Transamination nonenzymic

Fig. 10. Attempted nonenzymic transaminations of arsonoalanine and phosphono-alanine. Pathway 1 shows the arsenite elimination by arsonoalanine. Pathway 2 shows...

Other reactions that mimic the enzymic processes that require pyridoxal phosphate also have been realized. Werle and Koch reported the nonenzymic decarboxylation of histine (9). The racemization of alanine occurs in preference to its transamination when aqueous solutions with polyvalent cations are maintained at pH 9.5. Other amino acids are likewise racemized the order of rates is Phe, Met > Ala > Val > lieu. At lower pH, the dominant reaction is transamination, with pH maxima varying from 4.3-8 with the nature of the metal ion used as catalyst. 

The ring nitrogen of pyridoxal phosphate exerts a strong electron withdrawing effect on the aldimine, and this leads to weakening of all three bonds about the a-carbon of the substrate. In nonenzymic reactions, all the possible pyridoxal-catalyzed reactions are observed - a-decarboxylation, aminotrans-fer, racemization and side-chain elimination, and replacement reactions. By contrast, enzymes show specificity for the reaction pathway followed which bond is cleaved will depend on the orientation of the Schiff base relative to reactive groups of the catalytic site. As discussed in Section 9.3.1.5, reaction specificity is not complete, and a number of decarboxylases also undergo transamination. 

It is not known to what extent taurine may be a dietary essential for human beings. There is little cysteine sulfinic acid decarboxylase activity in the human liver and, like the cat, loading doses of methionine and cysteine do not result in any significant increase in plasma taurine. This may be because cysteine sulfinic acid can also undergo transamination to /3-sulfhydryl pyruvate, which then loses sulfur dioxide nonenzymically to form pyruvate, thus regulating the amount of taurine that is formed from cysteine. There is no evidence of the development of any taurine deficiency disease under normal conditions. 

Imidazolone propionate hydrolase catalyzes the enzymatic cleavage of the imidazole ring to yield formi-minoglutamate. The rat liver enzyme has been partially purified. In addition to the enzymic conversion, two nonenzymic spontaneous reactions yield N-formyl-isoglutamine and 4-oxoglutamic acid. In addition to the oxidative pathways for histidine, there exist three other pathways for its use protein synthesis, decarboxylation to yield histamine (see Inflammation), and transaminase. The activity of histidine pyruvic transamination in rat liver is three times that of histidase. The product of the transaminase reaction is imidazole pyruvic acid, which in turn is converted to imidazole acetic acid. 

The mechanism of reaction of pyridoxine in transamination was elucidated by three groups of studies studies on nonenzymic transamination in the absence of pyridoxine, studies on nonenzymic transamination in the presence of pyridoxine, and studies on enzymic transamination. The studies are briefly reviewed here because they illustrate the continuity of the mechanism regulating organic and biological reactions. Long ago, chemists described reactions that resemble biological transamination. Approximately equimolecular amounts of benzaldehyde CO2 and alanine are formed... 

The role of pyridoxal in the transamination reaction has been extensively investigated by comparing the mechanism of action of nonenzymic transamination (see Fig. 4-28) in the presence of metal (iron) acting as a catalyst to the transamination catalyzed by the specific proteins. The mechanism of the nonenzymic transamination was deduced from a series of rather simple observations (1) when an amino acid is added to a dilute solution of pyridoxal or pyridoxine phosphate, the absorption maximum of the solution shifts from 345 mp to 430 mp. This change in absorption... 

Fig. 4-29. The role of Schiff base in nonenzymic transamination. 1 pyridoxal + amino acid in presence of catalyst (metal or enzyme) yields a Schiff base. 2 Hydrogen and double-bond shifts lead to the formation of an isomeric Schiff base. 2 The base splits and leads to the formation of the keto acid and pyridoxamine. 4 The reaction is reversible. In the reversible step, the amino group of pyridoxamine is transferred to the keto acceptor...

Nonenzymic transamination reactions involving pyridoxal, metal ions. 

Longenecker and Snell (274) have proposed a sequence of reactions shown in Fig. 1 to explain nonenzymic transamination systems involving pyridoxamine and pyridoxal. The same mechanism has been proposed by these authors to account for the above observations in the case of enzymic transamination. In the latter case, the apoenzyme is considered to play the role of the metal (M in Fig. 1). While there have been some reports suggesting the requirement for a metal in enzymic transamination systems (see 273) the evidence to date is inadequate on this point. Until transaminases of very high purity are prepared this will remain a moot point. A further feature of the reaction mechanism proposed by Longenecker and Snell is that an explanation is offered for the observations by Konikova, et al. (289) and Hilton et al. (290,291) on the labilization of the a-hydrogen atom of the substrate amino acid during transamination. 

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