Biosynthesis of purine nucleotides

Purine nucleotides can be produced by two different pathways. The salvage pathway utilizes free purine bases and converts them to their respective ribonucleotides by appropriate phosphoribosyltransferases. The de novo pathway utilizes glutamine, glycine, aspartate, N -formyl FH4, bicarbonate, and PRPP in the synthesis of inosinic acid (IMP), which is then converted to AMP and GMP. 

Koolman, Color Atlas of Biochemistry, 2nd edition 2005 Thieme All rights reserved. Usage subject to terms and conditions of license. 

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Shaw and co-workers during studies into the de novo biosynthesis of purine nucleotides demonstrated that 4(5)-aminoimidazole (25 R = H) on treatment with a saturated aqueous solution of potassium bicarbonate at 70°C for 15 min gave 4-aminoimidazole-5-carboxylic acid (38) in an estimated yield of 40% [71JCS(C)1501]. This and related reactions are discussed in more detail in Section V,B,4. 

Patients with Lesch-Nyhan syndrome have hyperuricemia, indicating an increased biosynthesis of purine nucleotides, and markedly decreased levels of hypoxanthine phbs-phoribosyl transferase (HPRT). The hyperuricemia can be explained on the basis of a decrease in which regulator of purine biosynthesis ... 

Folic Acid Antagonists. Folic acid antagonists block the biosynthesis of purine nucleotides. Methotrexate (7.76) is the prototypic fohc acid antagonist and functions by binding to the active catalytic site of dihydrofolate reductase, thereby interfering with the synthesis of the reduced form that accepts one-carbon units lack of this cofactor blocks the synthesis of purine nucleotides. As well as being used in the treatment of cancer, methotrexate has been used in the management of rheumatoid arthritis, psoriasis, and even asthma. 

Figure 25-15 Biosynthesis of purine nucleotides from ribose 5 -phosphate.

Biosynthesis of purine nucleotides Chapter Flaks and Lukens B-63MI40902... 

The preparation of purines via an appropriate pyrimidine dominated the synthetic chemistry of purine especially in the early pre Second World War literature. The reason for this is undoubtedly connected with the difficulty of obtaining suitable imidazole, compared with pyrimidine, precursors and additionally by the tendency of imidazole precursors to be rather labile and prone to aerial oxidation. To some extent these disadvantages have been overcome in recent years and this particular route to purines including nucleosides and nucleotides has been used increasingly. The method of course is of special significance in that it is the route adopted in living systems for the de novo biosynthesis of purine nucleotides, and interestingly it also appears to be the route favoured in the so-called abiotic syntheses from simple acyclic precursors (see Section 4.09.8.1). 

The salvage pathway does not involve the formation of new heterocyclic bases but permits variation according to demand of the state of the base (B), i.e. whether at the nucleoside (N), or nucleoside mono- (NMP), di- (NDP) or tri- (NTP) phosphate level. The major enzymes and routes available (Scheme 158) all operate with either ribose or 2-deoxyribose derivatives except for the phosphoribosyl transferases. Several enzymes involved in the biosynthesis of purine nucleotides or in interconversion reactions, e.g. adenosine deaminase, have been assayed using a method which is based on the formation of hydrogen peroxide with xanthine oxidase as a coupling enzyme (81CPB426). 

B34. Buchanan, J. M., Biosynthesis of purine nucleotides. In The Nucleic Acids"... 

See also DNA, Purines, De Novo Biosynthesis of Purine Nucleotides, DNA Replication Overview... 

See also Nucleotides, Guanine, DeNovo Biosynthesis of Purine Nucleotides, G Proteins in Vision... 

IMP is an intermediate in de novo biosynthesis of purine nucleotides (Figure 22.4) and is found in several purine nucleotide metabolic pathways. 

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