Histidine deaminase

Nuclear relaxation studies of substrates and inhibitors have resulted in the detection of 10 enzyme-Mur-substrate and 4 enzyme-Mn-inhibitor bridge complexes possessing kinetic and thermodynamic properties consistent with their participation in enzyme catalysis. Three cases of a activation, by divalent cations, of enzyme-catalyzed enolization reactions (pyruvate carboxylase, yeast aldolase, v-xylose isomerase), and one case of 8 activation of an enzyme-catalyzed elimination reaction (histidine deaminase) have thereby been established, Thus, in each proven case, the enzyme-bound Mn coordinates an electronegative atom (Z) of the substrate, which is attached to a carbon atom one or two bonds away from the carbon atom which is to be deprotonated ... 

Histidine deaminase-Mn-imidazole Histidine deaminase-Mn-urocanate... 

An example of 8 activation has been established by the NMR method in the metal-activated histidine deaminase reaction (39). 

Figure 6. Mechanism of the histidine deaminase reaction (from Ref, 39 and 41)...

Another role of the Mn in histidine deaminase may be to mask the nucleophihc imidazole of the substrate to prevent its attacking the electrophilic center of the enzyme. 

In mammals, histidine is an essential amino acid. Consequently, any inborn error leading to histidine accumulation in the blood is likely to result from an alteration in the breakdown pathway. The breakdown pathway of histidine starts with an enzyme called histi-dase, a histidine deaminase. The enzyme in liver catalyzes the conversion of the histidine to urocanic acid. The requirements of the purified liver enzymes are not clear. Although the rabbit enzyme requires folic acid, a divalent cation, and glutathione for activity, the guinea pig enzyme requires only the metal and the SH group. 

The system has been reviewed by Erkama and Virtanen. A similar reaction (discussed in the chapter. Carbon Catabolism of Amino Acids) is carried out by histidine deaminase to yield urocanic acid. 

The Japanese investigators " - proposed an alternate pathway, namely, that histidine was first deaminated to urocanic acid by an enzyme named by them histidine deaminase, and the urocanic acid, in... 

The enzyme which deaminates histidine to form urocanic acid has been called histidase, desaminohistidase, histidine deaminase, histidine-aenzyme preparation which degraded histidine to a product in which the imidazole ring had been split. This process is now known to consist of several steps. The name histidase was adopted by Mehler and Tabor 248) for the enzyme which converts histidine to urocanic acid and ammonia. Histidine deaminase, as a name, has the advantage of identifying the nature of the reaction. 

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