Pyridoxal-5 ’-phosphate -dependent enzymes

FIGURE 14.22 Glutamate aspartate aminotransferase, an enzyme conforming to a double-displacement bisnbstrate mechanism. Glutamate aspartate aminotransferase is a pyridoxal phosphate-dependent enzyme. The pyridoxal serves as the —NH, acceptor from glntamate to form pyridoxamine. Pyridoxamine is then the amino donor to oxaloacetate to form asparate and regenerate the pyridoxal coenzyme form. (The pyridoxamine enzyme is the E form.)... 

Pyridoxal phosphate-dependent enzymes (Schiff base)... 

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]. 

In addition to a-allenic a-amino acids, the corresponding allenic derivatives of y-aminobutyric acid (GABA) have also been synthesized as potential inhibitors of the pyridoxal phosphate-dependent enzyme GABA-aminotransferase (Scheme 18.49) [131,138-142]. The synthesis of y-allenyl-GABA (152) and its methylated derivatives was accomplished through Crabbe reaction [131], aza-Cope rearrangement [138] and lactam allenylation [139], whereas the fluoroallene 153 was prepared by SN2 -reduc-tion of a propargylic chloride [141]. 

This pyridoxal phosphate-dependent enzyme [EC 2.6.1.43] catalyzes the reversible reaction of 5-amino-levulinate with pyruvate to produce 4,5-dioxopentanoate and alanine. 

This enzyme [EC 2.6.1.42], also referred to as transaminase B, catalyzes the reversible reaction of leucine with a-ketoglutarate (or, 2-oxoglutarate) to produce 4-methyl-2-oxopentanoate and glutamate. The pyridoxal-phosphate-dependent enzyme will also utilize isoleucine and valine as substrates. However, this enzyme is distinct from that of valine pyruvate aminotransferase [EC 2.6.1.66]. See also Leucine Aminotransferase... 

This pyridoxal-phosphate-dependent enzyme [EC 4.4.1.8], also referred to as /3-cystathionase and cystine lyase, catalyzes the hydrolysis of cystathionine to yield homocysteine, pyruvate, and ammonia. 

This pyridoxal-phosphate-dependent enzyme [EC 4.4.1.13] catalyzes the conversion of an 5-substituted cysteine (that is, RS-CH2-CH(NH3")C00 ) to RSH, ammonia, and pyruvate. See also S-Substituted Cysteine Sulfoxide Lyase... 

This pyridoxal-phosphate-dependent enzyme [EC 4.2.1.22] (also known as serine sulfhydrase, /3-thionase, and methylcysteine synthase) catalyzes the reaction of homocysteine with serine to produce cystathionine and water. 

This pyridoxal-phosphate-dependent enzyme [EC 4.4.1.10] catalyzes the reaction cysteine with sulfite to produce cysteate and H2S. The enzyme can also catalyze the reaction of two cysteines (thereby producing lanthio-nine) as well as other alkyl thiols as substrates. 

This pyridoxal-phosphate-dependent enzyme [EC 4.1.1.15] catalyzes the conversion of L-glutamate to 4-aminobutanoate and carbon dioxide. The mammalian brain enzyme also acts on L-cysteate, 3-sulfino-L-alanine, and L-aspartate. 

This pyridoxal-phosphate-dependent enzyme [EC 2.1.2.5], also known as glutamate formyltransferase, catalyzes the reaction of 5-formiminotetrahydrofolate with L-glutamate to produce tetrahydrofolate and A-formim-ino-L-glutamate. The enzyme will additionally catalyze the transfer of the formyl moiety from 5-formyltetrahy-drofolate to L-glutamate. This protein occurs in eukaryotes as a bifunctional enzyme also having a formiminote-trahydrofolate cyclodeaminase activity [EC 4.3.1.4]. 

This pyridoxal-phosphate-dependent enzyme [EC 2.6.1.4] catalyzes the reaction of glycine with a-ketoglu-tarate (or, 2-oxoglutarate) to produce glyoxylate and l-glutamate. See also GlycineiOxaloacetate Aminotransferase Glyoxylate Aminotransferase A. E. Braunstein (1973) The Enzymes, 3rd ed., 9, 379. 

This pyridoxal-phosphate-dependent enzyme [EC 3.7.1.3] catalyzes the hydrolysis of kynurenine to produce anthranilate and alanine. 3 -Hydroxykynurenine and some other (3-arylcarbonyl)alanines can also be acted upon by this enzyme. 

This pyridoxal-phosphate-dependent enzyme [EC 2.1.2.1], which has a recommended EC name of glycine hydroxymethyltransferase, catalyzes the reversible reaction of 5,10-methylenetetrahydrofolate with glycine and water to produce tetrahydrofolate and L-serine. The enzyme will also catalyze the reaction of glycine with acetaldehyde to form L-threonine as well as with 4-tri-methylammoniobutanal to form 3-hydioxy-N, N, N -trimethyl-L-lysine. 

This pyridoxal-phosphate-dependent enzyme [EC 4.2.99.9], also known as cystathionine y-synthase, catalyzes the reaction of O-succinyl-L-homoserine with L-cysteine to produce cystathionine and succinate. The enzyme can also use hydrogen sulfide and methanethiol as substrates, producing homocysteine and methionine, respectively. In the absence of a thiol, the enzyme can also catalyze a /3,y-elimination reaction to form 2-oxobu-tanoate, succinate, and ammonia. 

Lactobacillus delbrueckii. In 1953, Rodwell suggested that the histidine decarboxylase of Lactobacillus 30a was not dependent upon pyridoxal phosphate (11). Rodwell based his suggestion upon the fact that the organism lost its ability to decarboxylate ornithine but retained high histidine decarboxylase activity when grown in media deficient in pyridoxine. It was not until 1965 that E. E. Snell and coworkers (12) isolated the enzyme and showed that it was, indeed, free of pyridoxal phosphate. Further advances in characterization of the enzyme were made by Riley and Snell (13) and Recsei and Snell (14) who demonstrated the existence of a pyruvoyl residue and the participation of the pyruvoyl residue in histidine catalysis by forming a Schiff base intermediate in a manner similar to pyridoxal phosphate dependent enzymes. Recent studies by Hackert et al. (15) established the subunit structure of the enzyme which is similar to the subunit structure of a pyruvoyl decarboxylase of a Micrococcus species (16). 

Tiburzy (22,31) obtained similar results by application of the PAL inhibitor aminooxyacetic acid (AOA). However, AOA does not specifically inhibit PAL (99), and PAL is not only involved in lignin biosynthesis (100). Thus, AOA and the related inhibitor aminooxyphenyl propionic acid (AOPP) (101,102) inhibit the biosynthesis of lignin (103,104), anthocyanins (105), other flavonoids (106), and conjugates of cinnamic acids (107) via PAL, as well as ethylene (108-110) via a pyridoxal phosphate dependent enzyme (110,111). In view of the possible function of phenolic compounds as phytoalexins (21,112,113) and the well documented role of ethylene in some resistance reactions (114-116), the above cited experiments with AOA (22,... 

Figure 7.47 Inhibition of pyridoxal phosphate-dependent enzymes by a fluorinated amino acid.

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