Ammonia elimination enzymic

Pyridoxal Phosphate Reaction Mechanisms Threonine can be broken down by the enzyme threonine dehydratase, which catalyzes the conversion of threonine to a-ketobutyrate and ammonia. The enzyme uses PLP as a cofactor. Suggest a mechanism for this reaction, based on the mechanisms in Figure 18-6. Note that this reaction includes an elimination at the j8 carbon of threonine. 

A large group of pyridoxal-P-dependent enzymes catalyse reactions that affect as well as C of the amino acid and these can be divided into two main groups (Fig. 24) (a) those that involve the substitution of a group at ()8 replacement) and (b) those that involve the overall elimination of the a-hydrogen atom and the substituent with the formation of a-oxoacid and ammonia elimination-deamination). 

This enzyme [EC 4.4.1.6] catalyzes the pyridoxal-phos-phate-dependent hydrolysis of an 5-alkyl-L-cysteine to generate an alkyl thiol, ammonia, and pyruvate. The reaction is an a,/3-elimination. In yeast, the enzyme may be identical to cystathionine /3-lyase. See also Alliin Lyase... 

This pyridoxal-phosphate-dependent enzyme [EC 4.2.99.9], also known as cystathionine y-synthase, catalyzes the reaction of O-succinyl-L-homoserine with L-cysteine to produce cystathionine and succinate. The enzyme can also use hydrogen sulfide and methanethiol as substrates, producing homocysteine and methionine, respectively. In the absence of a thiol, the enzyme can also catalyze a /3,y-elimination reaction to form 2-oxobu-tanoate, succinate, and ammonia. 

This enzyme [EC 4.1.99.1], also known as L-tryptophan indole-lyase, catalyzes the hydrolysis of L-tryptophan to generate indole, pyruvate, and ammonia. The reaction requires pyridoxal phosphate and potassium ions. The enzyme can also catalyze the synthesis of tryptophan from indole and serine as well as catalyze 2,3-elimination and j8-replacement reactions of some indole-substituted tryptophan analogs of L-cysteine, L-serine, and other 3-substituted amino acids. 

PAL is one of the best-characterized enzymes of plant secondary metabolism. It converts l-phenylalanine into tran -cinnamate ( -cinnamate) by the tra 5-elimination of ammonia and the pro-StS proton (see Ref. 4 for a full reaction discussion). The enzyme, which requires no cofactor, is a tetramer of 310-340 kDa. A cDNA for PAL was first isolated from Petrose-linum crispum (parsley), and others have subsequently been isolated from numerous species. Often PAL is produced from a multigene family and is present in a variety of isoenzyme forms. 

The lyases comprise enzyme class 4. They are enzymes cleaving C-C, C-0, C-N and other bonds by elimination, not by hydrolysis or oxidation. Lyases also catalyse addition to donble bonds. The types of reactions catalysed by lyases are decarboxylation (decarboxylase), hydration/dehydration (hydratase/dehydratase), ammonia addition/deamination (ammonia-lyase), cyanohydrin formation/cleavage (oxynitrilase),... 

In the urea cycle, two molecules of ammonia combine with a molecule of carbon dioxide to produce a molecule of urea and water. The overall cycle involves a series of biochemical reactions dependent on enzymes and carrier molecules. During the urea cycle the amino acid ornithine (C5H12N202) is produced, so the urea cycle is also called the ornithine cycle. A number of urea cycle disorders exist. These are genetic disorders that result in deficiencies in enzymes needed in one of the steps in the urea cycle. When a urea cycle deficiency occurs, ammonia cannot be eliminated from the body and death ensues. 

Other enzymes that catalyze elimination reactions that produce fumarate are aspartate ammonia-lyase (aspartase),63 argininosuccinate lyase (Fig. 24-10, reaction g),64/65 and adenylosuccinate lyase... 

