Ribose 5-phosphate

R5P consists of a five-carbon sugar, ribose, and a phosphate group at the five-position carbon. It can exist in open chain form or in furanose form. The furanose form is most commonly referred to as ribose 5-phosphoric acid. == Biosynthesis ==

The formation of R5P is highly dependent on the cell growth and the need for NADPH (Nicotinamide adenine dinucleotide phosphate), R5P, and ATP (Adenosine triphosphate). Formation of each molecule is controlled by the flow of glucose 6-phosphate (G6P) in two different metabolic pathways: the pentose phosphate pathway and glycolysis. The relationship between the two pathways can be examined through different metabolic situations. Pentose phosphate pathway R5P is produced in the pentose phosphate pathway in all organisms. (e.g. fatty acid synthesis) and pentose sugars. The pathway consists of two phases: an oxidative phase that generates NADPH and a non-oxidative phase that involves the interconversion of sugars. In the oxidative phase of PPP, two molecules of NADP+ are reduced to NADPH through the conversion of G6P to ribulose 5-phosphate (Ru5P). In the non-oxidative of PPP, Ru5P can be converted to R5P through ribose-5-phosphate isomerase enzyme catalysis. When demand for NADPH and R5P is balanced, G6P forms one Ru5P molecule through the PPP, generating two NADPH molecules and one R5P molecule. Glycolysis When more R5P is needed than NADPH, R5P can be formed through glycolytic intermediates. Glucose 6-phosphate is converted to fructose 6-phosphate (F6P) and glyceraldehyde 3-phosphate (G3P) during glycolysis. Transketolase and transaldolase convert two molecules of F6P and one molecule of G3P to three molecules of R5P. During rapid cell growth, higher quantities of R5P and NADPH are needed for nucleotide and fatty acid synthesis, respectively. Glycolytic intermediates can be diverted toward the non-oxidative phase of PPP by the expression of the gene for pyruvate kinase isozyme, PKM. PKM creates a bottleneck in the glycolytic pathway, allowing intermediates to be utilized by the PPP to synthesize NADPH and R5P. This process is further enabled by triosephosphate isomerase inhibition by phosphoenolpyruvate, the PKM substrate. == Function ==

R5P and its derivatives serve as precursors to many biomolecules, including DNA, RNA, ATP, coenzyme A, FAD (Flavin adenine dinucleotide), and histidine. Nucleotide biosynthesis Nucleotides serve as the building blocks for nucleic acids, DNA and RNA. They are composed of a nitrogenous base, a pentose sugar, and at least one phosphate group. Nucleotides contain either a purine or a pyrimidine nitrogenous base. All intermediates in purine biosynthesis are constructed on a R5P "scaffold". R5P also serves as an important precursor to pyrimidine ribonucleotide synthesis. During nucleotide biosynthesis, R5P undergoes activation by ribose-phosphate diphosphokinase (PRPS1) to form phosphoribosyl pyrophosphate (PRPP). Formation of PRPP is essential for both the de novo synthesis of purines and for the purine salvage pathway. The de novo synthesis pathway begins with the activation of R5P to PRPP, which is later catalyzed to become phosphoribosylamine, a nucleotide precursor. During the purine salvage pathway, phosphoribosyltransferases add PRPP to bases. PRPP also plays an important role in pyrimidine ribonucleotide synthesis. During the fifth step of pyrimidine nucleotide synthesis, PRPP covalently links to orotate at the one-position carbon on the ribose unit. The reaction is catalyzed by orotate phosphoriboseyltransferase (PRPP transferase), yielding orotidine monophosphate (OMP). Other functions R5P can be converted to adenosine diphosphate ribose, which binds and activates the TRPM2 ion channel. The reaction is catalyzed by ribose-5-phosphate adenylyltransferase == Disease relevance ==

Diseases have been linked to R5P imbalances in cells. Cancers and tumors show upregulated production of R5P correlated to increased RNA and DNA synthesis. is also linked to an imbalance of R5P. Although the molecular pathology of the disease is poorly understood, hypotheses included decreased RNA synthesis. Another disease linked to R5P is gout. Higher levels of G6P lead to a buildup of glycolytic intermediates, that are diverted to R5P production. R5P converts to PRPP, which forces an overproduction of purines, leading to uric acid build up. The build up is caused by a deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT), which leads to decreased nucleotide synthesis and an increase of uric acid production. Superactivity in PRPS1, the enzyme that catalyzes the R5P to PRPP, has also been linked to gout, as well as neurodevelopmental impairment and sensorineural deafness. == References ==