Cysteine deamination

Other than water, protein is the major constituent of meat averaging nearly 21% in heef or chicken meat, with fat varying fiom 4.6 to 11.0% in beef and fiom 2.7 to 12.6% in chickoi. The principal radiolytic reactions of aqueous solutions of aliphatic amino acids are reductive deamination and decarboxylation. Alanine yields NH3, pyruvic add, acetaldehyde, propionic acid, CO2, H2, and ethylamine (6). Sulfur-containing amino adds are espedally sensitive to ionizing radiation. Cysteine can be oxidized to cystine by the hydroxyl radical or it can react with the hydrated electron and produce... 

When present in excess methionine is toxic and must be removed. Transamination to the corresponding 2-oxoacid (Fig. 24-16, step c) occurs in both animals and plants. Oxidative decarboxylation of this oxoacid initiates a major catabolic pathway,305 which probably involves (3 oxidation of the resulting acyl-CoA. In bacteria another catabolic reaction of methionine is y-elimination of methanethiol and deamination to 2-oxobutyrate (reaction d, Fig. 24-16 Fig. 14-7).306 Conversion to homocysteine, via the transmethylation pathway, is also a major catabolic route which is especially important because of the toxicity of excess homocysteine. A hereditary deficiency of cystathionine (3-synthase is associated with greatly elevated homocysteine concentrations in blood and urine and often disastrous early cardiovascular disease.299,307 309b About 5-7% of the general population has an increased level of homocysteine and is also at increased risk of artery disease. An adequate intake of vitamin B6 and especially of folic acid, which is needed for recycling of homocysteine to methionine, is helpful. However, if methionine is in excess it must be removed via the previously discussed transsulfuration pathway (Fig. 24-16, steps h and z ).310 The products are cysteine and 2-oxobutyrate. The latter can be oxidatively decarboxylated to propionyl-CoA and further metabolized, or it can be converted into leucine (Fig. 24-17) and cysteine may be converted to glutathione.2993... 

These reactions, which have provided a means of inhibiting the flavin-linked monoamine oxidases, enable us to end on a clinical note. The monoamine oxidases are responsible for the deamination of monoamines such as adrenaline, noradrenaline, dopamine, and serotonin, which act as neurotransmitters. Imbalances in the levels of monoamines cause various psychiatric and neurological disorders Parkinson s disease is associated with lowered levels of dopamine, and low levels of other monoamines are associated with depression. Inhibitors of monoamine oxidases may consequently be used to treat Parkinson s disease and depression. The flavin moiety is covalently bound to the enzyme by the thiol group of a cysteine residue (equation 9.17). The acetylenic suicide inhibitor N,N-dimethyl-propargylamine inactivates monoamine oxidases by alkylating the flavin on N-5.25 A likely mechanism for the reaction is the Michael addition of the N-5 of the reduced flavin to the acetylenic carbon 2... 

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. 

Heterocyclic compounds are dominant among the aroma compounds produced in the Maillard reaction, and sulfur-containing heterocyclics have been shown to be particularly important in meat-like flavors. In a recent review, MacLeod (6) listed 78 compounds which have been reported in the literature as possessing meaty aromas seven are aliphatic sulfur compounds, the other 71 are heterocyclic of which 65 contain sulfur. The Strecker degradation of cysteine by dicarbonyls is an extremely important route for the formation of many heterocyclic sulfur compounds hydrogen sulfide and mercaptoacetaldehyde are formed by the decarboxylation and deamination of cysteine and provide reactive intermediates for interaction with other Maillard products. 

Free amino acids readily form chloramines in reactions with HOC1. However, the reaction can be postponed by the presence of amino acids whose side groups have reducing properties (as is the case with cysteine, methionine, and tryptophan). Amino acid chloramines located at the a-carbon are unstable, decomposing by deamination and decarboxylation. The final stable products are ammonia, chloride, and the aldehyde respective to the amino acid carbon backbone (H12, Z4) ... 

In addition to being a precursor of methionine in the activated methyl cycle, homocysteine is an intermediate in the synthesis of cysteine. Serine and homocysteine condense to form cystathionine. This reaction is catalyzed hy cystathionine -synthase. Cystathionine is then deaminated and cleaved to cysteine and a-ketohutyrate hy cystathioninase. Both of these enzymes utilize PLP and are homologous to aspartate aminotransferase. The net reaction is... 

