Pyridoxal-5 -phosphate enzymes

Walsh C, RA Pascal, M Johnston, R Raines, D Dikshit, A Krantz, M Houma (1981) Mechanistic studies on the pyridoxal phosphate enzyme 1-aminocyclopropane-l-carboxylate deaminase from Pseudomonas sp. Biochemistry 20 7509-7519. 

Inhibition of pyridoxal phosphate enzymes by fluoroalanines has been widely studied. Among the numerous examples, alanine racemase, tyrosine phenol... 

Klrsch, J.F. Eliot, A.C. (2004) Pyridoxal phosphate enzymes mechanistic, structural and evolutionary considerations. Annu. 

This book includes excellent accounts of reaction mechanisms, including one-carbon metabolism and pyridoxal phosphate enzymes. 

Pyridoxal phosphate enzymes mediate the nonoxidative decarboxylation of amino acids. This mechanism is of primary importance in bacteria, but it may be essential to proper function of the nervous system in humans... 

Would you expect phosphatidylserine decarboxylase (fig. 19.3) to be a pyridoxal phosphate enzyme ... 

Other classes of enzyme included in Table 5 are the pyridoxal phosphate enzymes and those associated with vitamin B12. 

The chromophoric pyridoxal phosphate coenzyme provides a useful spectrophotometric probe of catalytic events and of conformational changes that occur at the pyridoxal phosphate site of the P subunit and of the aiPi complex. Tryptophan synthase belongs to a class of pyridoxal phosphate enzymes that catalyze /3-replacement and / -elimination reactions.3 The reactions proceed through a series of pyridoxal phosphate-substrate intermediates (Fig. 7.6) that have characteristic spectral properties. Steady-state and rapid kinetic studies of the P subunit and of the aiPi complex in solution have demonstrated the formation and disappearance of these intermediates.73-90 Fig. 7.7 illustrates the use of rapid-scanning stopped-flow UV-visible spectroscopy to investigate the effects of single amino acid substitutions in the a subunit on the rate of reactions of L-serine at the active site of the P subunit.89 Formation of enzyme-substrate intermediates has also been observed with the 012P2 complex in the crystalline state.91 ... 

Common stereochemical features of pyridoxal phosphate enzymes... 

Transamination Reactions of Other Pyridoxal Phosphate Enzymes Inaddition to theirmainreactions, anumberofpyridoxalphosphate-dependent enzymes also catalyze the half-reaction of transamination. Such enzymes include serine hydroxymethyltransferase (Section 10.3.1.1), several decarboxylases, and kynureninase (Section 8.3.3.2). 

Jhee KH, McPhie P, and Miles EW (2000) Yeast cystathionine beta-synthase is a pyridoxal phosphate enzyme but, unlike the human enzyme, is not a heme protein. Journal of Biological Chemistry 275,11541. ... 

Figure 23.12. Bond Cleavage by PLP Enzymes. Pyridoxal phosphate enzymes lahilize one of three bonds at the a-carhon atom of an amino acid substrate. For example, bond a is labilized by aminotransferases, bond b by decarboxylases, and bond c by aldolases (such as threonine aldolases). PLP enzymes also catalyze reactions at the ()- and y-carbon atoms of amino acids. 

Figure 23.13. Stereoelectronic Effects. The orientation about the NH-Ca bond determines the most favored reaction catalyzed by a pyridoxal phosphate enzyme. The bond that is most nearly perpendicular to the 7i orbitals of the pyridoxal phosphate electron sink is most easily cleaved.

Quite recently Weber and Wiss (W8) studied the influence of vitamin Be depletion on various pyridoxal phosphate enzymes and found that rat liver kynureninase is much more affected by vitamin Be deficiency than kynurenine transaminase. In fact liver kynureninase of rats on a Be-deficient diet fell to 17%, whereas kynurenine transaminase was about 58% of the original activity after the same period. The different behavior of these two enzymes offers a way of studying closely the mechanism of the increased excretion of xanthurenic acid in pyridoxine... 

Pyridoxal Phosphate Enzymes Catalyze a Wide Array of Reactions... 

Our laboratory has studied the stereochemistry of methyl group formation in a number of a, 0 elimination reactions of amino acids catalyzed by pyridoxal phosphate enzymes. The reactions include the conversions of L-serine to pyruvate with tryptophan synthase 02 protein (78) and tryptophanase (79), of L-serine and l-tyrosine with tyrosine phenol-lyase (80), and l-cystine with S-alkylcysteine lyase (81). In the latter study, the stereospecific isotopically labeled L-cystines were obtained enzymatically by incubation of L-serines appropriately labeled in the 3-position with the enzyme O-acetyl serine sulfhy-drase (82). The serines tritiated in the 3-position were prepared enzymatically starting from [l-3H]glucose and [l-3H]mannose by a sequence of reactions of known stereochemistry (81). The cysteines were then incubated with 5-alkyl-cysteine lyase in 2H20 as outlined in Scheme 19. The pyruvate was trapped as lactate, which was oxidized with K2Cr202 to acetate for analysis. Similarly, Cheung and Walsh (71) examined the conversion of D-serine to pyruvate with... 

E. W. Miles, Pyridoxal phosphate enzymes catalyzing fl-elimination and 3-replacement reactions, in Pyridoxal Phosphate and Derivatives, Vol. I in the series Coenzymes and Cofactors, (eds. D. Dolphin, R. Poulson, and O. Avramovic), John Wiley and Sons, New York, 1986, pp. 253-310. 

The Schiff s base formation between AdoMet and the pyridoxal phosphate-enzyme complex leads to elimination of a proton at a-C of AdoMet to generate a carbanion. The positive sulfonium ion of AdoMet activates the methylene at 7-C and facilitates the intramolecular y-displacement reaction by the carbanion, generating ACC and MTA. The direct 7-displacement was demonstrated by Ramalingam et al. [78]. 

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