Deaminations oxidative

The carbinol, by another reaction sequence, can also give rise to an oxime  

The oxime can now be hydrolyzed to yield the ketone, which is thus formed by two different routes  

Braunstein and Azarkh (27,28) demonstrated that certain 2-amino acids are actually deaminated in this manner in surviving kidney tissue. 

When ground and diluted with saline solutions, pig or rat kidney tissue fails to de-aminate 1-amino acids. In the homogenised suspensions, deamination of QL is restored by the addition of oosymase. When supplemented with cozymase and KG, the homogenates deaminate AS, AL, 2-cysteic acid, valine, -leucine and -isoleuoine at rates comparable to their rates of deamination in intact kidney slices deamination in the homogenate is negligible if either eozymase or KG is omitted. 

The deamination rates of the amino acids mentioned in supplemented homogmiatei 

GL AS AL Cysteic acid Valine Leucine Isoleucine All other amino acids ( -serine, -methionine and -phenylalanine were not accessible) were inactive in either of the reactions (a), (b) and (o). 

Deaminatum of -Amino Acids in Homogenued Pig Kidney Cortex (Braunstein and Azarkh, 27.) 

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Strecker Degradation (Oxidative Deamination), Mild oxidizing agents such as aqueous sodium hypochlorite or aqueous A-bromosuccinimide, cause decarboxylation and concurrent deamination of amino acids to give aldehydes. 

Monoamine Oxidase Inhibitors. MAOIs inactivate the enzyme MAO, which is responsible for the oxidative deamination of a variety of endogenous and exogenous substances. Among the endogenous substances are the neurotransmitters, norepinephrine, dopamine, and serotonin. The prototype MAOI is iproniazid [54-92-2] (25), originally tested as an antitubercular dmg and a close chemical relative of the effective antitubercular, isoniazid [54-85-3] (26). Tubercular patients exhibited mood elevation, although no reHef of their tuberculosis, following chronic administration of iproniazid. In... 

Two important pathways for catecholamine metaboHsm are 0-methylation by COMT, which is cytoplasmicaHy localized, and oxidative deamination by the mitochondrial localized enzyme MAO. There are large amounts of MAO in tissues such as the fiver and the heart which are responsible for the removal of most of the circulating monoamine, including some taken in from the diet. Tyramine is found in high concentrations in certain foods such as cheese, and in wine. Normally, this tyramine is deaminated in the fiver. However, if MAO is inhibited, the tyramine may then be converted into octopamine [104-14-37] which may indirecdy cause release of NE from nerve terminals to cause hypertensive crisis. Thus MAO, which is relatively nonspecific, plays an important role in the detoxification of pharmacologically active amines ingested from the diet. 

Ubiquitous mitochondrial monoamine oxidase [monoamine oxygen oxidoreductase (deaminating) (flavin-containing) EC 1.4.3.4 MAO] exists in two forms, namely type A and type B [ monoamine oxidase (MAO) A and B]. They are responsible for oxidative deamination of primary, secondary, and tertiary amines, including neurotransmitters, adrenaline, noradrenaline, dopamine (DA), and serotonin and vasoactive amines, such as tyramine and phenylethylamine. Their nonselec-tive and selective inhibitors ( selective MAO-A and -B inhibitors) are employed for the treatment of depressive illness and Parkinson s disease (PD). 

Urea biosynthesis occurs in four stages (1) transamination, (2) oxidative deamination of glutamate, (3) ammonia transport, and (4) reactions of the urea cycle (Figure 29-2). 

Figure 29-6. Oxidative deamination catalyzed by L-amino acid oxidase (i-a-amino acidiOj oxidoreduc-tase). The a-imino acid, shown in brackets, is not a stable intermediate.

Oxidative deamination ofe-amino groups of lysyl and hydroxylysyl residues to aldehydes... 

After secretion from the cell, certain lysyl residues of tropoelastin are oxidatively deaminated to aldehydes by lysyl oxidase, the same enzyme involved in this process in collagen. However, the major cross-links formed in elastin are the desmosines, which result from the condensation of three of these lysine-derived aldehydes with an unmodified lysine to form a tetrafunctional cross-hnk unique to elastin. Once cross-linked in its mature, extracellular form, elastin is highly insoluble and extremely stable and has a very low turnover rate. Elastin exhibits a variety of random coil conformations that permit the protein to stretch and subsequently recoil during the performance of its physiologic functions. 

MAO is bound to the outer membrane of mitochondria and is responsible for the oxidative deamination of noradrenaline. There are two isoforms of this enzyme, MAO-A... 

Figure 8.8 The metabolic pathway(s) for noradrenaline. MAO is responsible for the oxidative deamination of noradrenaline derivatives while COMT 0-methylates noradrenaline. Most intraneuronal metabolism involves MAO while COMT is mainly found extraneuronally. However, both these enz5unes can act on each other s products, yielding a complex cocktail of metabolites. The reasons for this complex network of metabolites are not known...

As an alternative to oxidative deamination, decarboxylation is involved in polyamine biosynthesis and in the protection of enteric bacteria from acidic conditions. Under these conditions, the electrons used to form the ketimine are provided by decarboxylation in place of those from the a-methine group. 

The gene tdnQ that encodes the oxidative deamination of aniline is carried on a plasmid in strains of Comamomas testosteroni and Delftia acidovorans. However, it has not been resolved whether this enzyme is involved in the degradation of 3-chloroaniline, because the gene is transcribed in the presence of aniline, but not when only 3-chloroaniline is present (Boon et al. 2001). 

