Pyridoxal transaminase

Amino acids NAD(P)H Pyridoxamine 5 -phosphate Pyruvate Amines Pyridoxal 5-phosphate dependent enzymes Dehydrogenases Transaminases Pyridoxal 5-phosphate dependent enzymes Amino acid decarboxylases... 

GABA transaminase is a mitochondrial enzyme which, like GAD, requires pyridoxal phosphate as co-factor. It is present in both neurons and glia and while secondary to... 

A few years later, in 1953, the versatility of pyridoxal phosphate was illustrated by Snell and his collaborators who found many of the enzyme reactions in which pyridoxal phosphate is a coenzyme could be catalyzed non-enzymically if the substrates were gently heated with pyridoxal phosphate (or free pydridoxal) in the presence of di- or tri-valent metal ions, including Cu2+, Fe3+, and Al3+. Most transaminases however are not metal proteins and a rather different complex is formed in the presence of the apoprotein. 

Pyridoxine (B ) Pyridoxal-P (PLP) Aminotransferases (transaminase) AST (GOT), ALT (GPT) 8-Aminolevulinate synthase Protein catabolism Heme synthesis MCC isoniazid therapy Sideroblastic anemia Cheilosis or stomatitis (cracking or scaling of lip borders and corners of the mouth) Convulsions... 

Baltzer and co-workers have utilized a synthetic peptide scaffold to incorporate features of transaminase enzymes [ 13]. Using this approach, they have attempted to achieve the selective and tight binding of a pyridoxal phosphate coenzyme observed in transaminase enzymes. A synthetic helix-turn-helix peptide known to dimerize into a four-helix bundle was chosen as the platform for design [5]. 

Glutamate can then participate in the formation of other amino acids via the process called transamination. Transamination is the exchange of the amino group from an amino acid to a keto acid, and provides the most common process for the introduction of nitrogen into amino acids, and for the removal of nitrogen from them. The reaction is catalysed by a transaminase enzyme, and the coenzyme pyridoxal phosphate (PLP) is required. 

Among the NH2 transfer reactions, transaminations (1) are particularly important. They are catalyzed by transaminases, and occur in both catabolic and anabolic amino acid metabolism. During transamination, the amino group of an amino acid (amino acid 1) is transferred to a 2-oxoacid (oxoacid 2). From the amino acid, this produces a 2-oxo-acid (a), while from the original oxoacid, an amino acid is formed (b). The NH2 group is temporarily taken over by enzyme-bound pyridoxal phosphate (PLP see p. 106), which thus becomes pyridoxamine phosphate. 

In the absence of substrates, the aldehyde group of pyridoxal phosphate is covalently bound to a lysine residue of the transaminase (1). This type of compound is known as an aldimine or Schiffs base. During the reaction, amino acid 1 (A, la) displaces the lysine residue, and a new aldimine is formed (2). The double bond is then shifted by isomerization. 

This enzyme [EC 2.6.1.2], also known as glutamic-pyruvic transaminase and glutamic-alanine transaminase, catalyzes the pyridoxal-phosphate-dependent reaction of alanine with 2-ketoglutarate, resulting on the production of pyruvate and glutamate. 2-Aminobutanoate will also react, albeit slowly. There is another alanine aminotransferase [EC 2.6.1.12], better known as alanine-oxo-acid aminotransferase, which catalyzes the pyridoxal-phosphate-dependent reaction of alanine and a 2-keto acid to generate pyruvate and an amino acid. See also Alanine Glyoxylate Aminotransferase... 

This enzyme [EC 2.6.1.21], also known as D-aspartate aminotransferase, D-amino acid aminotransferase, and D-amino acid transaminase, catalyzes the reversible pyridoxal-phosphate-dependent reaction of D-alanine with a-ketoglutarate to yield pyruvate and D-glutamate. The enzyme will also utilize as substrates the D-stereoisomers of leucine, aspartate, glutamate, aminobutyrate, norva-hne, and asparagine. See o-Amino Acid Aminotransferase... 

