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At least 19 recordsLinked to original sources
PubMed1990

Deaminated neuraminic acid-rich glycoprotein of rainbow trout egg vitelline envelope. Occurrence of a novel alpha-2,8-linked oligo(deaminated neuraminic acid) structure in O-linked glycan chains.

Deaminated neuraminic acid-rich glycoprotein (KDN-gp), first found and isolated from the vitelline envelope of rainbow trout eggs (Inoue, S., Kanamori, A., Kitajima, K., and Inoue, Y. (1988) Biochem. Biophys. Res. Commun. 153, 172-176), has been found to contain a number of O-linked glycan. Oligosaccharides were released by alkaline borohydride treatment of KDN-gp. Following fractionation by DEAE-Sephadex A-25 and thin-layer chromatography, a series of acidic oligosaccharides were obtained and analyzed for their chemical structures. The structure is based on composition analysis, methylation analysis, alkali-catalyzed "peeling" reactions, periodate oxidation, 400-MHz one- and two-dimensional 1H NMR spectroscopy, and molecular secondary ion mass spectrometry. The O-linked oligosaccharides isolated from KDN-gp have been shown to contain a common core trisaccharide Gal beta 1-3GalNAc alpha 1-3GalNAc in which the terminal Gal residue is blocked by a single residue of deaminated neuraminic acid (KDN) and the proximal GalNAc residue is substituted by alpha-2,8-linked oligo(KDN) chains. Structures of KDN-oligosaccharide chains in the glycoprotein are novel and expressed by the following general formula, where n = 0-5, for which data are available. [formula: see text]

Animals↗
PubMed1984

[Deamination and reductive deamination of (2-amino-5, 6-dimethylbenzimidazolyl)cobamide. Preparation of (2-hydroxy-5, 6-dimethylbenzimidazolyl)cobamide and (5, 6-dimethyl-[2(-14)C]-benzimidazolyl)cobamide].

(2-Amino-5, 6-dimethylbenzimidazolyl)-cobamide (III) is transformed to (2-hydroxy-5, 6-dimethylbenzimidazolyl) cobamide (IV) by nitrous acid. Exchange of the NH2-group by hydrogen with nitrous acid/hypophosphorous acid yields vitamin B12 (I). This reaction completes a cycle vitamin B12 (I)----[carboxy(2-cyanoamino-4,5-dimethylphenyl)amino]cobamide+ ++ (II)----(2-amino-5,6-dimethylbenzimidazolyl)cobamide (III)----vitamin B12 (I), which allows chemical 14C-labelling of vitamin B12. In this procedure cyanogen bromide, which is necessary for the first step, was labelled with [14C] cyanide. By the following reactions a vitamin B12 was formed in which C-2 of the 5, 6-dimethylbenzimidazole moiety is labelled.

Chemical Phenomena↗
PubMed1990

A sensitive genetic assay for the detection of cytosine deamination: determination of rate constants and the activation energy.

Previously it has not been possible to determine the rate of deamination of cytosine in DNA at 37 degrees C because this reaction occurs so slowly. We describe here a sensitive genetic assay to measure the rate of cytosine deamination in DNA at a single cytosine residue. The assay is based on reversion of a mutant in the lacZ alpha gene coding sequence of bacteriophage M13mp2 and employs ung- bacterial strains lacking the enzyme uracil glycosylase. The assay is sufficiently sensitive to allow us to detect, at a given site, a single deamination event occurring with a background frequency as low as 1 in 200,000. With this assay, we determined cytosine deamination rate constants in single-stranded DNA at temperatures ranging from 30 to 90 degrees C and then calculated that the activation energy for cytosine deamination in single-stranded DNA is 28 +/- 1 kcal/mol. At 80 degrees C, deamination rate constants at six sites varied by less than a factor of 3. At 37 degrees C, the cytosine deamination rate constants for single- and double-stranded DNA at pH 7.4 are 1 x 10(-10) and about 7 x 10(-13) per second, respectively. (In other words, the measured half-life for cytosine in single-stranded DNA at 37 degrees C is ca. 200 years, while in double-stranded DNA it is on the order of 30,000 years.) Thus, cytosine is deaminated approximately 140-fold more slowly when present in the double helix. These and other data indicate that the rate of deamination is strongly dependent upon DNA structure and the degree of protonation of the cytosine. The data suggest that agents which perturb DNA structure or facilitate direct protonation of cytosine may induce deamination at biologically significant rates. The assay provides a means to directly test the hypothesis.

