Enzyme and promoters

ALA synthase is a pyridoxal phosphate-dependent enzyme and promotes Schiff-base formation between its coenzyme and glycine (67 in Fig. 37). Nucleophilicity at C-2 of the glycine could be generated either by decarboxylation or by abstraction of a proton. In the first case 5-aminolaevulinic acid would retain both methylene protons of glycine, in the second, one of the protons would be lost to the medium (Fig. 37). Acylation of the pyridoxal-bound intermediate (68 or 69) by succinyl-CoA would constitute the next step and this could be followed either by direct hydrolysis of the Schiff-base or by decarboxylation with subsequent hydrolysis depending on which course was chosen in the first stage of the reaction. 

Metal cofactors in enzymes may be bound reversibly or firmly. Reversible binding occurs in metal-activated enzymes (e.g., many phosphotransferases) firm (or tight) binding occurs in metalloenzymes (e.g., carboxypeptidase A). Metals participate in enzyme catalysis in a number of different ways. An inherent catalytic property of a metal ion may be augmented by the enzyme protein, or metal ions may form complexes with the substrate and the active center of the enzyme and promote catalysis, or metal ions may function in electron transport reactions between substrates and enzymes. 

Enzyme A protein that funetions as a bioeatalyst in a ehemieal reaetion. Any group of eatalytie proteins that are produeed by living eells mediating and promoting the ehemieal proeesses of life without... 

The low content of water in these formulations promotes improved stabilization of enzyme and bleach additives. The combination of LAS and AE in a low-water-content formulation is effective at solubilizing enzymes and preserving enzyme stability when the sum of the LAS and water levels ranges between 25% and 45% [53],... 

N-Acetylneuraminic acid aldolase (or sialic acid aldolase, NeuA EC 4.1.3.3) catalyzes the reversible addition of pyruvate (2) to N-acetyl-D-mannosamine (ManNAc (1)) in the degradation of the parent sialic acid (3) (Figure 10.4). The NeuA lyases found in both bacteria and animals are type I enzymes that form a Schiff base/enamine intermediate with pyruvate and promote a si-face attack to the aldehyde carbonyl group with formation of a (4S) configured stereocenter. The enzyme is commercially available and it has a broad pH optimum around 7.5 and useful stability in solution at ambient temperature [36]. 

Globular proteins are compact, are roughly spherical or ovoid in shape, and have axial ratios (the ratio of their shortest to longest dimensions) of not over 3. Most enzymes are globular proteins, whose large internal volume provides ample space in which to construct cavities of the specific shape, charge, and hy-drophobicity or hydrophilicity required to bind substrates and promote catalysis. By contrast, many structural proteins adopt highly extended conformations. These fibrous proteins possess axial ratios of 10 or more. 

Acetyl-CoA carboxylase is an allosteric enzyme and is activated by citrate, which increases in concentration in the well-fed state and is an indicator of a plentiful supply of acetyl-CoA. Citrate converts the enzyme from an inactive dimer to an active polymeric form, having a molecular mass of several milhon. Inactivation is promoted by phosphorylation of the enzyme and by long-chain acyl-CoA molecules, an example of negative feedback inhibition by a product of a reaction. Thus, if acyl-CoA accumulates because it is not esterified quickly enough or because of increased lipolysis or an influx of free fatty acids into the tissue, it will automatically reduce the synthesis of new fatty acid. Acyl-CoA may also inhibit the mitochondrial tricarboxylate transporter, thus preventing activation of the enzyme by egress of citrate from the mitochondria into the cytosol. 

However, the most common and important method of synthesis of chiral non-racemic hydroxy phosphoryl compounds has been the resolution of racemic substrates via a hydrolytic enzyme-promoted acylation of the hydroxy group or hydrolysis of the 0-acyl derivatives, both carried out under kinetic resolution conditions. The first attempts date from the early 1990s and have since been followed by a number of papers describing the use of a variety of enzymes and various types of organophosphorus substrates, differing both by the substituents at phosphorus and by the kind of hydroxy (acetoxy)-containing side chain. 

Immunohistochemical studies carried out in our laboratories have demonstrated the presence of xanthine oxidase in synovial endothelial cells (Stevens etal., 1991). As expected, the activity of this enzyme per unit weight of tissue is generally higher in synovia taken from RA patients due to their increased vascularity (Allen et al., 1987). In addition, it has also been shown that rheumatoid synoviocytes contain increased levels of iron-saturated ferritin (Morris et d., 1986). Xanthine oxidase (but not dehydrogenase) is able to mobilize iron from ferritin, supplying the necessary transition metal catalyst for the Haber-Weiss reaction and promoting OH formation (Biemond eta/., 1986). 

Furthermore, depletion of hepatic GSH induced chemically or by fasting augmented hepatic I/R-induced enzyme release and promoted lipid peroxidation (Jennische, 1984 Stein et al., 1991) Benoit et al. (1992) have used portacaval-shunted rats as a model of chronic hepatic ischaemia, and were able to show decreases in total levels of SOD and xanthine dehydrogenase, but no significant change in catalase or glutathione peroxidase. 

---