This enzyme [EC 2.6.1.1] (also known as transaminase A, glutamicioxaloacetic transaminase, and glutamic aspartic transaminase) catalyzes the reversible reaction of aspartate with a-ketoglutarate to produce oxaloace-tate and glutamate. Pyridoxal phosphate is a required cofactor. The enzyme has a relatively broad specificity, and tyrosine, phenylalanine, and tryptophan can all serve as substrates. 

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... 

Among the numerous enzymes that utilize pyridoxal phosphate (PLP) as cofactor, the amino acid racemases, amino acid decarboxylases (e.g., aromatic amino acids, ornithine, glutamic acid), aminotransferases (y-aminobutyrate transaminase), and a-oxamine synthases, have been the main targets in the search for fluorinated mechanism-based inhibitors. Pharmaceutical companies have played a very active role in this promising research (control of the metabolism of amino acids and neuroamines is very important at the physiological level). 

Canaline reacts with the pyridoxal phosphate moiety of enzymes possessing this vitamin Bg-containing decarboxylases and transaminases typically are inhibited strongly by this non-protein amino acid (, ). When canaline reacts with free pyridoxal... 

Vitamin B6 occurs naturally in three related forms pyridoxine (6.26 the alcohol form), pyridoxal (6.27 aldehyde) and pyridoxamine (6.28 amine). All are structurally related to pyridine. The active co-enzyme form of this vitamin is pyridoxal phosphate (PLP 6.29), which is a co-factor for transaminases which catalyse the transfer of amino groups (6.29). PLP is also important for amino acid decarboxylases and functions in the metabolism of glycogen and the synthesis of sphingolipids in the nervous system. In addition, PLP is involved in the formation of niacin from tryptophan (section 6.3.3) and in the initial synthesis of haem. 

Hydrazines may be nucleophiles such as when they interact with aldehyde and keto groups to form hydrazones. This is the basis for the inhibition of enzymes such as transaminases, which rely on pyridoxal phosphate as a coenzyme. Mono-substituted hydrazines can be formed as metabolites when azo groups are reduced, dialkylated hydrazines are dealkylated or hydrazides are hydrolysed. 

Terms in bold are defined in aminotransferases 660 transaminases 660 transamination 660 pyridoxal phosphate (PLP) 660 oxidative deamination 661 l-glutamate dehydrogenase 661 glutamine synthetase 662 glutaminase 663 creatine kinase 664... 

Mechanisms of action of pyridoxal phosphate (a) in glutamate-oxaloacetate transaminase, and (b) in aspartate /3-decarboxylase. 

Pyridoxine, pyridoxal, and pyridoxamine, which occur in foodstuffs, are collectively known as vitamin Bg. In the body, all three are converted to pyridoxal phosphate which is the coenzyme for amino-acid decarboxylase and for transaminase. The structures of the three active forms of vitamin Bg and the pyridoxal phosphate, are shown below (55). 

The a-amino groups are removed from amino acids by a process called transamination. The acceptor for this reaction is usually the a-keto acid called a-ketoglutarate which results in the formation of glutamate and the corresponding a-keto acid. The coenzyme of all transaminases is pyridoxal phosphate which is derived from vitamin B6 and which is transiently converted during transamination into pyridoxamine phosphate. 

The reactions catalyzed by transaminases are anergonic as they do not require an input of metabolic energy. They are also freely reversible, the direction of the reaction being determined by the relative concentrations of the amino acid-keto acid pairs. Pyridoxal phosphate is not just used as the coenzyme in transamination reactions, but is also the coenzyme for several other reactions involving amino acids including decarboxylations, deaminations, racemizations and aldol cleavages. 

One of the earliest published attempts to create antibodies with catalytic activity had as its goal the generation of a transaminase. Raso and Stollar prepared V-(5-phosphopyridoxyl)-3 -amino-L-tyrosine 154 as a mimic of the Schiff s base intermediate that is formed during the pyridoxal-dependent transamination of tyrosine and showed that it was a site-directed inhibitor of the enzymes tyrosine transaminase and tyrosine decarboxylase.132 Partially purified polyclonal antibodies, elicited against y-globulin conjugates of the hapten, recognized both the... 

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