Hydro-lyases

Aconitase [citrate(isocitrate) hydro-lyase, EC 4.2.1.3] is the second enzyme of the citric acid cycle, which plays a central role in metabolism for all aerobic organisms. This enzyme catalyzes a dehydration-rehydration reaction interconverting citrate and 2R,3S-isocitrate via the allylic intermediate ds-aconitate. 

Is aconitase unique or are there other hydro-lyases which utilize Fe-S clusters as catalytic groups A list of enzymes of the hydro-lyase class that recently have been discovered to be Fe-S proteins is found in Table VI. 

Table VI. Enzymes of the Hydro-Lyase Class that are Fe-S Proteins...

This [4Fe-4S] cluster-containing enzyme [EC 4.2.1.3], also known as citrate hydro-lyase and aconitate hydra-tase, will act on citrate to generate ds-aconitate ((Z)-prop-l-ene 1,2,3-tricarboxylate) and water. The enzyme will also catalyze the conversion of isocitrate into ds-aconitate. 

This enzyme [EC 4.2.1.33], also referred to as isopropyl-malate hydro-lyase, catalyzes the conversion of 3-isopro-pylmalate to 2-isopropylmaleate and water. 

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. 

The systematic name for carbonic anhydrase is carbonate hydro-lyase, and its numerical code is EC. 4.2.1.1. The first number identifies it as a lyase the second as an enzyme that catalyzes the breakage of a carbon-oxygen bond, leading to unsaturated products and the third as a hydro-lyase, participating in a reaction involving the elimination of water. The last number is the specific serial number assigned to this enzyme. In this text, the trivial names are used. Names of a selected list of clinically useful enzymes with their EC codes, systematic names, other common names, and abbreviations are given in Appendix V. 

The addition of water to carbon-carbon double bonds is a reaction that is catalyzed by lyases belonging to the subclass of the hydro-lyases (E.C. 4.2.1.-), which have been grouped under the carbon-oxygen lyases. Not all members of this subgroup are capable of water addition to carbon-carbon double bonds. Nitrile hydratase (E. C. 4.2.1.84, discussed in Section 12.1) for instance, is categorized in this subclass and catalyzes the addition of water to nitriles. The nomenclature of the hydro-lyases subgroup, which contains hydratases and dehydratases, does not preclude any direction of the reaction, but rather reflects the context in which the enzyme was originally discovered. 

The addition of water to carbon-carbon double bonds is very common to biology, and a large variety of enzymes from different sources representing almost a hundred different hydro-lyase types have been characterized biochemically. Hydro-lyases are for instance involved in the metabolism of a variety of carbohydrates and play a prominent role in fatty acid synthesis and degradation as well. Despite the abundant presence of hydro-lyases in nature, however, applications of these enzymes in organic chemical synthesis are not as widespread. This is mainly due to the limited availability of these enzymes and the fact that many of the enzymes cannot easily be stably maintained during catalysis. 

The enzymatic reactions in which adenosylcobalamin was known to serve as coenzyme by 1964 were those of glutamate mutase, methylmalonyl-CoA mutase (MCM), " propane-1,2-diol hydro-lyase (dioldehydrase, DDH), and glycerol hydro-lyase (glycerol dehydrase), shown in Equations (1)—(4). 

Aconitase (citrate(isocitrate)hydro-lyase) catalyzes the isomerization of citrate and isocitrate via cM-aconitate, as shown in Figure 2. The reaction is stereospecific, as shown, with the hydration reactions occurring in a trans orientation across the double bond. Also as shown, the H... 

L-Tryptophan synthase, tryptophan desmolase, L-serine hydro-lyase (adding imhleglycerol-phos-phate) (EC 4.2.1.20) the enzyme catalysing the synthesis of L-tryptophan from L-serine and indole 3-glycerol phosphate. T.s. from E. coli (M, 149,000) and other prokaryotes has 02 subunit composition. The enzyme separates easily into monomeric subunit a (also called protein B, M, 29,000) and dimeric subunit 02 (also called protein B Af, of dimer 90,000) when eluted from DEAE cellulose with a sodium chloride gradient. The separated subunits catalyse partial reactions of L-tryptophan synthesis ... 

The fifth enzyme activity, tryptophan synthetase [EC 4.2.1.20, L-serine hydro-lyase (adding indole)], catalyzes the final step in tryptophan synthesis. It consists of a complex of two nonidentical protein subunits, B (/ -chains) and A (a-chains) [7,14,38-41], which are coded for by the fourth and fifth tryptophan genes, respectively, in E. coli [14] and S. typhimurium [27]. The A subunit has been purified and shown to be a single polypeptide a-chain [42]. Wilson and Crawford [39] purified the B-protein subunit. Their conclusion that it was a dimer P2) which complexed with two a-chain subunits to form the tryptophan synthetase ( 2 Pi) is supported by other studies of the subunits and their association [40,41], The two proteins of tryptophan synthetase (TS) can catalyze the following reactions [38,43]. 

Carbonic anhydrase sulphate bile salts sulphotransferase Carbonate hydro-lyase 4.2.1.1 225... 

The major developmental change which takes place In both brain and liver is the postnatal activation of the transsulfuration pathway of methionine metabolism. The net result of this pathway is the transfer of the sulfur atom from homocysteine to the carbon skeleton of serine to form cysteine. This conversion is mediated by two enzymes cystathionine synthase (L-serine hydro-lyase adding homocysteine, EC 4.2.1.22) which catalyzes the 3-activation of serine and the addition of homocysteine to form the thio-ether, cystathionine cystathionase (EC 4.4.1.1) which catalyzes the y-cleavage of cystathionine to form cysteine (Fig. 1). Both of these enzymes catalyze reactions other than those described above although their importance vivo is uncertain (Tallan et al., 1974). In mature mammals, activities both of cystathionine synthase and of cystathionase are present in brain and liver, although cystathionase activity in... 

The mechanism of the inhibitory effect of FA on aconitase (citrate (isocitrate) hydro-lyase, EC 4.2.1.3) is one of the most interesting in biochemistry. Upon entering an organism, nontoxic FA xmdergoes a series of metabolic conversions, the result of which is synthesis of higWy toxic FC this process was termed lethal si/nthesis (Peters, 1952). FC is formed by the enz3miahc condensation of fluoroacetyl-CoA with oxaloacetate, catalyzed by citrate... 

Engeland K, Kindi H. Evidence for a peroxisomal fatty acid 8-oxldatlon involving D-3-hydroxyacyl-Ck)As. Characterization of two forms of hydro-lyase that convert D-(-)-3-hydroxyacyl-CoA into 2-fra/7s-enoyl-CoA. Eur J Biochem 1991 200 171 -178. 

Biochemical Aspects. The zinc-containing metalloenzyme carbonic anhydrase (carbonic hydro-lyase, EC 4.2.1,1) is specifically inhibited by univalent anions and by aromatic sulphonamides. AfT (25 for the binding reactions between bovine carbonic anhydrase and 3-methyl-2-acetylimino-l,3,4-thiadiazoline-5-sulphonamide (Methazolamide) is — 59.0kJmol and that for 5-phenyl-sulphonamido-l,3,4-thiadiazole-2-sulphonamide (CL 11366) is — 57.7kJmol" The thermodynamic quantities did not correlate with the assumed structural features of the binding process. ... 

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