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PubMedDate not supplied

[Biogenic amine deamination in experimental tuberculosis].

Stimulation of lipid peroxidation /increase in content of conjugated dienes and of malone dialdehyde/, which was prevented by administration of isoniazid or sodium thiosulphate, was detected in mitochondrial fraction of liver tissue obtained from rats with tuberculosis of lungs. At the same time, in the mitochondrial fraction a significant decrease in tyramine and serotonin deamination rates and an increase in histamine, lysine and putrescine deamination rates were observed. The altered ratio of the deamination rates of the nitrogenous compounds may be prevented by administration of isoniazid and sodium thiosulphate into the animals. A hypothesis is discussed on the possible significance of qualitative alteration /transformation/ in catalytic properties of the mitochondrial monoamine oxidase induced by the stimulation of lipid peroxidation as a cause underlying the reversible impairments in ratios of rates of the nitrogenous compounds deamination in tuberculosis.

Ammonia↗
PubMed1984

[Disorders of the deamination of nitrogenous compounds in the heart muscle in experimental atherosclerosis].

The development of alimentary hypercholesterolemia in rabbits (confirmed by morphometric, electrophysiological and biochemical data) was accompanied by a decrease of the serotonin, benzylamine and tyramine deamination rates in heart muscle mitochondria. At the same time a qualitatively new reaction of cadaverine deamination could be seen in the mitochondria. The data obtained suggest that impairment of deamination of the nitrogenous compounds in atherosclerosis may be due to reversible qualitative modification (transformation) of mitochondrial monoamine oxidase activity. Some of the drugs which decrease the level of lipids in blood serum of hypercholesterolemic rabbits abolished and prevented the impairment of deamination of nitrogenous compounds.

Animals↗
PubMed1984

[Conjugated dinitrocompound dianions as inhibitors of the oxidative deamination of monoamines].

The conjugated derivatives--1.4-dinitrobutene-2, 1,4-dinitro-2-methylbutene-2, 1,4-dinitro-2,3-diphenylbutene-2 sodium salts, as well as dinitromethane sodium salt and beta-nitrostyrol, the inhibitors of oxidative deamination of serotonin, tyramine, tryptamine and benzylamine in bovine liver mitochondria, were studied. All the derivatives under study were found to be active inhibitors of monoamine oxidase catalyzing the oxidative deamination of serotonin, tyramine and tryptamine. In a far lesser degree these preparations inhibited the deamination of benzylamine, a specific substrate for monoamine oxidase B. All the dinitrocompound dianions, with the exception of 1,4-dinitro-2,3-diphenylbutene-2 disodium salt, a non-competitive inhibitor of oxidative deamination of the four substrates under study, cause competitive reversible inhibition of monoamine oxidase.

Alkenes↗
PubMed1983

Differential properties of the microsomal deamination and hydroxylation reactions.

The addition of 1 mM of the metal complexing reagents such as EDTA, alpha, alpha'-dipyridyl, 1,10-phenanthroline and Tiron to the incubation of benzylamine, aminopyrine, p-nitroanisole and aniline, respectively, inhibited selectively the microsomal deamination of benzylamine, whereas the addition of the monoamine oxidase inhibitors tranylcypromine, nialamide and iproniazid specifically decreased the metabolism of aminopyrine, p-nitroanisole and aniline. Pretreatment of rats with 3,4-benzpyrene or phenobarbital increased the liver microsomal concentration of cytochrome P-450 (448) and the rate of aminopyrine and p-nitroanisole demethylation and of aniline hydroxylation whereas pretreatment cytochrome P-450 depressor agents such as cadmium or cobalt lowered the concentration of the hemoprotein and decreased the rate of the demethylation reactions. Phenobarbital and 3,4-benzpyrene pretreatment had either no effect or decreased significantly the rate of the microsomal deamination reaction respectively. The administration of cadmium slightly decreased the rate of benzylamine deamination whilst cobalt produced no significant effect. These results indicate that the microsomal oxidative deamination reaction has different properties than the dealkylation and aromatic hydroxylation reactions, thus suggesting a different enzyme system.

Aminopyrine↗
PubMedDate not supplied

[Deamination reactions involving several nitrogen compounds and mammalian radioresistance].