Bacteriophages↗
PubMed1976

Ontogenesis of enzyme systems deaminating different monoamines.

1 A detailed investigation into the postnatal development of the activity of the enzyme monoamine oxidase (MAO) in the rat and domestic pig was carried out. 2 MAO activity was measured in littermate male rats aged between 3 and 122 days belonging to six breeding colonies. The tissues studied were three brain regions in which monoamines may play a role in neuronal transmission (septum, hypothalamus, corpus striatum) and, for comparison, in the cerebellum. Liver, heart and adrenal glands were the peripheral organs studied. The following substrates were used to measure MAO activity in each tissue homogenate: kynuramine, tyramine, dopamine, tryptamine and 5-hydroxytryptamine (5-HT). 3 MAO activity towards kynuramine, tyramine and dopamine increased after birth in all brain regions and also in the liver, to reach maximal values between days 40 and 80. In the heart and the adrenal glands enzyme activity remained low up to 30-40 days and then increased steeply. This was the case in all litters examined. 4 All tissues deaminated more tyramine than dopamine. In the liver, the ratio of the quantities of tyramine deaminated/dopamine deaminated was approx. 2 at all ages. In the homogenates of whole brains (including or excluding the hypothalamus and striatum) this ratio was also 2 at all ages. In contrast in the isolated striatum and hypothalamus it was first much higher and reached a value of 2 only at an age of about 20 days. This may indicate an independent development of a dopamine and a tyramine deaminating enzyme system in discrete brain regions. It was suggested, that the low ability to deaminate dopamine in discrete brain regions may be due to the local presence of an enzyme inhibitor which becomes too diluted to be active in homogenates of whole brain. 5 Deamination of tryptamine in the striatum decreased between day 5 and 20 in 3 out of 4 colonies tested. There was a large fall in the deamination of 5-HT in all tissues of one group of rats, but in another 4 groups the tissues of the 5 day old rats deaminated smaller amounts of 5-HT than those of the older rats. 6 Purified hypothalamic mitochondria from 40 day old rats deaminated more tyramine and dopamine but not tryptamine per mg protein than those from 5 day old rats. 7 In the domestic pig there was a significant rise in the values in hippocampal MAO activity towards dopamine and tyramine from the foetus (55 day gestation) to the 1 week old piglet. A further steady rise up to week 6 was indicated, but this rise was not statistically significant. The difference between rat and pig probably reflected the much higher degree of maturity of the latter at birth. 8 In the hippocampus of the pig the ratio between the amount of tyramine deaminated/dopamine deaminated decreased from greater than 10 (foetus) to 4.8 in the 6 week old pig and 2 in the adult.

Age Factors↗
PubMed1993

Cytosine deamination in mismatched base pairs.

The rate of deamination of cytosine in mismatched base pairs has been determined. Incubation of M13mp2 nicked heteroduplex DNA molecules containing T.C or C.C mispairs in the lacZ alpha-complementation gene results in deamination of cytosine to uracil, producing T.U or C.U mispairs. Strands which have undergone deamination at the target site to produce uracil will yield dark blue plaque revertants, while all other strands yield faint blue or colorless plaque phenotypes upon transfection of an ung- alpha-complementation Escherichia coli host strain. Rate constants were calculated from the reversion frequencies for several different heteroduplexes incubated at either 60 or 37 degrees C. For the 60 degrees C incubations, the hydrolytic deamination rate constants for mispairs in three different local sequence environments ranged from 8 x 10(-10) to 40 x 10(-10) s-1. For incubations at 37 degrees C, the rate constants were between 0.4 x 10(-10) and 1.3 x 10(-10) sec-1. At both temperatures and for all mispairs, these rate constants are significantly greater than deamination rate constants in properly matched Watson-Crick G.C base pairs and are similar to those constants determined for cytosine deamination in single-stranded DNA. Since deamination most likely occurs via a single-stranded intermediate, the data suggest that, at 37 degrees C, the T.C and C.C mispairs exhibit from 20% to 100% single-stranded character. We conclude that cytosine residues involved in a mispair in DNA are 1-2 orders of magnitude more prone to deaminate to uracil than are cytosines in double-stranded DNA.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacteriophage M13↗
PubMed1998

Enzyme-mediated cytosine deamination by the bacterial methyltransferase M.MspI.

