Threonine aldolases pyridoxal-5 -phosphate-dependent

The metabolism of P-hydroxy-a-amino adds involves pyridoxal phosphate-dependent enzymes, dassified as serine hydroxymethyltransferase (SHMT) (EC 2.1.2.1) or threonine aldolases (ThrA L-threonine selective = EC 4.1.2.5, L-aHo-threonine selective = EC 4.1.2.6). Both enzymes catalyze reversible aldol-type deavage reactions yielding glycine (120) and an aldehyde (Eigure 10.45) [192]. 

Both threonine aldolases were demonstrated to be pyridoxal phosphate-dependent and to be sulfhydryl enzymes. Michaelis constants were calculated to have the values of 69 X 10 M for L-threonine and 4.25 X 10 M for L-allothreonine. 

The metabolism of j5-hydroxy-a-amino acids involves pyridoxal phosphate-dependent enzymes, classified as serine hydroxymethyltransferase or threonine aldolases, that catalyze reversible aldol-type cleavage to aldehydes and glycine (134) [284]. 

Metabolism of P-hydroxy-a-amino acids involves pyridoxal phosphate-dependent enzymes that catalyze a reversible cleavage to aldehydes (Fig, 31) and glycine (89). The distinction between L-threonine aldolase (ThrA EC 4.1.2.5), L-a//o-threonine aldolase (EC 4.1.2.6), or serine hydroxymethyltransferase (SHMT EC 2.1,2.1) has often been rather vague since many catalysts display only poor capacity for erythro/threo (i.e., 91/90) discrimination [22]. Many enzymes display a broad substrate tolerance for the aldehyde acceptor, notably including variously substituted aliphatic as well as aromatic aldehydes (Fig. 31) however, a,P-unsaturated aldehydes are not accepted. 

The product of the PNP enzyme, FDRP 9 has been purified and characterised. The evidence suggests that FDRP 9 is then isomerised to 5-fluoro-5-deoxyribulose-1-phosphate 10, acted upon by an isomerase (Scheme 7). Such ribulose phosphates are well-known products of aldolases and a reverse aldol reaction will clearly generate fluoroacetaldehyde 11. Fluoroacetaldehyde 11 is then converted after oxidation to FAc 1. We have also shown that there is a pyridoxal phosphate (PLP)-dependent enzyme which converts fluoroacetaldehyde 11 and L-threonine 12 to 4-FT 2 and acetaldehyde in a transaldol reaction as shown in Scheme 8. Thus, all of the biosynthetic steps from fluoride ion to FAc 1 and 4-FT 2 can be rationalised as illustrated in Scheme 7. 

The glycine-dependent aldolases contain a cofactor pyridoxal phosphate (PLP). Binding of glycine to it as an imine enables the deprotonation necessary for the carbon-carbon bond forming reaction, with pyridine acting as an electron sink. The subsequent 100% atom efficient reaction with an aldehyde establishes the new bond and two new stereocenters (Scheme 5.30). Of all the glycine-dependent aldolases only L-threonine aldolase (LTA) is commonly used [40, 43, 52]. 

The glycine-dependent aldolases are pyridoxal 5-phosphate dependent enzymes that catalyze the reversible aldol reaction, where glycine and an acceptor aldehyde form a (i-hydroxy-a-amino acid (Scheme 5.47).74 Serine hydroxymethyltransferases, SHMT (EC 2.1.2.1), and threonine aldolases, two types of glycine dependent aldolases, have been isolated. In... 

Threonine aldolases (ThrA EC4.1.2.5) and serine hydroxymethyltransferases (SHMT EC 2.1.2.1) are pyridoxal-5 -phosphate (PEP) dependent aldolases that catalyze the aldol addition of glydne to aldehydes [155-158], Since two new stereogenic centers are formed, four possible stereoisomers can be formally obtained. However, contrary to the case of DHAP-dependent aldolases, the four set of stereocomplementary enzymes have not been found in nature yet (Scheme 10.7) [157,159,160]. 

The pyridoxal-5 -phosphate-dependent threonine aldolases (ThrA EC 4.1.2.5) and serine hydroxymethyltransferase (SHMT EC 2.1.2.1) catalyze the aldol addition of glycine to aldehydes with the formation of two new stereogenic centers [15,44,161-163]. Hence, four possible products can be formally obtained from a single aldehyde, depending on the specificity of the threonine aldolase. All glycine aldolases assayed... 

Glycine-Dependent Aldolases (ThrA) The group of the glycine-dependent aldolases affords the synthesis of (S-hydroxy-a-amino-acids, d- and L-threonine and serine, most of them are known as L-threonine aldolases (ThrA). They catalyzed the addition of glycine 31 to various aldehyde substrates with pyridoxal-5 -phosphate (PLP) as cofactor. The formed products contain two stereogenic centers whose stereochemistry is controlled by the choice of D- or L-threonine and corresponding d- or L-a//o-threo-nine aldolases (Scheme 28.16). 

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