Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.1.1.17 (ornithine decarboxylase)
 6,351 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Relationships between ornithine decarboxylase (ODC) and adenosine diphosphate ribosyl transferase (ADPRT) in human mononuclear leukocytes (HML) were tested by statistical comparisons of their values in a group of 46 people, and by use of inhibitors of ADPRT. 2. ODC was assayed following exposure of HML, for 20 hr, to mitogens [phytohemagglutinin (PHA) and pokeweed mitogen]; ADPRT was measured following exposure of HML to H2O2 (100 microM) for 1 hr (activated ADPRT), and in parallel cultures without H2O2 (constitutive ADPRT). 3. Significant correlations were found between ODC and ADPRT values; the effects of smoking disturbed the correlations. PHA induction of ODC was negatively influenced by age (standardized beta coefficient = -2.95, P = 0.005), while age also influenced ADPRT values negatively in non-smokers (for H2O2 activated ADPRT, standardized beta coefficient = -2.74, P less than 0.008). 4. Inhibitors of ADPRT, nicotinamide, caffeine and benzamide inhibited the induction of ODC by PHA in a concentration-dependent manner, in the range (0.6-10 mM) known to inhibit ADPRT.
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PMID:Mitogenic induction of ornithine decarboxylase in human mononuclear leukocytes: relationships with adenosine diphosphate ribosyltransferase. 213 20

Pharmacological doses of niacin and its analogues were given intraperitoneally to rats with and without coadministration of a hepatocarcinogenic dose of diethylnitrosamine (DEN), and their effects on the induction of ornithine decarboxylase (ODC, EC 4.1.1.17) activity in the rat liver were studied. The induction of ODC activity by DEN was inhibited by 74.3, 85.5, 94.6, 97.6, 72.6 and 55.2% by nicotinamide, nicotinic acid, 3-hydroxymethylpyridine, beta-picoline, pyridine-3-aldehyde and ethylnicotinate respectively. When given alone, these analogues did not induce ODC activity. All these compounds are known to have a niacin effect. DEN-induced ODC activity was also inhibited by 84.0, 93.3, 52.8 and 75.9% by 6-aminonicotinamide, picolinic acid, pyridine-3-sulfonic acid and thionicotinamide, respectively, but, peculiarly, they induced ODC activity by their administration alone. These niacin analogues are known to have anti-niacin effects. Tryptophan, N'-methylnicotinamide and isonicotinic acid hydrazide did not affect the DEN-induced ODC activity but could induce ODC by themselves. Tryptophan belongs to the former group and isonicotinic acid hydrazide to the latter group. The reason for these discrepancies is discussed.
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PMID:Inhibitory effects of niacin and its analogues on induction of ornithine decarboxylase activity by diethylnitrosamine in rat liver. 288 66

The metabolism of vitamin B-6 regenerating rat liver and liver from sham-operated control animals fed either a pyridoxine-sufficient or pyridoxine-deficient was investigated. The pyridoxal phosphate levels in plasma, regenerating liver and control liver were determined as were the activities of three enzymes involved in the metabolism of the vitamin, namely, pyridoxine kinase, pyridoxine phosphate oxidase, and pyridoxine phosphate phosphatase. In addition, total and holo-ornithine decarboxylase activities in the livers were measured. The results indicate that the metabolism of vitamin B-6 regenerating rat liver is different from that observed in Morris hepatomas (Thanassi et al. (1981) J. Biol. Chem. 256, 3370-3375). Vitamin B-6 metabolism in Morris hepatomas is concluded to be characteristic of the tumors rather than a property common to rapidly proliferating hepatic tissue. Regenerating liver ornithine decarboxylase holoenzyme activity in pyridoxine deprived rats was maintained at the same level as that in regenerating liver of pyridoxine-sufficient animals. The mechanism behind this maintenance of holo-enzyme activity appears to involve a pronounced increase in the amount of apoornithine decarboxylase. The time-dependent peak of ornithine decarboxylase activity following partial hepatectomy was shifted from four hours to twelve hours by vitamin B-6 deficiency.
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PMID:Vitamin B-6 metabolism and its relation to ornithine decarboxylase activity in regenerating rat liver. 627 18

