Transamination of Amino Acids Aminotransferase Reactions

Hydrolysis of the a-carbon-amino bond of the ketimine results in the release of the oxo-acid corresponding to the amino acid substrate, leaving pyridoxamine phosphate at the catalytic site of the enzyme. In this case, there is no reformation of the internal Schiff base to the reactive lysine residue. This is the half-reaction of transamination. The process is completed by reaction of pyridoxamine phosphate with a second oxo-acid substrate, forming an intermediate ketimine, then by the reverse of the reaction sequence shown in Figure 9.2, releasing the amino acid corresponding to this second substrate after displacement from the aldimine by the reactive lysine residue to reform the internal Schiff base. Transamination is thus a bisubstrate ping-pong reaction, with the amino acid substrate binding to the pyridoxal phosphate form of the enzyme and the oxo-acid substrate to the pyridoxamine phosphate form (as shown in Figure 9.3).

Table 9.3 Transamination Products of the Amino Acids

Amino Acid Oxo-acid





Aspartic acid




Glutamic acid



a-Oxoglutaramic acid










a-Oxo-e-aminocaproate ^ pipecolic acid


S-methyl-ß-thiol 1 a-oxopropionate


Glutamic-7 -semialdehyde















a Lysine does not usually undergo transamination; if it does, the product, a-oxo-e-aminocaproate, undergoes spontaneous dehydration and cyclization to pipecolic acid.

Transamination is of central importance in amino acid metabolism, provid-ingpathwaysforthe catabolism of all amino acids other than lysine (which does not undergo transamination), although pathways other than transamination maybe more important for the catabolism of some amino acids. It also provides a pathway for the synthesis of those amino acids for which there is an alternative source of the oxo-acid (the nonessential amino acids). As can be seen from Table 9.3, many of the oxo-acids are common metabolic intermediates.

Many of the transaminase reactions are linked to the amination of 2-oxo-glutarate to glutamate or glyoxylate to glycine, which are substrates for oxida-tive deamination, reforming the oxo-acids, and thus providing a pathway for net deamination of most amino acids. Steps in the Transaminase Reaction Purified aspartate aminotransferase is capable of catalyzing the half-reaction of transamination (very slowly) in the crystal. This means that the conformational changes that occur during the reaction can be followed by X-ray diffraction crystallography.

The first stage in the reaction is a noncovalent (Michaelis-type) binding of the substrate to the enzyme. The substrate amino acid then attacks the internal Schiff base aldimine nucleophilically at the C=N bond. To acquire nucleophilicity, the substrate must be deprotonated; this is the role of the phenolic -OH group of the coenzyme, which will be partially ionized, and therefore carry some negative charge, when protein bound. This group then forms a dative bond to the imino nitrogen of the internal aldimine, increasing its electrophilicity and thus enhancing the nucleophilic attack by the substrate.

Once the substrate-coenzyme aldimine has been formed, it loses a proton from the a-carbon. The base that catalyzes this is the e- amino group of the lysine residue that was involved in the internal aldimine. At this stage, the attachment of the coenzyme to the enzyme, through the ring nitrogen, the 2 -methyl group and the 5-phosphate group, is especially important in maintaining a rigid geometry as the cofactor ring rotates about its C-2 to C-5 axis to bring the reacting region of the Schiff base into juxtaposition with the various groups at the catalytic site that catalyze the successive stages of the reaction.

The deprotonated aldimine is reprotonated at carbon-4 by reaction with a histamine residue to form the pyridoxamine phosphate ketimine. Hydrolysis of this complex yields the free oxoacid (oxaloacetate), leaving pyridoxamine phosphate at the catalytic site (Ivanov and Karpeisky, 1969). Transamination Reactions of Other Pyridoxal Phosphate Enzymes In addition to their main reactions, anumberofpyridoxalphosphate-dependent enzymes also catalyze the half-reaction of transamination. Such enzymes include serine hydroxymethyltransferase (Section, several decarboxylases, and kynureninase (Section

The result of this half-transaminase reaction is formation of pyridoxamine phosphate at the active site of the enzyme, and hence loss of activity. Pyridoxamine phosphate dissociates from the active site, so that if adequate pyridoxal phosphate is available the resultant apoenzyme can be reactivated.

The ratio of transamination:decarboxylation is relatively small - of the order of 1:10,000 for glutamate decarboxylase. Nevertheless, this is sufficient to result in significant loss of active enzyme, andMeister (1990) suggested that this may be a control mechanism rather than simply a lack of reaction specificity. Transamination and Oxidative Deamination Catalyzed by Di-hydroxyphenylalanine (DOPA) Decarboxylase DOPA decarboxylase catalyzes the decarboxylation of dihydroxyphenylalanine to yield dopamine (and hence the other catecholamine neurotransmitters; see Figure 13.4) and

5-hydroxytryptophan to yield serotonin (5-hydroxytryptamine). Early studies suggested that it was especially susceptible to self-inactivation as a result of catalyzing the half-reaction of transamination (Section However, it only catalyzes half-transamination under anaerobic conditions (commonly used in vitro because of the ready polymerization of DOPA and dopamine to yield melanin in the presence of oxygen). Under aerobic conditions, the enzyme does not seem to catalyze half-transamination, but it does catalyze oxidative deamination of its aromatic amine products (Bertoldi and Borri Voltattorni, 2000, 2001). Side-Chain Elimination and Replacement Reactions The third bond in the Schiff base aldimine that can be labilized by the electron-withdrawing effect of the ring nitrogen is that between the a-carbon and the side chain of the amino acid, resulting in a variety of a, f-elimination and ^-replacement reactions, such as the reactions of serine dehydratase; serine hydroxymethyl-transferase (Section; cysteine lyase, which cleaves cysteine to form alanine and H2S; selenocysteine lyase, which cleaves selenocysteine to release H2Se and alanine; and cystathionine f -synthetase (see Figure 10.9). The reaction may also involve f, y-elimination, as in y-cystathionase (see Figure 10.9).

Cystathionine f -synthetase contains heme as well as pyridoxal phosphate, but this seems to have a regulatory rather than catalytic role; the yeast enzyme does not contain heme (Jhee et al., 2000; Kabil et al., 2001). A common genetic polymorphism in human cystathionine f -synthetase (a 68-base-pair insertion, occurring in about 12% of the general population) is associated with a lower than normal increase in plasma homocysteine after a methionine load in patients with low vitamin B6 status, suggesting that the variant enzyme may have higher affinity for its cofactor than the normal form - the reverse of the position in the vitamin B6 responsive genetic diseases discussed in Section 9.4.3 (Tsaietal., 1999).

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  • ruben mcmillan
    Why cant cysteine undergo transamination?
    1 year ago
    Why does lysine and threonine not undergoes transamination?
    1 year ago
  • Matilda
    Why lysine does not undergo transamination?
    1 year ago
  • faramir goodbody
    Why can't lysine be transaminated?
    8 months ago
  • adiam
    Why is lysine not involved in tansamination reactions?
    7 months ago
  • mewael
    Why cant threonine undergo transamination?
    4 months ago
  • belba
    What are the transamination enzymes?
    4 months ago
  • kristian
    Is serine to glycine a transamination reaction?
    4 months ago
  • meaza
    Can pyruvate undergo transamination with any amino acid?
    2 months ago
    Can histidine undergo transamination?
    2 months ago

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