Most prokaryotic (cytosine-5)-DNA methyltransferases increase the frequency of deamination at the cytosine targeted for methylation in vitro in the absence of the cofactor S-adenosylmethionine (AdoMet) or the reaction product S-adenosylhomocysteine (AdoHcy). We show here that, under the same in vitro conditions, the prokaryotic methyltransferase, M.MspI (from Moraxella sp.), causes very few cytosine deaminations, suggesting a mechanism in which M.MspI may avoid enzyme-mediated cytosine deamination. Two analogues of AdoMet, sinefungin and 5'-amino-5'-deoxyadenosine, greatly increased the frequency of cytosine deamination mediated by M.MspI presumably by introducing a proton-donating amino group into the catalytic centre, thus facilitating the formation of an unstable enzyme-dihydrocytosine intermediate and hydrolytic deamination. Interestingly, two naturally occurring analogues, adenosine and 5'-methylthio-5'-deoxyadenosine, which do not contain a proton-donating amino group, also weakly increased the deamination frequency by M.MspI, even in the presence of AdoMet or AdoHcy. These analogues may trigger a conformational change in the enzyme without completely inhibiting the access of solvent water to the catalytic centre, thus allowing hydrolytic deamination of the enzyme-dihydrocytosine intermediate. Under normal physiological conditions the enzymes M.HpaII (from Haemophilus parainfluenzae), M. HhaI (from Haemophilus hemolytica) and M.MspI all increased the in vivo deamination frequency at the target cytosines with comparable efficiency.

Adenosine↗
PubMed1998

Nitric oxide-induced deamination of cytosine and guanine in deoxynucleosides and oligonucleotides.

The autoxidation of nitric oxide (NO.) forms the nitrosating agent N2O3, which can directly damage DNA by deamination of DNA bases following nitrosation of their primary amine functionalities. Within the G:C base pair, deamination results in the formation of xanthine and uracil, respectively. To determine the effect of DNA structure on the deamination of guanine and cytosine, the NO.-induced deamination rate constants for deoxynucleosides, single- and double-stranded oligonucleotides, and a G-quartet oligonucleotide were measured. Deamination rate constants were determined relative to morpholine using a Silastic membrane to deliver NO. at a rate of approximately 10-20 nmol/ml/min for 60 min, yielding a final concentration of approximately 600-1200 microM NO2-. GC/MS analysis revealed formation of nanomolar levels of deamination products from millimolar concentrations of deoxynucleosides and oligomers. Deamination rate constants for cytosine and guanine in all types of DNA were lower than the morpholine nitrosation rate constant by a factor of approximately 10(3)-10(4). Xanthine was formed at twice the rate of uracil, and this may have important consequences for mechanisms of NO.-induced mutations. Single-stranded oligomers were 5 times more reactive than deoxynucleosides toward N2O3. Double-stranded oligomers were 10-fold less reactive than single-stranded oligomers, suggesting that Watson-Crick base pairing protects DNA from deamination. G-quartet structures were also protective, presumably because of hydrogen bonding. These results demonstrate that DNA structure is an important factor in determining the reactivity of DNA bases with NO.-derived species.

Cytosine↗
PubMed1981

Correlation between glutamate deamination and glutamine deamidation in rat kidney mitochondria.