Induction of cytosolic L-ornithine decarboxylase (ODC) activity in cultures of Friend erythroleukemia cells by seeding in fresh medium was suppressed by treatment with several differentiation inducers. The levels of suppression after 3 h treatment were about 60% at 20 mM nicotinamide, 30% at 1.5% dimethyl sulfoxide (DMSO), and 20% at 5 mM hexamethylene bisacetamide (HMBA). Tracer experiments using [3H]ornithine to determine newly accumulated polyamines including putrescine revealed that the accumulation was suppressed by treatment (18 h) with the inducers. Furthermore, results of polyamine determination by high-pressure liquid chromatography showed that the cellular polyamine content in differentiation-induced cells was lower than those of uninduced cells in early (18 h after inducer treatment) stages of differentiation. Accordingly, it is suggested that cytosolic ODC levels virtually represent the rate of accumulation of intracellular polyamines in the early period of differentiation.
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PMID:Early changes in ornithine decarboxylase activity and polyamines during erythroid differentiation of Friend leukemia cells. 657 60

Nicotinamide (NA), a naturally occurring vitamin and a protease inhibitor, has been shown to be effective in treating some skin ailments. It inhibits cell proliferation and induces cell differentiation. This report shows the effects of NA on mouse skin tumor development and on the critical events involved in this process. NA reduced tumor growth, inhibited the 12-O-tetradecanoylphorbol-13-acetate (TPA) induced ornithine decarboxylase activity, but induced the transglutaminase activity which was inhibited by TPA under different experimental conditions. The effects of NA on ornithine decarboxylase (ODC) and transglutaminase (TG) indicated that nicotinamide (NA) probably programmed the cells for their death in the natural course of time, i.e. programmed cell death. This observation indicates that NA might be a better agent for the detailed study and for the better use in prevention of cancer alone or in combination with other drugs.
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PMID:Effects of nicotinamide on mouse skin tumor development and its mode of action. 1067 81

Vitamin B(6)-dependent enzymes may be grouped into five evolutionarily unrelated families, each having a different fold. Within fold type I enzymes, L-threonine aldolase (L-TA) and fungal alanine racemase (AlaRac) belong to a subgroup of structurally and mechanistically closely related proteins, which specialised during evolution to perform different functions. In a previous study, a comparison of the catalytic properties and active site structures of these enzymes suggested that they have a catalytic apparatus with the same basic features. Recently, recombinant D-threonine aldolases (D-TAs) from two bacterial organisms have been characterised, their predicted amino acid sequences showing no significant similarities to any of the known B(6) enzymes. In the present work, a comparative structural analysis suggests that D-TA has an alpha/beta barrel fold and therefore is a fold type III B(6) enzyme, as eukaryotic ornithine decarboxylase (ODC) and bacterial AlaRac. The presence of both TA and AlaRac in two distinct evolutionary unrelated families represents a novel and interesting example of convergent evolution. The independent emergence of the same catalytic properties in families characterised by completely different folds may have not been determined by chance, but by the similar structural features required to catalyse pyridoxal phosphate-dependent aldolase and racemase reactions.
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PMID:Threonine aldolase and alanine racemase: novel examples of convergent evolution in the superfamily of vitamin B6-dependent enzymes. 1268 35

The mammalian antizyme (AZ) promotes ubiqutin-independent degradation of ornithine decarboxylase, a key enzyme in polyamine biosynthesis. This study shows that AZ suppression in human lung carcinoma A549 cells caused growth defects and death, but made the cells resistant to DNA damaging agents such as gamma-radiation and cisplatin. In these cells, the cellular redox potential (glutathione/glutathione disulfide [GSH/GSSG] ratio) was increased and thus intracellular reactive oxygen species were severely diminished, which might cause growth defects and cell death. The increase of cellular redox potential was mainly caused by dramatic increase of the cytoplasmic nicotinamide adenine dinucleotide phosphate (NADP)(+)-dependent isocitrate dehydrogenase, which generates the reducing equivalents NADPH. In the AZ-suppressed cells, the hypoxia inducible factor 1alpha (HIF-1alpha) was also increased. As in other cases which showed an increment of HIF-1alpha and the cellular redox potential, the AZ-suppressed cells showed resistance to gamma-radiation and anticancer drugs. Therefore, these facts might be considered as important for the use of radio- and chemotherapy on tumor cells which show an unbalance in their polyamine levels.
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PMID:Antizyme suppression leads to an increment of the cellular redox potential and an induction of HIF-1alpha: its involvement in resistance to gamma-radiation. 1848 90

