L-Histidine ammonia lyase

A specialized amino acid residue that serves as an essesn-tial electrophilic center in several enzymatic reactions, including those catalyzed by L-phenylalanine ammonia lyase (Reaction L-phenylalanine tranx-cinnamate + NH3) and L-histidine ammonia lyase (Reaction L-histi-dine urocanate + NH3). The former facilitates the elimination of ammonia and the pro-S hydrogen of phe-nylanine, and the initial step is nucleophilic attack of... 

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,... 

L-Histidine ammonia-lyase kckKomoboidtdJt tiqLiidiim L-Histidine Urocanic acid NHa, 180 (37 C) 12... 

Lyases involve elimination reactions in which a group of atoms is ranoved from the substrate. These catalytic reactions require the addition of groups to a double bond or the formation of a double bond (e.g., C=C, C=N, C=0). This includes the aldolases, decarboxylases, dehydratases, and some pectinases but does not include hydrolases. An example is the histidine ammonia-lyase (EC 4.3.1.3 systematic name, L-histidine ammonia-lyase, which is also called histidase) reaction with its products, shown in Figure 4.7. 

Chemical inhibition of L-phenylalanine ammonia lyase activity may be achieved by the use of typical carbonyl reagents such as sodium borohydride and potassium cyanide. Treatment of the enzyme with tritiated sodium borohydride and subsequent hydrolysis gave alanine in which the majority of the radioactivity was confined to the jj-methyl group . Similarly reaction with potassium cyanide and hydrolysis gave aspartic acid labelled exclusively in the -carboxyl group . These observations led to the proposal that the active site of the enzyme, like that of the related L-histidine ammonia lyase , contains a dehydro-alanine residue... 

Active immobilized L-histidine ammonia lyase for the continuous production of urocanic acid... 

Considerable progress has been made with elucidating the functional aspects of the PAL protein, assisted by the availability of the crystal structure for histidine ammonia lyase (HAL), which catalyzes a reaction similar to that of PAL, the conversion of L-histidine to... 

R.R. Walters, P.A. Johnson and R.P. Buck, Histidine ammonia-lyase enzyme electrode for determination of L-histidine, Anal. Chem., 52 (1980) 1684-1690. 

Histidine ammonia lyase (HAL, histidinase, histidine-a-deaminase, E.C. 4.3.1.3) is capable of abstracting ammonia from L-histidine (17), resulting in the formation of urocanoic acid [Scheme 12.6-4, (6)], an intermediate in the metabolism of l-histidine,n). HAL has also been identified as a key enzyme in the synthesis of secondary metabolites such as Nikkomycin in Streptomyces tendae,ul The mechanism of the enzyme has been investigated and seems to proceed via the carbanion intermediate111, 13]. Synthetic applications of HAL are difficult to achieve, particularly as the enzyme is sensitive to oxygen1131. The utility of HAL is limited to niche applications such as the synthesis of radiolabeled urocanic acids as tracers of histidine metabolism1"1. 

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). 

FIGURE 4.7 The histidine ammonia-lyase reaction L-histidine and its products urocanateH-ammonia. 

Brand, L.M., and A.E. Harper (1976). Histidine ammonia-lyase from rat liver. Purification, properties and inhibition by substrate analogues. Biochemistry, 15, 1814-1821. 

The main pathway of L-histidine degradation includes formation of urocanic acid and leads to glutamic acid (Fig. 241). Histidine ammonia-lyase (like phenylalanine ammonia-lyase, D 22.2.1) catalyzes the transelimination of the NH2-group and a jff-hydrogen atom. Of minor importance in L-histidine degradation is the formation and further degradation of imidazole pyruvic acid. 

The aromatic amino acid L-phenylalanine (primary metabolite) is directed into the phe-nylpropanoid pathway leading to hydroxy-cinnamic acids, lignin and flavonoids by the activity of L-phenylalanine ammonia-lyase (PAL), which brings about its nonoxidative deamination yielding ammonia and tvans-cinnamic acid (Fig. 1). PAL is one of the most studied plant enzymes, and its crystal structure has recently been solved [2]. PAL is related to the histidine and tyrosine ammonia-lyases of amino acid catabolism. A class of bifunctional PALs found in monocotyle-donous plants and yeast can also deaminate tyrosine [3]. A single His residue is responsible for this switch in substrate preference [3, 4]. All three enzymes share a unique MIO (4-methylidene-imidazole-5-one) prosthetic group at the active site. This is formed auto-catalytically from the tripeptide Ala-Ser-Gly by cyclization and dehydration during a late... 

Dehydroalanine units have been identified at the active sites of the enzymes histidine ammonia lyase 144,434) and L-phenylalanine ammonia lyase (164), either by reduction with NaB Ht (164, 434), or by addition of nitromethane (144) and subsequent reduction to the amine. Following hydrolysis it was possible to detect tritiated alanine or a,y-diamino-butyric acid respectively. 

A PNH3 electrode covered with this enzyme is used [123] for the determination of L-phenylalanine with very little interference fiom otho amino acids, notably L-tyrosine. A similar selectivity is obtained with phenylalanine decarboxylase [103] which, when attached to a pC02 electrode, enables the specific determination of phenylalanine. Other ammonia lyases are used te determine amino acids. Methionine lyase [124] and histidine ammonia lyase [12S] produce ammonia which is detected with a PNH3 electrode. 

Decarboxylases of phenylalanine, tyrosine, and lysine and ammonia lyases of histidine, glutamine, and asparagine are also highly selective. Guilbault et al. (1988) described a potentiometric enzyme sensor for the determination of the artificial sweetener aspartame (L-aspartyl-L-phen-ylalanine methylester) based on L-aspartase (EC 4.3.1.1). The ammonia liberated in the enzyme reaction created a slope of 30 mV/decade for the enzyme-covered ammonia sensitive electrode. The specificity of the sensor was excellent however, the measuring time of 40 min per sample appears not to be acceptable. The measuring time has been decreased to about 20 min by coimmobilizing carboxypeptidase A with L-aspartase (Fatibello-Filho et al., 1988). 

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