Ribose moiety, purine synthesis

PRPP is an "activated pentose" that participates in the synthesis of purines and pyrimidines, and in the salvage of purine bases (see p. 294). Synthesis of PRPP from ATP and ribose 5-phosphate is catalyzed by PRPP synthetase (ribose phosphate pyrophosphokinase, Figure 22.6). This enzyme is activated by inorganic phosphate (Pi) and inhibited by purine nucleotides (end-product inhibition). [Note The sugar moiety of PRPP is ribose, and therefore ribonucleotides are the end products of de novo purine synthesis. When deoxy-ribonucleotides are required for DNA synthesis, the ribose sugar moiety is reduced (see p. 295).]... 

Figure 7-20. De novo synthesis of purines and pyrimidines. Ribonucleotide reductase (R.R.) catalyzes the reduction of the ribose moiety in ADP, GDP, and CDP to deoxyribose. The source of each of the atoms is indicated in the boxes at the bottom of the figure. In hereditary orotic aciduria, the enzymes converting orotate to UMP are defective ( ).

Purine bases can be converted to ribonucleotides via phosphoribosyl-transferases PP-ribose-P provides the ribosyl phosphate moiety. Purine nucleosides can be phosphorylated by ATP-requiring nucleoside kinases to form the same ribonucleotides. Finally, the possibility also exists that purine bases are first converted to ribonucleosides via nucleoside phos-phorylase, and then to ribonucleotides by the above-mentioned kinases. These routes of ribonucleotide synthesis are summarized as follows ... 

Pentose sugars are required for the synthesis of nucleic acids. Ribose 5-phosphate is utilized in the synthesis of purine and pyrimidine deoxyribo- and ribo-nucleotides. Since neonatal and fetal thymuses are highly active in nucleic acid synthesis, these tissues have an active pentose phosphate pathway to furnish ribose 5-phosphate. Ribose moieties also feature in the structure of major coenzymes such as NAD(P), coenzyme A and FAD (Figure 5.3). The degradation of nucleic acids and nucleotides... 

Purine nucleotides can be synthesized in three ways By de novo synthesis, by reconstruction from purine bases through the addition of a ribose phosphate moiety, or by phosphory-... 

De novo purine nucleotide synthesis proceeds by the synthesis of the purine base upon the ribose sugar moiety. 

Ribose phosphates phosphorylated derivatives of ribose. Ribose is phosphorylated in position 5 by the action of ribokinase (EC 2.7.1.15) and ATP ribose 5-phosphate is also produced in the Pentose phosphate cycle (see), and in the Calvin c cle (see) of photosynthesis. Phosphoribomutase cat yses the interconversion of ribose 5-phospbate and ribose 1-phosphate, and the cosubstrate of this reaction is ribose l,5-f>isphosphate. 5-Phosphoribosyl 1-pyrophos-phate donates a ribose 5-phosphate moiety in the de novo biosynthesis of purine and pyrimidine nucleotides (see Purine biosynthesis. Pyrimidine biosynthesis), in the Salvage pathway (see) of purine and pyrimidine utilization, in the biosynthesis of L-Histi-dine (see) and L-Tryptophan (see) and in the conversion of nicotinic acid into nicotinic acid ribotide (see Pyridine nucleotide cycle). Ribose 1-phosphate can also take part in nucleotide synthesis (see Salvage pathway). 

It was not until 1953 that Goldwasser (9) and Williams and Buchanan (10) showed that purine bases could be converted to ribonucleotides by a one-step process, without the intermediate formation of ribonucleosides. The source of the ribose phosphate moiety was discovered in 1955 to be PP-ribose-P in the course of studies of adenylate synthesis by Kornberg et al. 11), and of inosinate synthesis by Korn et al. 12) extracts of yeast, beef liver, and pigeon liver were employed. The enzymes involved were at first called nucleotide pyrophosphorylases, but are now known as purine phosphoribosyltransferases. The general reaction is... 

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