Human Phosphoribosylpyrophosphate Research Articles

Delineation of Effectors Impact on The Human Brain Derived Phosphoribosylpyrophosphate Synthetase-1 Activity

Phosphoribosylpyrophosphate synthetase-1 [PRPS-1; EC=2.7.6.1) catalyzes the phosphoribosylation of ribose 5...

Human phosphoribosylpyrophosphate (PRPP) synthetase requirements for subunit aggregation.

The high energy sugar phosphate 5-phosphoribosyl 1-pyrophosphate (PRPP) is synthesized from MgATP and ribose-5-phosphate in a reaction catalyzed by PRPP synthetase (E.C. 2.7.6.1). In vitro studies of this enzyme,1–6 as well as evaluations of PRPP production in intact cells, 7,8 indicate that PRPP synthetase activity is regulated in a complex fashion involving the interaction of substrates, activators, reaction products and diverse inhibitors. Enzyme activity is strictly dependent upon the presence of inorganic phosphate (Pi) and Mg2+ which serve both as activators and cofactors.3 Among inhibitors of PRPP synthetase activity are purine, pyrimidine and pyridine nucleotide end-products of the pathways of PRPP utilization, the reaction products (PRPP and AMP), and 2,3-DPG.3,6

Regulation of human amidophosphoribosyltransferase: Interaction of orthophosphate, PP-ribose-P, and purine ribonucleotides

The present report describes the effects of orthophosphate on the kinetic and physical properties of human glutamine phosphoribosylpyrophosphate amidotransferase (amidophosphoribosyltransferase, EC 2.4.2.14). Enzyme activity was shown to be dependent on the concentration of Pi relative to that of PP-ribose-P and purine ribonucleotides. The Hill coefficient for PP-ribose-P decreased from 1.83 ± 0.08 to 1.11 ± 0.04 when Pi was increased from 0 to 50 mM. Twenty-five millimolar PPi, 50 mM SO4, and 100 mM KCl did not alter the Hill coefficient for PP-ribose-P. In 50 mM Pi, the purine ribonucleotides AMP and GMP increased the Hill coefficient for PP-ribose-P from 1.1 to 1.6 and 1.8 respectively. At Pi concentrations less than 6.25 mM, purine ribonucleotides did not enhance the PP-ribose-P cooperativity which was already demonstrable. Pi at a concentration of 50 mM did not alter the interaction coefficient for AMP or GMP. The S20,w) was 6.2 in both 6.25 mM Pi and 50 mM Pi in the absence of purine ribonucleotides. When both PP-ribose-P and purine ribonucleotides were included in the sucrose-density gradients, Pi did not alter the relative distribution between the small and large forms of the enzyme. It is concluded from these studies that Pi acts as a substrate analogue for PP-ribose-P, and this may explain the mechanism by which Pi modulates the response of amidophosphoribosyltransferase to alterations in the concentrations of PP-ribose-P and purine ribonucleotides.

Human phosphoribosylpyrophosphate (PP-ribose-P) synthetase: properties and regulation.

PP-ribose-P and the enzyme catalyzing its synthesis, PP-riboseP synthetase, were initially discovered by Kornberg, Lieberman and Simms in 1955. PP-ribose-P was subsequently recognized to be an essential substrate for purine, pyridine and pyrimidine biosynthesis, as well as for the formation of other compounds. Recent studies on the control of PP-ribose-P synthesis in bacteria, Ehrlich tumor ascites cells and human erythrocytes have suggested a complicated system of control depending upon ribose-5-P availability, cell energy levels and feedback inhibition from end products. Additional observations have suggested that the intracellular concentration of PP-ribose-P has a critical regulatory role in the biosynthesis of purines de novo in man. In order to clarify the regulation of PP-ribose-P synthesis, we have purified and studied this enzyme from human erythrocytes.KeywordsHuman ErythrocyteApparent Molecular WeightKinetic MechanismSedimentation CoefficientEhrlich Tumor Ascites CellThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Human glltamine phosphoribosylpyrophosphate (PP-ribose-P) amidotransferase: kinetic, regulation and configurational changes.

In a large percentage of patients with gout, hyperuricemia is the result of an increase in the rate of purine biosynthesis de novo (Wyngaarden and Kelley, 1972). Consequently, it is important to understand the molecular basis for the regulation of purine biosynthesis in man.