Current concepts on the regulation of purine biosynthesis de novo in man

In the present discussion we have presented our views on how purine biosynthesis de novo is regulated in man. The rate of the initital step unique to purine ribonucleotide biosynthesis de novo is controlled by the intracellular concentration of PP-ribose-P and purine ribonucleotides. This critical interaction of PP-ribose-P and purine ribonucleotides may be explained by a change in the physical properties of the enzyme that catalyzes this reaction. The first branch point in the pathway, following this initial step involves the utilization of IMP. Based on an in vitro analysis of the enzymes participating directly in the two biosynthetic pathways for which IMP is a substrate, we propose that the intracellular level of GTP may be more critical than previously recognized.