The beneficial effect of deprenyl in Parkinson s disease was su ested to be in part due to its effect on increasing the levels of SOD activity in several brain regions (Carrillo et al., 1993). Deprenyl is known to inhibit monoamine oxidase type B, which results in a reduction in hydrogen peroxide formation by blockade of the oxidative deamination of dopamine. That is believed to be the major mechanism of action of this drug in inhibiting the progression of Parkinson s disease. 

Hydrogen peroxide is present in normal aqueous (approximately 30 /imol/1) whilst mean concentrations of around 70 tmol/l have been reported in aqueous from patients with cataracts, supporting a role for oxidative damage in the formation of cataracts (Spector and Garner, 1981). Diamine oxidase is one of the few enzymes to have been detected in bovine aqueous humour (albeit in trace quantities). It has been su ested that the hydrogen peroxide present in aqueous may be the product of the oxidative deamination of diamine substrates. This hypothesis is still unproven, since diamine oxidase substrates have not been identified in aqueous humour. 

Several lupin alkaloids have been derived from the unsaturated quinalozidine 433, that was obtained in the treatment of amine 431 with ortho-quinone 432. This quinone behaves as a model of topaquinone, the cofactor of copper-containing amine oxidases. The cyclization step involved a nucleophilic attack of the piperidine nitrogen of 431 onto a side-chain aldehyde function that is unmasked by the oxidative deamination. Quinolizine 433, when treated with dehydropiperidine, gave the oxime ether 434 that, on ozonolysis followed by reduction, afforded sparteine 10, presumably via the bis(iminium) system 435 (Scheme 102) <1996JOC5581>. 

Clark et al. [136] studied the excretion, distribution, and metabolism of primaquine in rats. The drug was administered intravenously, intraperitoneally, and orally and blood samples were collected at various time intervals. Primaquine was metabolized by oxidative deamination to give 8-(3-carboxy-l-methylpropylamino)-6-methoxy quinoline. The plasma levels of both primaquine and its metabolites were determined by high performance liquid chromatography. 

Ni et al. [143] investigated the profile of the major metabolites of primaquine produced by in vitro liver microsomal metabolism, with silica gel thin-layer and high performance liquid chromatography analysis. Results indicated that the liver microsomal metabolism could simultaneously produce both 5-hydroxyprimaquine (quinoline ring oxidation product) and carboxyprimaquine (side-chain oxidative deamination product). However, the quantitative comparative study of microsomal metabolism showed that the production of 5-hydroxyprimaquine was far much higher than that of carboxyprimaquine. 

Not all mutagenesis in IS. coli is dependent on SOS-processing. Mutations may arise quite simply during DNA replication if a base is substituted by or converted to another, incorrect, base. Consider the consequence of oxidative deamination of the base 5-methylcytosine to thymine. Replication followed by daughter strand segregation will result in a G C base pair having been mutated to an A T base pair. Sites containing 5-methylcytosine are hotspots for G C to A T transitions in 12. coli (24). 

The primary catabolic pathway for 5-HT is oxidative deamination by the enzyme monoamine oxidase 237 In addition to classical synaptic transmission, 5-HT may relay information by volume transmission or paracrine neurotransmission 238 5 -HT may be involved in a wide variety of behaviors by setting the tone of brain activity in relationship to the state of behavioral arousal/activity 238... 

The major biotransformations of pseudoephedrine hydrochloride are parahydroxylation, N-demethylation, and oxidative deamination.14 The proposed pathways for the metabolism of pseudoephedrine are shown in Figure 6. 

Taken together, the data presented here show that many phenyl- and in-dolealkylamines are hallucinogenic in man and behaviorally active in animals. In both series, primary amines penetrate the blood-brain barrier with difficulty, although this seems to be more of a problem with tryptamines (and even N-monoalkyltryptamines) than with phenethylamines. This situation is somewhat alleviated in the presence of an alpha-methyl substituent. The primary amines are also prone to rapid metabolism by oxidative deamination. Metabolism, however, can be impeded by the presence of an alpha-methyl or N-alkyl function. 

Tryptamines that are unsubstituted on the terminal amine are good substrates for oxidative deamination by MAO. Furthermore, it has been demonstrated that tryptamine and 5-methoxytryptamine cross the blood-brain barrier with great difficulty administration of 50 mg/kg 5-methoxytryptamine to rats results in a low brain/plasma ratio when measured 15 min postadministration (242). 

Aryl and alkyl hydroxylations, epoxide formation, oxidative dealkylation of heteroatoms, reduction, dehalogenation, desulfuration, deamination, aryl N-oxygenation, oxidation of sulfur Oxidation of nucleophilic nitrogen and sulfur, oxidative desulfurization Oxidation of aromatic hydrocarbons, phenols, amines, and sulfides oxidative dealkylation, reduction of N-oxides Alcohol oxidation reduction of ketones Oxidative deamination... 

While the cytochrome P-450 monooxygenase reaction described in Eq. (1) often involves hydroxylation of carbon, many other reactions are catalyzed by these enzyme systems. These reactions include oxidation of nitrogen and sulfur, epoxidation, dehalogenation, oxidative deamination and desulfuration, oxidative N-, O-, and S-dealkylation, and peroxidative reactions (56). Under anaerobic conditions, the enzyme system will also catalyze reduction of azo, nitro, N-oxide, and epoxide functional groups, and these reductive reactions have been recently reviewed (56, 57). Furthermore, the NADPH-cytochrome P-450 reductase is capable of catalyzing reduction of quinones, quinonimines, nitro-aromatics, azoaromatics, bipyridyliums, and tetrazoliums (58). 

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