Purine aminohydrolase

The existence of two separate enzymes in animal tissues responsible for the liberation of ammonia from each of the two aminopurines, adenine and guanine, the latter specific for the free purine and the former for the nucleosides, was initially presented by Jones and his colleagues 11, 12). In 1928, Schmidt 13-15) demonstrated that AMP aminohy-drolase was responsible for the appearance of inosinic acid in muscle and for at least a portion of ammonia liberated during contraction. He showed not only a marked specificity for deamination of 5 -AMP but also provided the first clue that muscle adenylic acid (5 -AMP) and yeast adenylic acid (3 -AMP) were different compounds. Initial evidence for guanine and adenosine aminohydrolase including aspects of the specificity were also described by Schmidt 16). Additional details regarding development of interest in purine aminohydrolases are available in several excellent reviews 17-20). 

Purine aminohydrolases may be assayed by measuring release of ammonia (13, 14) or directly by the much more convenient spec-trophotometric method developed by Kalckar (61) and Rousch and Norris (62). Absorbancy changes resulting from enzymic hydrolysis of the purines or purine derivatives are summarized in Table I (62-75). 

Adenine aminohydrolase has been found in micro-organisms, but not in mammalian cells, and the substrate specificities of the enzymes from Azotobacter vinelandii and Candida utilis were found to be similar [55, 56], Among other purines, 2-aminoadenine, A -aminoadenine, and 6-chloropurine were found to be substrates [55]. ... 

Muscular work is accompanied by the production of ammonia, the immediate source of which is adenosine 5 -phosphate (AMP).301 302 This fact led to the recognition of another substrate cycle (Chapter 11) that functions by virtue of the presence of a biosynthetic pathway and of a degradative enzyme in the same cells (cycle A, Fig. 25-17). This purine nucleotide cycle operates in the brain303 304 as well as in muscle. The key enzyme 5-AMP aminohydrolase (AMP deaminase step a, Fig. 25-17) also occurs in erythrocytes and many other tissues.304 305 Persons having normal erythrocyte levels but an absence of this enzyme in muscles suffer from muscular weakness and cramping after exercise.306... 

Calf duodenal adenosine aminohydrolase affects enzymic hydrolysis of a wide variety of 6-substituted purine derivatives as well as analogs of adenosine with alteration in the purine ring and sugar moiety (Table IV) (65, 65a, 67, 70, 71, 112). Although not noted in Table IV, AMP, ADP, and ATP are not substrates. The hydrolysis of the 6-methoxy-purine derivative in H2180 occurs between C-6 and oxygen (113) consistent with the observed back incorporation of 180 from H2180 into inosine as catalyzed by both calf duodenal and Takadiastase non-... 

After purine nucleotides have been converted to the corresponding nucleosides by 5 -nucleotidases and by phosphatases, inosine and guanosine are readily cleaved to the nucleobase and ribose-1-phosphate by the widely distributed purine nucleoside phosphorylase. The corresponding deoxynucleosides yield deoxyribose- 1-phosphate and base with the phosphorylase from most sources. Adenosine and deoxyadenosine are not attacked by the phosphorylase of mammalian tissue, but much AMP is converted to IMP by an aminohydrolase (deaminase), which is very active in muscle and other tissues (fig. 23.20). An inherited deficiency of purine nucleoside phosphorylase is associated with a deficiency in the cellular type of immunity. 

Purine, Purine Nucleoside, Purine Nucleotide Aminohydrolases... 

Purine, Purine Nucleoside, Purine Nucleotide Aminohydrolases C. L. Zielke and C. H. Suelter... 

Purine nucleotide catabolism is outlined in Figure 15.12. There is some variation in the specific pathways used by different organisms or tissues to degrade AMP. In muscle, for example, AMP is initially converted to IMP by AMP deaminase (also referred to as adenylate aminohydrolase). IMP is subsequently hydrolyzed to inosine by 5 -nucleotidase. In most tissues, however, AMP is hydrolyzed by 5 -nucleotidase to form adenosine. Adenosine is then deaminated by adenosine deaminase (also called adenosine aminohydrolase) to form inosine. 

Figure 3. Compartmentalization of the purine salvage pathway of Leishmania. Abbreviations are as follows AAH, adenine aminohydrolase XPRT, xanthine phosphoribosyltransferase HGPRT, hypoxanthine-guaninephosphoribosyltransferase ADSS, adenylosuccinate synthetase ASL, adenylosuccinate lyase IMPDH, inosine monophosphate dehydrogenase GMPS, gua-nosine monophosphate synthase GDA, guanine deaminase AMPDA, adenosine monophosphate deaminase GMPR, guanosine monophosphate reductase APRT, adenine phosphoribosyltransferase AK, adenosine kinase. Enzymes that have been localized are shown in black and those that are predicted to be in the denoted locations are depicted in gray.

---