrate and nitrosamino acids (N-nitrosoproline, N-nitrosothiazolidine-4-carboxylic acid, N-nitrososarcosine) than those in Fanxian. When Linxian subjects were given 100 mg vitamin C three times a day (after each meal) together with proline, the level of urinary N-nitrosamino acids was reduced to that found in Fanxian. Thus, vitamin C, an efficient inhibitor of endogenous nitrosation, should now be examined in intervention trials in subjects in whom endogenous formation of N-nitroso compounds is elevated.
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PMID:Recent studies on N-nitroso compounds as possible etiological factors in oesophageal cancer. 653 80

The metabolic fate of a p.o. dose of 3.5 mmol 15N-labeled nitrate has been investigated in 12 healthy young adults. Samples of urine, saliva, plasma, and feces were collected over a period of 48 hr following administration of the dose. Subjects received either 60 mg of ascorbic acid, 2 g of ascorbic acid, or 2 g of sodium ascorbate per day. An average of 60% of the 15NO3- dose appeared in the urine as nitrate within 48 hr. Less than 0.1% appeared in the feces. The 15N label of nitrate was also found in the urine (3%) and feces (0.2%) in the form of ammonia or urea. The fate of the remaining 35% of the 15NO3- dose administered is unknown. No effect of ascorbic acid or sodium ascorbate on the nitrate and nitrite levels of plasma, saliva, urine, or feces was observed. A one-compartment pharmacokinetic model was used to describe the relationships between intake, plasma concentration, and urinary excretion of nitrate. The half-life of nitrate in the body was found to be approximately 5 hr, and its volume of distribution was about 30% of body weight. Daily endogenous biosynthesis of nitrate was estimated to be about 1 mmol/day.
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PMID:Metabolic fate of an oral dose of 15N-labeled nitrate in humans: effect of diet supplementation with ascorbic acid. 683 27

The use of safranine, a positively-charged dye, as a probe for the determination of membrane potentials in Escherichia coli vesicles has been studied. 1. Shifts in the spectrum of safranine were observed during induction of potassium ion diffusion potentials with valinomycin or during oxidation of formate by vesicles prepared from cells of E. coli K-12 or ML 308-225 subjected to anaerobic growth with nitrate. The extent of the valinomycin-dependent spectral change correlated linearly with the magnitude of the K+ equilibrium potential, as calculated from the Nernst equation, from 50 to 160 mV (interior negative). The formate-induced changes could also be calibrated by increasing the concentration of potassium in the presence of valinomycin, after the formation of formate-dependent responses. In this case, results identical to those obtained with the first method were obtained. 2. O2 or nitrate-dependent oxidation of formate resulted in a membrane potential of the order of 170 mV. The oxidation of ascorbate-reduced N-methylphenazonium methosulphate resulted in a potential of similar magnitude, but anaerobically with nitrate only a small but definite potential was formed. 3. The water-soluble quinones, duroquinone and menadione, could produce membrane potentials when used in their oxidized or reduced forms in the presence of formate or nitrate (or oxygen). 2-Hydroxy-1,4-naphthoquinone was not only ineffective but was found to be inhibitory. 4. N,N'-dicyclohexylcarbodiimide at suitable concentrations increased the rate of formation and the extent of membrane potentials induced by respiration or by artificial means.
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PMID:Measurements of membrane potentials in Escherichia coli K-12 inner membrane vesicles with the safranine method. 698 99

Indoleamine 2,3-dioxygenase (IDO) and nitric oxide synthase are part of the anti-tumor and antimicrobial activities of mononuclear phagocytes induced by interferon-gamma (IFN gamma). As IDO is a heme-containing enzyme and NO, the product of nitric oxide synthase-initiated arginine degradation, is a regulator of heme enzymes, we investigated whether NO is capable of modulating IDO activity in IFN gamma-primed mononuclear phagocytes. Authentic NO gas or the NO-generating compound, diethylamine dinitric oxide adduct, dose-dependently inhibited IDO activity in cell lysates prepared from IFN gamma-primed human peripheral blood mononuclear cells, as assessed by the ascorbate/methylene blue assay for IDO. In contrast, neither nitrite nor nitrate affected IDO activity. Exposure of intact IFN gamma-primed human peripheral blood mononuclear cells or monocyte-derived macrophages to any of the NO-generating compounds, sodium nitroprusside, glyceryl trinitrate, S-nitroso-N-acetylpenicillamine, or diethylamine dinitric oxide adduct, resulted in inhibition of both the consumption of tryptophan from and formation of its metabolite, kynurenine, in the culture medium. The observed inhibition of IDO activity was not due to toxicity of the NO generators and was abrogated by the co-addition of oxyhemoglobin, an antagonist of NO function. Comparable concentrations of nitrite or nitrate did not inhibit IDO activity in intact cells. In contrast to human cells, addition of IFN gamma to murine macrophages, cultured in complete RPMI 1640 medium, readily induced nitric oxide synthase. Others have reported that such treatment does not induce IDO activity in these cells. However, induction of IDO activity was observed in murine macrophages when the synthesis of reactive nitrogen species was inhibited, by using arginine-free medium and/or the nitric oxide synthesis inhibitor, NG-monomethyl-L-arginine. Together, these results demonstrate that both exogenous and endogenous NO inhibit IDO activity and that oxidative arginine and tryptophan metabolism in IFN gamma-primed mononuclear phagocytes are functionally related. Our study thereby provides an insight into how these cells may regulate some of their antimicrobial and anti-tumor activities.
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PMID:Nitric oxide inhibits indoleamine 2,3-dioxygenase activity in interferon-gamma primed mononuclear phagocytes. 751 70