Intramitochondrial glutamate removal through deamination may regulate renal ammoniagenesis from glutamine. However, little information is available to determine if there is a strong association between glutamine deamidation and the removal within mitochondria of the glutamate subsequently formed after deamidation. Using rat renal mitochondria, we found that ammonia production, glutamate appearance, and amide nitrogen disappearance were near equal aerobically and anerobically, when no ADP-generating system was present. When an ADP-generating system was added (ATP alone, ATP+ malonate, or ATP+2,4 DNP), more ammonia was formed aerobically from glutamine. Additionally, less glutamate appeared even though more amide nitrogen disappeared. Intramitochondrial concentrations of glutamate decreased. When pyruvate and alpha-ketoglutarate were added to the system, ammoniagenesis, deamidation, and deamination decreased; while glutamate built up in both the medium and mitochondria. In our mitochondrial system, we found a significantly positive correlation between glutamate deamination and glutamine deamidation, between glutamate accumulation and intramitochondrial glutamate concentrations; and a significantly negative correlation between glutamate deamination and glutamate accumulation, between glutamine deamidation and intramitochondrial glutamate concentrations, and between glutamate deamination and glutamate accumulation. We conclude that there is a biochemical relationship between glutamine deamidation and deamination of the glutamate subsequently formed. We propose that increased deamination lowers mitochondrial concentrations of glutamate and increases deamidation. In contrast, slowing deamination increases mitochondrial concentrations of glutamate and decreases deamidation.

Adenosine Diphosphate↗
PubMedDate not supplied

[Mechanism of disturbances in the deamination of nitrogenous compounds in experimental hypercholesterolemia and atherosclerosis].

Experimental alimentary hypercholesterolaemia in rabbits caused not only a decrease in deamination of monoamines (serotonin, benzylamine, tyramine) in liver, brain, kidney and heart mitochondrial fractions but also an appearance in these fractions of a qualitatively new reactions, namely that of cadaverine deamination, which was occasionally accompanied by stimulation of AMP deamination. In mitochondrial fractions from liver tissue obtained by autopsy in cases of ischemic heart disease accompanied by atherosclerosis, as compared with the corresponding fractions from the liver of persons who died in accidents and in whom no distinct morphological manifestations of atherosclerosis could be noted, there was observed a decrease in deamination of serotonin or tyramine (by 52% and 63%), appearance of cadaverine deamination (Vmax constitutes 35% of the Vmax value for serotonin deamination in the same fraction (and stimulation) 2-fold) of AMP deamination. The impairments in deamination of the nitrogenous compounds in experimental hypercholesterolaemia and in atherosclerosis are apparently due to qualitative alteration (transformation) in catalytic properties of mitochondrial monoamine oxidases. Implications of this hypothesis for future research on treatment of atherosclerosis are discussed.

Aged↗
PubMed1986

The effect of partial inhibition of monoamine oxidase on the steady-state rate of deamination of 3H-catecholamines in two metabolizing systems.

Two different "deaminating systems" were compared (i.e., intact tissues in which an uptake process translocates the 3H-catecholamine from the extracellular space to the intracellular MAO): the adrenergic nerve endings of the rat vas deferens exposed to 10 nmol/l 3H-(-)-noradrenaline, and the extraneuronal deaminating system of the rat heart perfused with 50 nmol/l 3H-(-)-adrenaline. Vesicular uptake and COMT were inhibited. In both systems MAO was partially inhibited by pargyline, and the steady-state tissue content of the 3H-catecholamine was determined as well as the steady-state rate of deamination. Rat vas deferens (preincubated with 10-40 nmol/l pargyline for 30 min). Inhibition of neuronal MAO caused not more than a moderate decrease of the steady-state rate of deamination of 3H-(-)-noradrenaline, but the steady-state tissue content was greatly increased. Determinations of the activity of MAO in homogenates of vasa deferentia showed that preincubation with 10 and 20 nmol/l pargyline inhibited the enzyme by 80 to 95%. Rat heart (of animals pretreated with 1 to 30 mg/kg pargyline). Inhibition of extraneuronal MAO caused a steep decline of the steady-state rate of deamination of 3H-(-)-adrenaline, but only a small rise in the steady-state tissue content. The decisive difference between the two deaminating systems lies in the fact that the ratio "kmao/kout" (where the two k-values characterize the activity of the unsaturated intracellular MAO and the ability of the 3H-catecholamine to leave the relevant cells, respectively) is much higher for the neuronal deaminating system exposed to 3H-(-)-noradrenaline than for the extraneuronal deaminating system exposed to 3H-(-)-adrenaline.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

The role of lipid peroxidation in the possible involvement of membrane-bound monoamine oxidases in gamma-aminobutyric acid and glucosamine deamination in rat brain. Focus on chemical pathogenesis of experimental audiogenic epilepsy.

