Purine nitrogen sources

This chemistry seems less probable, however, given the structural similarity of the smPurL proteinand aminoimidazole ribonucleotide (AIR) synthetase (PurM), another enzyme in the purine biosynthetic pathway that is known to form an iminophosphate intermediate (Scheme 16). Under in vitro conditions, FGAR-AT can use ammonia as an alternate nitrogen source when glutamine is absent. 

In 1953, Richer and Westerfeld, and almost simultaneously De Renzo et al. (1953), discovered molybdenum in this enzyme and established a functional role for the trace element in animals. In lower animals, the enzyme serves for the utilization of purine as a nitrogen source, but in higher organisms its true physiological function is not clear. The best-studied reaction of this enzyme is the conversion of xanthine into uric acid under the action of xanthine dehydrogenase (XDH) (Table 18.8) ... 

Fig. U Comparison on basis of the purine nitrogen content Correlation between purine nitrogen load [from purines in different sources as in 5 -AMP, 5 -GMP, RNA and DNA] and plasma levels of uric acid...

Figure 34-1. Sources of the nitrogen and carbon atoms of the purine ring. Atoms 4,5, and 7 (shaded) derive from glycine.

A novel approach to purine synthesis involves the use of ADC compounds as a source of one nitrogen atom in the five-membered ring.148 150 Treatment of 6-amino-l,3-dimethyluracil (94, R = H) with DEAZD gives the 5-substitution product (95, R = H). The N—N bond is cleaved by Raney nickel or formic acid, and ring closure to 1,3-dimethyluric acid is simply effected by heating.148 Whether the initial adduct is formed by a substitution... 

The two classes of nucleotide that must be synthesised are the pyrimidine and purine ribonucleotides for RNA synthesis and the deoxyribonucleotides for DNA synthesis. For the original sources of the nitrogen atoms in the bases of the pyrimidine and purine nucleotides, see Figure 20.7. The pathway for the synthesis of the pyrimidine nucleotides is... 

Figure 20.7 Sources of carbon and nitrogen atoms in pyrimidine and purine bases. The dotted lines represent the bonds between the atoms. The shaded areas represent atoms or groups of atoms from precursor molecules.

Discussing the biosynthetic pathways for amino acids and nucleotides together is a sound approach, not only because both classes of molecules contain nitrogen (which arises from common biological sources) but because the two sets of pathways are extensively intertwined, with several key intermediates in common. Certain amino acids or parts of amino acids are incorporated into the structure of purines and pyrimidines, and in one case part of a purine ring is incorporated into an amino acid (histidine). The two sets of pathways also share... 

The imidazole ring of histidine (30) arises by a quite different route to that used for the formation of the imidazole ring in purine biosynthesis. The sources of the carbon and nitrogen atoms of histidine were established as a result of a series of labelling experiments with T4C and 15N substrates coupled with degradation of the labelled histidines. A summary of these results is given in Scheme 7 (59JBQ234)586). 

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