A new mechanism is presented for the oxidation of ascorbate by peroxynitrite. Our mechanism involves the reaction of ascorbate both with ground-state peroxynitrous acid (HOONO) and with a reactive intermediate (HOONO*); the reactive intermediate is postulated to be formed in the decay of HOONO to form nitrate. At physiological pH, the ascorbate monoanion (AH-) is the predominant ascorbate species. The plot of the observed rate constant for peroxynitrite decay (kobs) vs AH- for the reaction of peroxynitrite with AH- shows two regions, one linear and one curved. In the linear region, which involves high AH- concentrations, the reaction is dominated by the bimolecular reaction between HOONO and AH-. At lower AH- concentrations, this bimolecular reaction slows and reactions with both HOONO and HOONO* produce the observed curvature. Analysis of the data leads to the estimation of the ratio of rate constants for the reaction of AH- with HOONO* (k2*) and the decay of HOONO to nitrate (kN), giving the value of k2*/kN = 3158 +/- 505 M-1; and of the rate constant (k2) for the reaction between AH- and HOONO, k2 = 236 +/- 14 M-1 s-1. Ascorbate displays higher selectivity for HOONO* than does methionine or 2-keto-4-thiomethylbutanoic acid, two substrates whose reactivity toward HOONO and HOONO* has previously been reported. The biological relevance of the reaction of ascorbate with peroxynitrite is discussed in terms of the rate constants and the concentrations of AH- typically found in biological systems; ascorbate may react with HOONO*, although the reaction with ground-state HOONO probably is too slow to occur in vivo.
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PMID:Stopped-flow kinetic study of the reaction of ascorbic acid with peroxynitrite. 757 94

The questions of whether and how N-nitroso compounds (NOC) may be inducing cancer in humans are discussed. The principal subjects covered include nitrite-derived alkylating agents that are not NOC, reasons for the wide tissue specificity of carcinogenesis by NOC, the acute toxicity of nitrosamines in humans, mechanisms of in vivo formation of NOC by chemical and bacterial nitrosation in the stomach and via nitric oxide (NO) formation during inflammation, studies on nitrite esters, use of the nitrosoproline test to follow human gastric nitrosation, correlations of nitrate in food and water with in vivo nitrosation and the inhibition of gastric nitrosation by vitamin C and polyphenols. Evidence that specific cancers are caused by NOC is reviewed for cancer of the stomach, esophagus, nasopharynx, urinary bladder in bilharzia and colon. I review the occurrence of nitrosamines in tobacco products, nitrite-cured meat (which might be linked with childhood leukemia and brain cancer) and other foods, and in drugs and industrial situations. Finally, I discuss clues from mutations in ras and p53 genes in human tumors about whether NOC are etiologic agents and draw some general conclusions.
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PMID:Role of N-nitroso compounds (NOC) and N-nitrosation in etiology of gastric, esophageal, nasopharyngeal and bladder cancer and contribution to cancer of known exposures to NOC. 760 May 41

Twenty two lines/accessions belonging to 5 species of Celosia were analysed for their nutritional and antinutritional composition. The nutrient contents, vitamin C varied from 18.8 to 53.6 mg/100 g, carotenoids 9.1 to 15.1 mg/100g, protein 2.1 to 5.9%, while the antinutritional factors, nitrate 0.18 to 0.46% and oxalate 0.98 to 3.93%. Moisture ranged 81 to 89%. Variation of these parameters with leaf position and the amino acids profile of some promising lines was also evaluated.
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PMID:Composition and variation in vitamin C, carotenoids, protein, nitrate and oxalate contents in Celosia leaves. 765 99


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