Incubation of rat brain synaptosomes and mitochondria with LPO inducers (Fe2+ and ascorbate) was accompanied by a decrease of deamination of serotonin (substrate of MAO-A) in mitochondria, but not in synaptosomes, with simultaneous stimulation of GABA and GLCA deamination, apparently owing to modification of catalytic properties of brain membrane-bound MAO. Oxidation of PEA (substrate of MAO-B) was insignificantly altered in both fractions. Reactions of deamination of serotonin, GABA, and GLCA (but not PEA), were highly sensitive to a selective inhibitor of MAO-A pyrazidol (pyrlindole). Isoniazid and hydrazides of quinoline carbonic acids (inhibitors of both modified MAO and copper-containing amine oxidases) strongly inhibited deamination of GABA and GLCA. During epileptiformic seizures in rats, genetically selected for high incidence of audiogenic epilepsia, stimulation in brain synaptosomes and mitochondria of LPO was observed. This was accompanied by a marked decrease in serotonin and PEA deamination, with a simultaneous increase in GABA and GLCA deamination in both fractions. The data obtained suggest that appearance of GABA-deaminating activity owing to modification of catalytic properties of MAO, might be an essential pathogenetic component in the development of epileptic seizures.

Acoustic Stimulation↗
PubMed1993

A mechanism of inhibition of short-wavelength ultraviolet light-induced deamination of pyrimidine bases by ascorbic acid.

The relation of ascorbic acid to the ultraviolet light-induced deamination of cytosine (to uracil) and 5-methylcytosine (to thymine) was examined using gas chromatography-mass spectrometry. There was an inverse relation between the uracil content measured in solutions of cytosine after exposure to short wavelength (254 nm) ultraviolet light and the ascorbic acid concentration of the solution indicating inhibition of deamination of cytosine by ascorbic acid. Ascorbic acid also inhibited ultraviolet light-induced deamination of 5-methylcytosine. The ascorbic acid was only partially consumed during the exposure suggesting that protection from deamination was not due entirely to the antioxidant properties of ascorbic acid. Mercaptoethanol did not prevent ultraviolet light-induced deamination of either cytosine or 5-methylcytosine. However, near identical protection from ultraviolet light-induced deamination was provided by 4-aminobenzoic acid and ascorbic acid at equivalent ultraviolet light absorbing concentrations. This observation suggests that ascorbic acid prevents short wavelength ultraviolet light-induced deamination through absorbance of ultraviolet light rather than through antioxidant mechanisms.

5-Methylcytosine↗
PubMed1995

Deamination of cytosine-containing pyrimidine photodimers in UV-irradiated DNA. Significance for UV light mutagenesis.

The realization that cytosine in cyclobutyl pyrimidine dimers rapidly deaminates to uracil raised the possibility that this chemical transformation, rather than an enzymatic polymerase error, is the major mutagenic step in UV mutagenesis. We have established a sensitive bioassay system that enabled us to determine the rate of deamination of cytosine in cyclobutyl pyrimidine dimers in plasmid DNA. This was done by in vitro UV irradiation and deamination of a plasmid carrying the cro gene, followed by photoreactivation, and assaying uracils in DNA by their ability to cause Cro- mutations in an indicator strain that was deficient in uracil DNA N-glycosylase. DNA sequence analysis revealed that 27 out of 29 Cro- mutants carried GC --> AT transitions, as expected from deamination of cytosine. Deamination of cytosines in the cro gene in UV-irradiated plasmid pOC2 proceeded at 37 degrees C with first-order kinetics, at a rate of (3.9 +/- 0.6) x 10(-5) s-1, corresponding to a half-life of 5 h. Physiological salt conditions increased the half-life to 12 h, whereas decreasing the pH increased deamination. The temperature dependence of the rate constant yielded an activation energy of 13.6 +/- 3.3 kcal/mol. These kinetics data suggest that deamination of cytosine-containing dimers is too slow to play an important role in UV mutagenesis in Escherichia coli. However, it is likely to play an important role in mammalian cells, where the mutagenic process is slower.