Fig. 1.8 Asaccharolytic fermentation produces ammonia and short-chain fatty acids. This group of fermentations by oral bacteria utilizes proteins, which are converted to peptides and amino acids. The free amino acids are then deaminated to ammonia in a reaction that converts nicotinamide adenine dinucleotide (NAD) to NADH. For example, alanine is converted to pyruvate and ammonia. The pyruvate is reduced to lactate, and ammonium lactate is excreted into the environment. Unlike lactate from glucose, ammonium lactate is a neutral salt. The common end products in from plaque are ammonium acetate, ammonium propionate, and ammonium butyrate, ammonium salts of short chain fatty acids. For example, glycine is reduced to acetate and ammonia. Cysteine is reduced to propionate, hydrogen sulfide, and ammonia alanine to propionate, water, and ammonia and aspartate to propionate, carbon dioxide, and ammonia. Threonine is reduced to butyrate, water, and ammonia and glutamate is reduced to butyrate, carbon dioxide, and ammonia. Other amino acids are involved in more complicated metabolic reactions that give rise to these short-chain amino acids, sometimes with succinate, another common end product in plaque.

The deamination of xenobiotic cysteine conjugates can lead to thlo-acetlc acid conjugates, as observed with PCNB In peanut (100). or thlo-lactlc acid conjugates, as observed with EPTC In corn and cotton (106) or PCNB In peanut (WO). Cysteine conjugates can also undergo 8-lyase cleavage to thioalcohols, as observed with PCNB In peanut (WO). The thioalcohols can be methylated by an S-adenosyl-methlonlne methyltransferase system, as demonstrated with an In vitro enzyme system derived from onion root (J01 ). Pentachloro-... 

Cystathionine-y-synthase isolated from Salmonella typhimurium is a tetramer (molecular weight 160000) and catalyses, in vivo, the y-replacement of O-suc-cinylhomoserine with cysteine [79] to yield cystathionine. The latter, by way of homocysteine, is involved in the biosynthesis of methionine. In other species of bacteria and plants the succinyl moiety may be replaced by acetyl, phosphoryl, or malonyl moieties [80]. In the absence of cysteine the enzyme catalyses an abnormal reaction resulting in the formation of a-oxobutyrate. The latter reaction has been utilised for mechanistic investigations pertinent to the y-eUmination-deamination process (vide infra). 

The first preparations of optically active thiirancarboxylic acids have been reported.Treatment of the cysteine esters (i )-(321 R = Me) with NaN02 and HCl causes deaminative cyclization to chiral (5)-(322 R = Me). For the parent acid (R)-(321 R = H), optical yields of (5)-(322 R = H) of 53 and 60% were obtained in dilute HCl or MeC02H, respectively. 

The Strecker degradation involves the oxidative deamination and decarboxylation of a a-amino acid in the presence of a dicarbonyl compound. The products formed from this reaction are an aldehyde containing one less carbon atom than the original amino acid and an a-aminoketone (Table 9.2). The Strecker degradation of methionine and cystein is a source of sulfur-containing intermediates (e.g hydrogen sulfide and 2-methylthiopropanal = methional) [48]. 

They catalyse rate-limiting steps in the pathway and are important control points. Glucogenic intermediates of the tricarboxylic acid cycle and amino acids that are transaminated or deaminated to tricarboxylic acid intermediates do not require pyruvate carboxylase (Fig. 3.1). Pyruvate and metabolites such as lactate, alanine, serine, glycine, cysteine that are converted into pyruvate require all four enzymes (Fig. 3.1). Gluconeogenesis is often linked to glycogen synthesis catalysed by glycogen synthase (see Section 3.5). 

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). 

Recently, the chemical synthesis of 5/i-3-phosphatidylsulfocholine has been reported (Tremblay and Kates, 1979). Biosynthesis of the sulfocholine moiety in Nitzschia alba has been suggested to occur via the deamination, oxidative decarboxylation, and methylation of methionine. In addition, the 1-deoxyceramide-1-sulfonate compound was proposed to be synthesized in a manner analogous to sphingosine, with cysteine replacing serine (Anderson et a/., 1979). 

It was suggested that dimerization of thiyl radicals to give disulphide occurred mainly on dissolution of the irradiated solid. In the case of cysteamine hydrochloride, where there is no carbonyl group to trap the electron prior to deamination, it was found that (7(NH3)<0 1. In spite of this G(H2S) was only 1-2, lower than for cysteine, but the value of (Ha) of 5-1 was much higher. This is the same situation as was found for mercaptoethanol but not for cysteamine itself in aqueous solution. 

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