Histidine deamination

Histamine is synthesised by decarboxylation of histidine, its amino-acid precursor, by the specific enzyme histidine decarboxylase, which like glutaminic acid decarboxylase requires pyridoxal phosphate as co-factor. Histidine is a poor substrate for the L-amino-acid decarboxylase responsible for DA and NA synthesis. The synthesis of histamine in the brain can be increased by the administration of histidine, so its decarboxylase is presumably not saturated normally, but it can be inhibited by a fluoromethylhistidine. No high-affinity neuronal uptake has been demonstrated for histamine although after initial metabolism by histamine A-methyl transferase to 3-methylhistamine, it is deaminated by intraneuronal MAOb to 3-methylimidazole acetic acid (Fig. 13.4). A Ca +-dependent KCl-induced release of histamine has been demonstrated by microdialysis in the rat hypothalamus (Russell et al. 1990) but its overflow in some areas, such as the striatum, is neither increased by KCl nor reduced by tetradotoxin and probably comes from mast cells. 

Some amino acids are converted to glutamate prior to deamination these are proline, arginine, histidine and glutamine (Figure 8.12). 

Eliminating deamination takes place in the degradation of histidine and serine. H2O is first eliminated here, yielding an unsaturated intermediate. In the case of serine, this intermediate is first rearranged into an imine (not shown), which is hydrolyzed in the second step into NH3 and pyruvate, with H2O being taken up. H2O does not therefore appear in the reaction equation. 

Flavin-containing mitochondrial MAO-A and MAO-B catalyze the oxidative deamination of neurotransmitters, such as dopamine, serotonin, and norepinephrine in the central nervous system and peripheral tissues. The enzymes share 73% sequence homology and follow the same kinetic and chemical mechanism but have different substrate and inhibitor specificities. Chemical modification experiments provide evidence that a histidine residue is essential for the catalysis. There is also strong evidence that two cysteine residues are present in the active site of MAO. 

Newly formed collagen extracted with cold, aqueous NaCl solutions consists of three equal-sized chains (a-components) of two different composition types ( -l and -2). The two chains of similar composition are the a-1 chains. The a-2 chain differs from the a-1 in a number of amino acids, particularly hydroxyproline, proline, lysine, and histidine (26). As the collagen molecule matures, the a-chains crosslink intramo-lecularly in pairs this older protein can be readily extracted with acidic solutions such as dilute acetate and citrate buffer, but not with salt solutions. The crosslinked chains are called /3 components the crosslinks are probably covalent bonds (26) that arise by condensation of the side chains of strategic lysyl residues after enzymatic oxidative deamination. Older collageil also forms intermolecular bonds, but the nature of this crosslink has not yet been determined (27). 

Metabolism. Histamine is formed from the amino acid histidine and is inactivated largely by deamination and by methylation. In common with other local hormones, this process is extremely rapid. 

Amino acids such as serine and histidine are deaminated non-oxidatively... 

Histidine (his) is first deaminated, then the ring is opened and the formamino group is then donated to the one-carbon pool (see later). Two of these reactions are irreversible so his is essential. 

Histidine. Histidine is converted to glutamate in four reactions a nonox-idative deamination, two hydrations, and the removal of a formamino group (NH=CH—) by THF. 

Histidine ammonia-lyase is the first enzyme in the degradation pathway of L-histidine and catalyzes the nonoxidative deamination of histidine (12) to form w r-urocanic acid (13) plus ammonia (Equation (3)). Histidine ammonia-lyase is present in several bacteria and in animals. The mechanism for the reaction that is catalyzed by histidine ammonia-lyase is presumed to be similar to that described above for phenylalanine ammonia-lyase (see Scheme 3). 

All amino acids are not affected to the same extent. Bergel and Bolz28 found that leucine is oxidized ten times faster than alanine. Fiirth29 reports that histidine and proline are relatively stable, and Wunderly30 finds that the deaminating effect is specific for the true amino grouping. 

In addition to glutamate, a number of amino acids release their nitrogen as NH4 (see Fig. 38.5). Histidine may be directly deaminated to form NH4 and urocanate. The deaminations of serine and threonine are dehydration reactions that require pyridoxal phosphate and are catalyzed by serine dehydratase. Serine forms pyruvate, and threonine forms a-ketobutyrate. In both cases, NH4 is released. 

G-values of ammonia were measured after reduction of amino-acids and peptides (7, 9), and of some proteins such as histones that contain relatively low amount of sulfur residues and histidines (26 ). They may reach the G(e aq) value. The high reactivity of e aq toward peptidic bonds is also responsible for the progression of the rate constant with the number of carbonyl groups in small peptides (table 1). The deaminated radical was observed by pulse radiolysis (absorption maximum around 430 run, extinction coefficient at this wavelength ca. 1100 mol 1 cm (3). 

Lipoxygenase (LOX) converts polyunsaturated fatty acids, such as linoleic and linolenic acids, to lipid hydroperoxides (Figure 2)(52,73,74). The lipid hydroperoxides then form hydroperoxide radicals, epoxides, and/or are degraded to form malondialdehyde. These products are also strongly electrophilic, and can destroy individual amino acids by decarboxylative deamination (e.g., lysine, cysteine, histidine, tyrosine, and tryptophan) cause free radical mediated cross-linking of protein at thiol, histidinyl, and tyrosinyl groups and cause Schiff base formation (e.g., malondialdehyde and lysine aldehyde) (39,49,50,74-78). 