In obesity and type 2 diabetes, Glut4 glucose transporter expression is decreased selectively in adipocytes. Adipose-specific knockout or overexpression of Glut4 alters systemic insulin sensitivity. Here we show, using DNA array analyses, that nicotinamide N-methyltransferase (Nnmt) is the most strongly reciprocally regulated gene when comparing gene expression in white adipose tissue (WAT) from adipose-specific Glut4-knockout or adipose-specific Glut4-overexpressing mice with their respective controls. NNMT methylates nicotinamide (vitamin B3) using S-adenosylmethionine (SAM) as a methyl donor. Nicotinamide is a precursor of NAD(+), an important cofactor linking cellular redox states with energy metabolism. SAM provides propylamine for polyamine biosynthesis and donates a methyl group for histone methylation. Polyamine flux including synthesis, catabolism and excretion, is controlled by the rate-limiting enzymes ornithine decarboxylase (ODC) and spermidine-spermine N(1)-acetyltransferase (SSAT; encoded by Sat1) and by polyamine oxidase (PAO), and has a major role in energy metabolism. We report that NNMT expression is increased in WAT and liver of obese and diabetic mice. Nnmt knockdown in WAT and liver protects against diet-induced obesity by augmenting cellular energy expenditure. NNMT inhibition increases adipose SAM and NAD(+) levels and upregulates ODC and SSAT activity as well as expression, owing to the effects of NNMT on histone H3 lysine 4 methylation in adipose tissue. Direct evidence for increased polyamine flux resulting from NNMT inhibition includes elevated urinary excretion and adipocyte secretion of diacetylspermine, a product of polyamine metabolism. NNMT inhibition in adipocytes increases oxygen consumption in an ODC-, SSAT- and PAO-dependent manner. Thus, NNMT is a novel regulator of histone methylation, polyamine flux and NAD(+)-dependent SIRT1 signalling, and is a unique and attractive target for treating obesity and type 2 diabetes.
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PMID:Nicotinamide N-methyltransferase knockdown protects against diet-induced obesity. 2471 10

Many pathogenic microorganisms have been demonstrated in atherosclerotic plaques and in cerebral plaques in dementia. Hyperhomocysteinemia, which is a risk factor for atherosclerosis and dementia, is caused by dysregulation of methionine metabolism secondary to deficiency of the allosteric regulator, adenosyl methionine. Deficiency of adenosyl methionine results from increased polyamine biosynthesis by infected host cells, causing increased activity of ornithine decarboxylase, decreased nitric oxide and peroxynitrate formation and impaired immune reactions. The down-regulation of oxidative phosphorylation that is observed in aging and dementia is attributed to deficiency of thioretinaco ozonide oxygen complexed with nicotinamide adenine dinucleotide and phosphate, which catalyzes oxidative phosphorylation. Adenosyl methionine biosynthesis is dependent upon thioretinaco ozonide and adenosine triphosphate (ATP), and the deficiency of adenosyl methionine and impaired immune function in aging are attributed to depletion of thioretinaco ozonide from mitochondrial membranes. Allyl sulfides and furanonaphthoquinones protect against oxidative stress and apoptosis by increasing the endogenous production of hydrogen sulfide and by inhibiting electron transfer to the active site of oxidative phosphorylation. Diallyl trisulfide and napabucasin inhibit the signaling by the signal transducer and activator of transcription 3 (Stat3), potentially enhancing immune function by effects on T helper lymphocytes and promotion of apoptosis. Homocysteine promotes endothelial dysfunction and apoptosis by the unfolded protein response and endoplasmic reticulum stress through activation of the N-methyl D-aspartate (NMDA) receptor, causing oxidative stress, calcium influx, apoptosis and endothelial dysfunction. The prevention of atherosclerosis and dementia may be accomplished by a proposed nutritional metabolic homocysteine-lowering protocol which enhances immunity and corrects the altered oxidative metabolism in atherosclerosis and dementia.
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PMID:Hyperhomocysteinemia, Suppressed Immunity, and Altered Oxidative Metabolism Caused by Pathogenic Microbes in Atherosclerosis and Dementia. 2905 5