Base Composition↗
PubMed1992

Predominance of oxidative deamination in the metabolism of exogenous noradrenaline by the normal and chemically denervated human uterine artery.

Longitudinal strips were prepared from human uterine arteries obtained at hysterectomy. The artery had a low content of noradrenaline and dopamine, contrasting with a high content of the deaminated catechols, dihydroxyphenylglycol (DOPEG) and dihydroxymandelic acid (DOMA), which together represented 98% of endogenous catechols. When incubated with 3H-noradrenaline (0.1 mumol/l), the uterine artery removed, accumulated and metabolized noradrenaline. Deaminated metabolites predominated, DOMA being the most abundant metabolite. Cocaine markedly reduced the accumulation of 3H-noradrenaline and abolished 3H-DOPEG formation, but did not change 3H-DOMA. Selective monoamine oxidase (MAO) inhibitors (clorgyline, selegiline and 2-amino ethyl carboxamide derivatives) caused a marked decrease in the amounts of 3H-DOPEG, 3H-DOMA and 3H-O-methylated and deaminated metabolites (OMDA) formed by the tissue and an increase in 3H-normetanephrine (NMN) formation. Inhibition of catechol-O-methyltransferase suppressed NMN formation and reduced that of OMDA; hydrocortisone slightly depressed the formation of DOMA and OMDA. Homogenates of the uterine artery deaminated 3H-5-HT, 14C-phenylethylamine and 3H-tyramine; inhibition curves of the deamination of 3H-tyramine by clorgyline and selegiline were compatible with the presence of both MOA A and MOA B. Exposure of the strips to 6-hydroxydopamine (1.5 mmol/l for 20 min; 3 exposure periods followed by washout periods of 15,15 and 30 min) resulted in complete and selective chemical denervation of the arterial tissue. This chemical denervation had effects which were similar to those of cocaine. The 2-amino ethyl carboxyamide derivatives markedly reduced the formation of deaminated metabolites by the denervated strips.(ABSTRACT TRUNCATED AT 250 WORDS)

Arteries↗
PubMed1989

Kinetic deuterium isotope effects on deamination and N-hydroxylation of cyclohexylamine by rabbit liver microsomes.

Deuterium isotope effects on the kinetic parameters for deamination and N-hydroxylation of cyclohexylamine (CHA) catalyzed by rabbit liver microsomes with NADPH are investigated. Both reactions are inhibited by carbon monoxide and have the characteristics of typical cytochrome P450-dependent monooxygenase reactions. A small and significant deuterium isotope effect operates in the oxidative deamination of CHA. The apparent isotope effects, i.e., VH/VD and (V/K)H/(V/K)D ratios for deamination, are 1.75 and 1.8-2.3, respectively. On the basis of N-hydroxylation, the VH/VD and (V/K)H/(V/K)D ratios are 0.8-0.9. The N-hydroxylation rate of alpha-deuterated CHA (D-CHA) is somewhat higher than that of CHA. The increased increment of hydroxylamine formation seems to coincide with the decreased amount of deamination. Substitution of deuterium in the alpha-position of CHA results in metabolic switching of cytochrome P450 from deamination to N-hydroxylation with low deuterium isotope effects. The data are interpreted in terms of an initial one-electron abstraction from the nitrogen to form an aminium cation radical followed by recombination with iron-bound hydroxyl radical leading to N-hydroxylamine, or followed by alpha-carbon deprotonation to form a neutral carbon radical. The latter can lead to a carbinolamine intermediate for deamination by way of imine or recombination with nascent iron-bound hydroxyl radical. The relative rates of the reactions depend on the alpha-carbon deprotonation rates of amines.

Animals↗