The amino acids of animal tissue are involved in other reactions (1) oxidative deamination (2) non-oxidative decarboxylation (3) transamination (4) protein synthesis. Oxidative deamination is important only with respect to L-glutamate, which can be converted to 2-oxogJutarate and ammonia by glutamate dehydrogenase. Decarboxylation is confined to a few amino acids in animal tissue, notably glutamate, histidine, and (after hydroxylation) tryptophan and phenylalanine. In all cases, the products are potent pharmacological agents discussed under autocoid metabolism. Serine is also decarboxylated to ethanolamine, an important reaction which is referred to later in connection with transamination. 

Deamination removal of the amino group (-NH ) from a chemical compound (usually an amino acid). MetaboUcally, D. may occur by a) oxidative D. of amino acids to ketoacids and ammonia by Flavin enzymes (see) and pyridine nucleotide enzymes (see Amino acids, Table 3) b) Transamination (see) in which an amino group is transferred fiom an amino to a keto compound, and c) removal of ammonia from a compound, leaving a double bond, e.g. the D. of L-aspartate to marate, and the D. of histidine to urocanic acid. IVansamination is important in the synthesis of amino acids from tricarboxylic acid cycle intermediates the reverse reactions feed excess amino acids into the tricarboxylic acid cycle for oxidation. 

Lipid oxidation products can interact with proteins and amino acids, and can affect the flavor deterioration and nutritive value of food proteins. Peroxyl radicals are very reactive with labile amino acids (tryptophane, histidine, cysteine, cystine, methionine, lysine and tyrosine), undergoing decarboxylation, decarbonylation and deamination. Methionine is oxidized to a sulfoxide combined cysteine is converted to cystine to form combined thiosulfinate (Figure 11.4). Aldehydes, dialdehydes and epoxides derived from the decomposition of hydroperoxides react with amines to produce imino Schiff bases (R-CH=N-R ). Schiff bases polymerize by aldol condensation producing dimers... 

Direct deamination of AMP to IMP by adenylate aminohydrolase (EC 3.5.4.6) occurs primarily in mammalian systems. It plays little, if any, role in bacteria where conversion usually occurs indirectly via deamination of adenine or adenosine [113,114]. Little is known about regulation at these levels, although adenosine deaminase is inducible by its substrate [114] and mutants lacking it have been obtained [115], Another indirect conversion in bacteria involves the regeneration of AlCAR, in the eventual conversion of phosphoribosyl-ATP (PR-ATP) to histidine. The AlCAR so obtained reenters the biosynthetic pathway and IMP is produced [33]. This pathway is regulated by histidine which exerts a profound feedback inhibition at the level of PR-ATP formation from ATP [116]. 

These homodimeric enzymes, that are present in both prokaryotic and eukaryotic organisms, contain one Cu ion and one redox-active cofactor topaquinone (TPQ) per monomer [5, 6]. They catalyze the oxidative deamination of primary amines [7-9]. The Cu(ll) ion is coordinated by three histidine residues and three water molecules (Fig. 11.1). The TPQ cofactor is not far from the Cu ion. The process can be divided into an initial reductive reaction followed by an oxidative step, based on the redox state of TPQ the Cu ion is thought to be involved in the formation of the TPQ semiquinone through reduction of Cu(II) to Cu(I). An alternative hypothesis has been recently proposed where the copper ion stays as Cu(II) and the one-electron reduction of O2 is carried out by a modified amino-resorcinol TPQ cofactor. The Cu(II) would provide electrostatic stabilization to the superoxide anion intermediate [10-12]. The reduction of molecular oxygen would result in weakly Cu-bormd hydroperoxide which is subsequently displaced by a water molecule, gets protonated and it is eliminated as hydrogen peroxide. 

Histamine is synthesized from L-histidine by the indncible enzyme L-histidine decarboxylase and inactivated by histamine Af-methyltransferase-eatalyzed methylation of the imidazole ring and oxidative deamination of the primary amino gronp catalyzed by diamine oxidase. 

Lysozyme of mink spleen, kidneys, and liver has been isolated by affinity chromatography on deaminated chitin. The L-histidine content of the enzyme was unusually high. The lysozyme preparations contained an unknown, firmly bound component which absorbed at 400—420 nm. 

Brief reference will be made to the following papers which have appeared since this chapter was written. Partially purified Neurospora L-serine dehydrase has been studied. Both L-serine and L-threonine appear to be deaminated by the same enzyme. The enzymatic pathway of histidine degradation in liver has been investigated. Soluble gluta-minase I has been prepared. Additional eiddence for the Avide scope of transamination has appeared. The presence of an ornithine-a-keto-glutarate transaminase in neurospora has been demonstrated. Transamination of non-a-amino acids has been demonstrated in brain in... 

The Japanese investigators " - proposed an alternate pathway, namely, that histidine was first deaminated to urocanic acid by an enzyme named by them histidine deaminase, and the urocanic acid, in... 

A new procedure for the determination of urocanic acid has been developed, based on the fact that this compound exhibits a strong absorption in the ultraviolet in the region of 240-280 m/i. This can be employed both to demonstrate the formation of urocanic acid and as a method of assay for the enzyme deaminating histidine to urocanic acid. With this test method it has been shown that urocanic acid accumulates when histidine is incubated with liver extract or with extracts of acetone-dried liver powder. Mehler and Tabor determined that the activity of the enzyme forming urocanic acid appeared to be sufficient to account for the total histidine degradation of liver extracts, as judged by the rate of formation of urocanic acid. 

In Pseudomonas fluorescens extract, histidase free from urocanase can be prepared by heating the extract at 85°C. for 15 minutes. By this procedure all ability to destroy urocanic acid is lost, but the full capacity to deaminate histidine is retained when the product is supplemented with 10 M glutathione. 

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