Question

When starting with PRPP and other needed materials, describe (in words) the biosynthesis of the purine intermediate AIR. And when starting with SACAIR describe the biosynthesis of the purine GMP. And how are they different?

Answer 1

Synthesis of purines occurs in many parts of the body especially liver. RBC and Brain cannot synthesize purines. Purines are produced as ribonucleotides not as free bases.

Ribose-5-phosphate generated in the HMP Shunt reacts with ATP to form PRPP (Phosphoribosylpyrophosphate). Glutamine reacts with PRPP and donates its amine group to PRPP and remove Inorganic pyrophosphate moeity to give rise to Beta-5- Phosphoribosylamine (PRA) in the presence of enzyme PRPP Glutamyl transferase. PRA combines with Glycine with the help of enzyme GAR Synthetase and utilizes one molecule of ATP to give rise to GAR ( Glycinamide Ribotide) This GAR uses Formyl group of N10 Formyl THF in the presence of enzyme GAR Formyltransferase to give rise to FGAR (Formyl Glycinamide Ribotide). FGAR in the presence of FGAM synthetase utilizes amide group of Glutamine and one molecule of ATP to form Formylglycinamide Ribotide (FGAM). This in turn utilizes one molecule of ATP and forms AIR (Aminoimidazole Ribotide) with enzyme AIR synthetase.

When starting with SACAIR (Aminoimidazole Succinylcarboxamide Ribotide), it first gives rise to AICAR (Aminoimidazole Carboxamide Ribotide) with help of enzyme Adenylosuccinate lyase with liberation of Fumarate. AICAR formyltransferase transfers formyl group of N10 Formyl THF to AICAR to form FAICAR (Formaminoimidazole Carboxamide Ribotide). FAICAR in presence of Hydrolase form IMP (Inosine Monophosphate). IMP generates NADH+H in presence of IMP dehydrogenase to form XMP (Xanthine Monophosphate). XMP utilizes amide group of Glutamine in presence of Transamidinase to form GMP (Guanine Monophosphate).

AIR intermediate is common to both AMP (Adenine Monophosphate) and GMP formation. The reaction is common till the formation of IMP. When amino group of aspartate is linked to IMP and carbon skeleton is removed as fumarate resulting in the formation of AMP. When Glutamine transfers its amide group of XMP using ATP, it leads to formation of GMP.