Inhibition of monoamine oxidase (substrates tyramine or serotonin) with simultaneous appearance of diamine oxidase (substrates histamine or putrescine) and distinct increase in AMP-deaminating activities were found after total body X-ray irradiation (700 r) of white mice or rats in mitochondrial fractions isolated from their liver and intestines. These impairments in deamination of nitrogenous compounds in liver mitochondria of guinea pigs, which are must less radioresistant as compared with mice or rats, were noted after the irradiation at a dose 300 r, but in the liver mitochondria of mongolian gerbyls (Mariones unguiculatus), which are highly radioresistant, the irradiation even at a dose 1500 r did not cause appearance either of histamine or of AMP-deaminating activities while the decrease in the monoamine oxidase activity was not statistically significant. Feeding to the mice the grasses, which comprize the fodder of mongolian gerbyls under natural conditions, increased radioresistance of the animals and prevented at the same time appearance in the mitochondrial fractions of liver and intestines of those impairments in deamination of nitrogenous compounds which accompanied development of irradiation injuries.

Adenosine Monophosphate↗
PubMed1988

The handling of five amines by the extraneuronal deaminating system of the rat heart.

The handling of five amines by the extraneuronal deaminating system was studied in perfused hearts of rats (pretreated with reserpine; COMT and neuronal uptake inhibited). Hearts were perfused with 50 nmol/l 3H-noradrenaline for 30 min, in the presence of increasing concentrations of unlabelled (-)-adrenaline, (-)-noradrenaline, dopamine, tyramine and 5-HT. IC50's were determined as those concentrations of unlabelled amines which halved the steady-state rate of deamination of 3H-noradrenaline. After correction for changes in the tissue/medium ratio for 3H-noradrenaline, "half-saturating outside concentrations" were obtained. They increased in the order (-)-adrenaline (15 mumol/l) - tyramine - dopamine - noradrenaline - 5-HT (53 mumol/l). The Vmax for extraneuronal deamination was determined for 3H-(-)-adrenaline, 3H-(-)-noradrenaline and 3H-dopamine, as well as (by HPLC and electrochemical detection) for tyramine and 5-HT. It was low for (-)-adrenaline, intermediate for (-)-noradrenaline, dopamine and 5-HT, high for tyramine. For the three catecholamines the half-saturating outside concentrations of the extraneuronal deaminating system clearly exceeded those for the extraneuronal O-methylating system of the same organ (see Grohmann and Trendelenburg 1985), although the two enzymes appear to co-exist in the same cells, so that the same transport system is involved.

Animals↗
PubMed2006

Potential artifacts in the measurement of DNA deamination.

Attack on DNA by some reactive nitrogen species results in deamination of adenine and guanine, leading to the formation of hypoxanthine and xanthine, respectively. Published levels of these products in cellular DNA have varied widely. Although these two deamination products are often measured by GC-MS analysis, the procedure of acid hydrolysis to release DNA bases for derivatization poses a risk of artifactual deamination of the DNA. In this study, we demonstrated the artifactual formation of these two deamination products during acid hydrolysis and hence developed a method for detecting and measuring 2'-deoxyinosine, the nucleoside of hypoxanthine. Our assay for 2'-deoxyinosine employs nuclease P1 and alkaline phosphatase to achieve release of the nucleosides from DNA, followed by HPLC prepurification with subsequent GC-MS analysis of the nucleosides. This assay detected an increase in the levels of 2'-deoxyinosine in DNA when commercial salmon testis DNA was treated with nitrous acid. We also used it to measure levels in various rat tissues of both normal and endotoxin-treated rats, but could not find increased 2'-deoxyinosine formation in tissues even though *NO production was substantially increased.

Amination↗
PubMed1985

Human brain monoamine oxidase type B: mechanism of deamination as probed by steady-state methods.

Recently, evidence has been published which suggests that [Husain, M., Edmondson, D. E., & Singer, T.P. (1982) Biochemistry 21, 595-600] monoamine oxidase [amine:oxygen oxidoreductase (MAO), EC 1.4.3.4] deaminates phenylethylamine and benzylamine via two distinct kinetic pathways which involve either binary or ternary complex formation, respectively. These conclusions were drawn largely from stopped-flow kinetic analysis performed on purified enzyme removed from its native membrane and in the presence of the inhibitory detergent Triton X-100. In this study, d-amphetamine and alternative substrates were used as steady-state probes of the kinetics of deamination by the B form of human brain MAO using native membrane-bound enzyme. Initial velocity studies showed mixed-type patterns for amphetamine inhibition of phenylethylamine, tryptamine, and tyramine when either amine or oxygen was the varied substrate. Slope and intercept vs. amphetamine concentration replots were linear in all cases except for phenylethylamine (hyperbolic); Ki values obtained from linear replots of slope or intercept values were comparable. In contrast, amphetamine was a competitive inhibitor of benzylamine deamination when amine concentration was varied and uncompetitive when oxygen concentration was varied; slope and intercept replots were linear for both. When benzylamine was the alternative substrate inhibitor and tyramine and tryptamine deamination was measured, mixed-type inhibition patterns were obtained when either amine or oxygen concentration was varied; replots of slope and intercept were linear in all cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain↗
PubMed1999

The thymine glycosylase MBD4 can bind to the product of deamination at methylated CpG sites.

