PURINE BIOSYNTHESIS

Purines are biologically synthesized as nucleotides and in particular as ribotides, i.e. bases attached to ribose- 5-phosphate. Purines are synthesized by two types of pathways, the de novo pathways and the salvage pathways. De novo synthesis of purines begins with the metabolic precursors like amino acids, ribose-5-phosphate, CO2 and NH3. Salvage pathways recycle the free bases and nucleosides released from nucleic acid breakdown. The purine ring structure is first built up to one or few atoms and then attached to ribose sugar to form nucleotides.

Amino acid glycine is an important precursor in purine synthesis, aspartate is also used as source of amino group. The enzymes for de novo synthesis are present as large, multienzyme complexes in the cell. The two parent purine nucleotides are adenosine monophosphate (AMP; adenylate) and guanosine monophosphate (GMP; guanylate) A key regulatory step is the production of 5- phosphoribosyl-1-pyrophosphate (PRPP) by PRPP synthetase.

DE NOVO SYNTHESIS OF PURINES ENZYMES USED

ENZYMES USED

Biosynthesis of AMP and GMP from IMP

Regulation of purine biosynthesis

Salvage pathway for purine biosynthesis Purines from nucleic acids or from food can also be salvaged and reused in new nucleotides. The brain is especially dependent on the salvage pathway . The enzyme adenine phosphoribosyltransferase (APRT) salvages adenine. The enzyme hypoxanthine-guanine phosphoribosyltranferase (HGPRT) salvages hypoxanthine and guanine. Genetic deficiency of HGPRT leads to Lesch-Nyhan Syndrome in male children. Adenine + PRPP  AMP + PPi