Fig. 25-15). In every case it is NH3 or an amine, rather than an OH group, that is eliminated. However, the mechanisms probably resemble that of fumarate hydratase. Sequence analysis indicated that all of these enzymes belong to a single fumarase-aspartase family.64 65 The three-dimensional structure of aspartate ammonia-lyase resembles that of fumarate hydratase, but the catalytic site lacks the essential HI 88 of fumarate hydratase. However, the pKa values deduced from the pH dependence of Vmax are similar to those for fumarase.64 3-Methylaspartate lyase catalyzes the same kind of reaction to produce ammonia plus czs-mesaconate.63 Its sequence is not related to that of fumarase and it may contain a dehydroalanine residue (Chapter 14).66... 

Catabolism of histidine in most organisms proceeds via an initial elimination of NH3 to form urocanic acid (Eq. 14-44). The absence of the enzyme L-histidine ammonia-lyase (histidase) causes the genetic disease histidinemia 284/285 A similar reaction is catalyzed by the important plant enzyme L-phenylalanine ammonia-lyase. It eliminates -NH3+ along with the pro-S hydrogen in the (3 position of phenylalanine to form frans-cinnamate (Eq. 14-45). Tyrosine is converted to p-coumarate by the same enzyme. Cinnamate and coumarate are formed in higher plants and are converted into a vast array of derivatives (Box 21-E,... 

The isomerization reactions. At least 10 reactions of the type described by Eq. 16-34 are known397 (Table 16-1). They can be subdivided into three groups. First, X = OH or NH2 in Eq. 16-34 isomerization gives a geminal-diol or aminoalcohol that can eliminate H20 or NH3 to give an aldehyde. All of these enzymes, which are called hydro-lyases or ammonia-lyases, specifically require K+ as well as the vitamin B12 coenzyme. 

A great deal of excess NH3 frequently results from amino acid catabolism. This excess ammonia must be eliminated. In bacteria and lower eukaryotes the ammonia can usually be removed by simple diffusion, but in higher eukaryotes this is not feasible. Since the ammonia is frequently quite toxic, it is detoxified before removal by conversion to urea or uric acid. An intricate pathway resulting in the conversion of ammonia into urea involves five enzymes Three located in the cytoplasm and the remaining two in the mitochondrial matrix. 

Methionine 7-lyase, in contrast, has been purified from Aeromonas sp., Pseudomonas putida and Clostridium sporogenes (361. This enzyme effects a a,y-elimination of methanethiol and ammonia from L-methionine with the direct formation of 2-ketobutyrate ... 

Lyases are an attractive group of enzymes from a commercial perspective, as demonstrated by then-use in many industrial processes.240 They catalyze the cleavage of C-C, C-N, C-O, and other bonds by means other than hydrolysis, often forming double bonds. For example, two well-studied ammonia lyases, aspartate ammonia lyase (aspartase) (E.C. 4.3.1.1) and phenylalanine ammonia lyase (PAL) (E.C. 4.3.1.5), catalyze the trans-elimination of ammonia from the amino acids, l-aspartate and L-phenylalanine, respectively. Most commonly used in the synthetic mode, the reverse reaction has been used to prepare the L-amino acids at the ton scale (Schemes 19.30 and 19.31).240 242 These reactions are conducted at very high substrate concentrations such that the equilibrium is shifted, resulting in very high conversion to the amino acid products. 

In eukaryotic cells, the two enzymes are in different cellular compartments. Form I uses ammonia and is mitochondrial its function is to provide activated ammonia for arginine biosynthesis (and urea formation during Nitrogen elimination). Form II uses glutamine and is cytoplasmic it functions in pyrimidine biosynthesis. 

Many amino acids can lose ammonia to give an unsaturated acid. The enzymes that catalyse these reactions are known as amino acid ammonia lyases. The one that concerns us at the end of the shikimic acid pathway is phenylalanine ammonia lyase, which catalyses the elimination of ammonia from phenylalanine to give the common metabolite cinnamic acid. 

The difficult elimination is accomplished by making it an ammonia transfer reaction rather than an elimination of ammonia. Recycling the enzyme does eventually require elimination of ammonia... 

The 1,2-migration of amino groups in /3-aminoalkyl radicals such as 24 has also been of interest because of the involvement of these species in the enzyme-catalyzed elimination of ammonia from 1,2-amino alcohols.47-50 These studies have also been reviewed recently by Radom et al45... 

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