In addition to its well-documented effects on gene silencing, cytosine methylation is a prominent cause of mutations. In humans, the mutation rate from 5-methylcytosine (m5C) to thymine (T) is 10-50-fold higher than other transitions and the methylated sequence CpG is consequently under-represented. Over one-third of germline point mutations associated with human genetic disease and many somatic mutations leading to cancer involve loss of CpG. The primary cause of mutability appears to be hydrolytic deamination. Cytosine deamination produces mismatched uracil (U), which can be removed by uracil glycosylase, whereas m5C deamination generates a G x T mispair that cannot be processed by this enzyme. Correction of m5CpG x TpG mismatches may instead be initiated by the thymine DNA glycosylase, TDG. Here we show that MBD4, an unrelated mammalian protein that contains a methyl-CpG binding domain, can also efficiently remove thymine or uracil from a mismatches CpG site in vitro. Furthermore, the methyl-CpG binding domain of MBD4 binds preferentially to m5CpG x TpG mismatches-the primary product of deamination at methyl-CpG. The combined specificities of binding and catalysis indicate that this enzyme may function to minimize mutation at methyl-CpG.

Amino Acid Sequence↗
PubMed2003

Transcription-targeted DNA deamination by the AID antibody diversification enzyme.

Activation-induced cytidine deaminase (AID), which is specific to B lymphocytes, is required for class switch recombination (CSR)--a process mediating isotype switching of immunoglobulin--and somatic hypermutation--the introduction of many point mutations into the immunoglobulin variable region genes. It has been suggested that AID may function as an RNA-editing enzyme or as a cytidine deaminase on DNA. However, the precise enzymatic activity of AID has not been assessed in previous studies. Similarly, although transcription of the target immunoglobulin locus sequences is required for both CSR and somatic hypermutation, the precise role of transcription has remained speculative. Here we use two different assays to demonstrate that AID can deaminate specifically cytidines on single-stranded (ss)DNA but not double-stranded (ds)DNA substrates in vitro. However, dsDNA can be deaminated by AID in vitro when the reaction is coupled to transcription. Moreover, a synthetic dsDNA sequence, which targets CSR in vivo in a manner dependent on transcriptional orientation, was deaminated by AID in vitro with the same transcriptional-orientation-dependence as observed for endogenous CSR. We conclude that transcription targets the DNA deamination activity of AID to dsDNA by generating secondary structures that provide ssDNA substrates.

Amination↗
PubMed1990

The specific binding of nuclear protein(s) to the cAMP responsive element (CRE) sequence (TGACGTCA) is reduced by the misincorporation of U and increased by the deamination of C.

Point mutations in the cAMP-responsive element (CRE) of the rat somatostatin gene promoter/enhancer sequence (TGACGTCA) were used as a model for assessing the effect of uracil, deriving either from misincorporation during DNA synthesis (T----U) or cytosine deamination (C----U), on the binding of sequence/specific regulatory proteins. The results show that the T----U conversion in both strands of the CRE palindromic sequence reduces its affinity for the CRE binding factor(s), suggesting the crucial role of the methyl group contributed by T for the correct recognition of the sequence. On the other hand, deamination of C in the CpG central dinucleotide (CpG----UpG) causes an increase of binding affinity which is further enhanced by the contemporary deamination in both strands. Then, both uracil misincorporation and cytosine deamination alter the binding to CRE sequence in vitro, suggesting that uracil, if not removed by uracil DNA-glycosylase, could be dangerous for cellular functions.

Animals↗
PubMed1988

Three types of stereospecificity and the kinetic deuterium isotope effect in the oxidative deamination of dopamine as catalyzed by different amine oxidases.

When the stereospecifically deuterated dopamine enantiomers, (R)- and (S)-[alpha-2H1]dopamine, are incubated with amine oxidases, the deuterium atom may be either retained to form monodeuterated 3,4-dihydroxyphenylacetaldehyde, or eliminated to produce the nondeuterated or protio-aldehyde product. These two aldehydes can be separated from one another and identified by high-performance liquid chromatography with electrochemical detection. Three types of stereospecific abstraction of a hydrogen from the alpha-carbon of dopamine during deamination have been observed. In the first type, the pro-R hydrogen is removed from the alpha-carbon. Enzymes in this category are mitochondrial monoamine oxidases A and B, as isolated from different tissues and species. The second type of deamination involves the abstraction of pro-S hydrogen from the alpha-carbon of dopamine. Soluble enzymes, such as rat aorta benzylamine oxidase or diamine oxidase from hog kidney and pea seedling, have been found to belong to this group. Bovine plasma amine oxidase exhibits the third type of deamination where no absolute stereospecificity is required. This enzyme catalyzes the oxidation of either (S)- or (R)-[alpha-2H1]dopamine, preferably breaking the C-H bond rather than the C-2H bond in both cases. The kinetic deuterium isotope effect during the deamination of dopamine catalyzed by the different amine oxidases varies greatly; VH/VD ranges from 1.5 to 5.5. The high magnitude of the isotope effect suggests that hydrogen abstraction may be the rate-limiting step (i.e., in reactions catalyzed by benzylamine oxidase and monoamine oxidase). When the isotope effect is low (i.e., for diamine oxidases from hog kidney or pea seedling), it is uncertain if the breaking of the bond is rate limiting.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1975

Oxidative deamination of biogenic amines by intestinal amine oxidases: histamine is specifically inactivated by diamine oxidase.

The ability of the gut to inactivate various amines by oxidative deamination was tested with a 130-fold purified amine oxidase preparation from dog small intestine. Of 34 amines tested, putrescine, benzylamine, cadaverine, and serotonin were the most favourable substrates. Histamine was inactivated rapidly by this enzyme preparation, too. Histamine derivatives methylated at the imidazole nucleus were also deaminated, whereas Nalpha-methylhistamine was only a poor substrate and Nalpha, Nalpha-dimethylhistamine was not a substrate at all. Using a second procedure for the purification of amine oxidases from gut, the separation of a soluble monoamine oxidase from diamine oxidase was achieved by gel filtration on Sephadex G-200. The diamine oxidase deaminated putrescine (Km = 1.3 x 10(-4)M) and histamine (Km = 6.6 x 10(-5)M), but not serotonin, and was inhibited by aminoguanidine, but not by pargyline. The soluble monoamine oxidase inactivated serotonin (Km = 4.5 x 10(-4)M), but not histamine and putrescine and was inhibited by pargyline, but not by aminoguanidine. It was concluded that in dog small intestine (as well as in rabbit small intestine) only diamine oxidase was capable of inactivating histamine by oxidative deamination.

Amine Oxidase (Copper-Containing)↗
PubMed2004

Advantages and disadvantages of cytidine deamination.

Cytidine deamination of nucleic acids underlies diversification of Ig genes and inhibition of retroviral infection, and thus, it would appear to be vital to host defense. The host defense properties of cytidine deamination require two distinct but homologous cytidine deaminases-activation-induced cytidine deaminase and apolipoprotein B-editing cytidine deaminase, subunit 3G. Although cytidine deamination has clear benefits, it might well have biological costs. Uncontrolled cytidine deamination might generate misfolded polypeptides, dominant-negative proteins, or mutations in tumor suppressor genes, and thus contribute to tumor formation. How cytidine deaminases target a given nucleic acid substrate at specific sequences is not understood, and what protects cells from uncontrolled mutagenesis is not known. In this paper, I shall review the functions and regulation of activation-induced cytidine deaminase and apolipoprotein B-editing cytidine deaminase, subunit 3G, and speculate about the basis for site specificity vis-à-vis generalized mutagenesis.

APOBEC-1 Deaminase↗
PubMedDate not supplied

[Normalization of impairments in deamination of nitrogen compounds in experimental hypercholesterolemia].

Appearance of cadaverine deaminating activity in mitochondrial fractions of liver and kidney of rabbits with experimental alimentary hypercholesterolaemia was prevented by an antioxant diludin (2,6-dimethyl-3,5-diethoxycarbonyl-1,4-dihydropyridine) which also decreased the abnormally elevated AMP-deaminating activity and elevated the decreased monoamine oxidase activity (substrates: serotonin, benzylamine, tyramine). In heart and brain tissues as compared with liver and kidney the impairments caused by hypercholesterolaemia and the normalizing effect of diludin were less distinct. The effects of diludin could be reproduced by nucleophylic reagents sodium thiosulphate or ascorbate. The normalization of impairments in deamination of nitrogenous compounds in hypercholesterolaemia was accompanied by improvement in morpho-physiological manifestations of atherosclerosis (injury of aortal intima, alteration in heart rhythm, changes in content of cholesterol, triglycerides and lipoproteins in blood serum). The data obtained are in agreement with the hypothesis on the significance of qualitative alteration (transformation) in catalytic properties of mitochondrial monoamine oxidases in the mechanism of impairments in deamination of nitrogenous compounds in atherosclerosis.

AMP Deaminase↗
PubMed1999

Assessment of the deamination of aminoacetone, an endogenous substrate for semicarbazide-sensitive amine oxidase.

Methylglyoxal, a toxic aldehyde, has been reported to be increased in diabetes and has been claimed to be related to diabetic complications. Aminoacetone, an intermediate in the metabolism of threonine and glycine, has been proposed to be an endogenous substrate for semicarbazide-sensitive amine oxidase (SSAO). Methylglyoxal is the product. An HPLC procedure for the determination of SSAO activity toward aminoacetone in vitro is described. It was observed in previous assays that methylglyoxal formed via deamination of aminoacetone was quite unstable and led to erroneous results. o-Phenylenediamine (o-PD) was therefore employed for derivatization of methylglyoxal. o-PD does not affect SSAO activity and can be included in the enzyme reaction mixture for continuous trapping of methylglyoxal. This can avoid the loss of methylglyoxal during incubation. Deamination of aminoacetone by human umbilical artery SSAO was confirmed with this improved assay. The values of Km and Vmax, are 125.9 +/- 20.5 microM and 332.2 +/- 11.7 nmol/h/mg protein, respectively. Deamination of aminoacetone was nearly completely inhibited by 1 mM semicarbazide and 1 microM MDL-72974A, a potent selective SSAO inhibitor, whereas MAO inhibitors clorgyline (1 mM) and deprenyl (1 mM) had no inhibitory effect.

Acetone↗
PubMed1994

Unusual kinetics of uracil formation in single and double-stranded DNA by deamination of cytosine in cyclobutane pyrimidine dimers.

Mutagenesis studies have indicated that the deamination of cytosine in UV-induced cyclobutane pyrimidine dimers is a key part of an error-free process that can account for most of the C-->T base specificity that frequently characterizes UV-induced mutagenesis. The kinetics of deamination, as inferred from the mutagenic effect of delayed photoreactivation, is remarkable in its resemblance to a step function. To study the kinetics from a different point of view, we used an enzymatic approach combining photolyase and uracil-N-glycosylase treatment to detect the formation of uracil in UV-irradiated single or double-stranded infectious DNA of phage S13. Formation of abasic sites by removal of uracil was inferred from loss of infectivity. It is concluded that no uracil appeared at 37 degrees C within 20 minutes (single-stranded DNA) or 40 minutes (double-stranded DNA) after irradiation, but following those latent periods, most of the uracil residues rapidly appeared within a brief 14 minute period centered at 29 minutes (single-stranded DNA) and 55 minutes (double-stranded DNA) after irradiation. The timing appears to fully confirm the previous evidence that dimer cytosines in DNA deaminate with step-function-like kinetics. Furthermore, the appearance of uracil was shown to be dependent on the UV-induction of cyclobutane dimers containing cytosine.

Apurinic Acid↗
PubMed1985

Effects of clorgyline and (-)deprenyl on the deamination of normetanephrine and noradrenaline in strips and homogenates of the canine saphenous vein.

The influence of specific inhibitors of MAO A (clorgyline) and MAO B [(-)deprenyl] on the metabolism of normetanephrine (NMN) in strips of canine saphenous vein was studied, both in the absence and in the presence of inhibitors of neuronal (cocaine) and extraneuronal (hydrocortisone) uptake. Moreover, the formation of metabolites of noradrenaline and of NMN by saphenous vein homogenates and the influence of clorgyline or (-)deprenyl on this formation are described. Clorgyline reduced to the same degree (by about 70%) the formation of methoxy-hydroxy-phenylglycol (MOPEG) and of vanillylmandelic acid (VMA) in strips incubated with NMN, whereas (-)deprenyl reduced by about 50% the formation of MOPEG and had no effect on VMA production. Hydrocortisone had effects very similar to those of (-)deprenyl. Saphenous vein homogenates (O-methylation inhibited), deaminated both noradrenaline and NMN; clorgyline and (-)deprenyl reduced the formation of metabolites of both noradrenaline and NMN. It is concluded that both MAO A and B are able to deaminate noradrenaline and NMN, but that in the intact tissue the former has no access to MAO B. Even in intact tissues MAO B may play a role in the metabolism (but not in the inactivation) of noradrenaline by deaminating the NMN formed from noradrenaline and giving preferentially origin to MOPEG.

Animals↗