Ribose

Ribose as its 5-phosphate ester is typically produced from glucose by the pentose phosphate pathway. In at least some archaea, alternative pathways have been identified. Ribose can be synthesized chemically, but commercial production relies on fermentation of glucose. Using genetically modified strains of B. subtilis, 90 g/liter of ribose can be produced from 200 g of glucose. The conversion entails the intermediacy of gluconate and ribulose. Ribose has been detected in meteorites. == Structure ==

Ribose is an aldopentose (a monosaccharide containing five carbon atoms that, in its open chain form, has an aldehyde functional group at one end). In the conventional numbering scheme for monosaccharides, the carbon atoms are numbered from C1' (in the aldehyde group) to C5'. The deoxyribose derivative found in DNA differs from ribose by having a hydrogen atom in place of the hydroxyl group at C2'. This hydroxyl group performs a function in RNA splicing. The "-" in the name -ribose refers to the stereochemistry of the chiral carbon atom farthest away from the aldehyde group (C4'). In -ribose, as in all -sugars, this carbon atom has the same configuration as in -glyceraldehyde. File:Alpha-D-Ribopyranose numbered.png|α--Ribopyranose File:Beta-D-Ribopyranose numbered.png|β--Ribopyranose File:Alpha-D-Ribofuranose numbered.png|α--Ribofuranose File:Beta-D-Ribofuranose Numbered.png|β--Ribofuranose Relative abundance of forms of ribose in solution: β--ribopyranose (59%), α--ribopyranose (20%), β--ribofuranose (13%), α--ribofuranose (7%) and open chain (0.1%). For ribose residues in nucleosides and nucleotide, the torsion angles for the rotation encompassing the bonds influence the configuration of the respective nucleoside and nucleotide. The secondary structure of a nucleic acid is determined by the rotation of its 7 torsion angles. Having a large amount of torsion angles allows for greater flexibility. In closed ring riboses, the observed flexibility mentioned above is not observed because the ring cycle imposes a limit on the number of torsion angles possible in the structure. This puckering is achieved by displacing an atom from the plane, relieving the strain and yielding a more stable conformation. When only a single atom is displaced, it is referred to as an "envelope" pucker. When two atoms are displaced, it is referred to as a "twist" pucker, in reference to the zigzag orientation. In an "endo" pucker, the major displacement of atoms is on the β-face, the same side as the C4'-C5' bond and the base. In an "exo" pucker, the major displacement of atoms is on the α-face, on the opposite side of the ring. The major forms of ribose are the 3'-endo pucker (commonly adopted by RNA and A-form DNA) and 2'-endo pucker (commonly adopted by B-form DNA). These ring puckers are developed from changes in ring torsion angles; there are infinite combinations of angles so therefore, there is an infinite number of transposable pucker conformations, each separated by disparate activation energies. == Functions ==

ATP is derived from ribose; it contains one ribose, three phosphate groups, and an adenine base. ATP is created during cellular respiration from adenosine diphosphate (ATP with one less phosphate group). Signaling pathways Ribose is a building block in secondary signaling molecules such as cyclic adenosine monophosphate (cAMP) which is derived from ATP. One specific case in which cAMP is used is in cAMP-dependent signaling pathways. In cAMP signaling pathways, either a stimulative or inhibitory hormone receptor is activated by a signal molecule. These receptors are linked to a stimulative or inhibitory regulative G-protein. When a stimulative G-protein is activated, adenylyl cyclase catalyzes ATP into cAMP by using Mg2+ or Mn2+. cAMP, a secondary messenger, then goes on to activate protein kinase A, which is an enzyme that regulates cell metabolism. Protein kinase A regulates metabolic enzymes by phosphorylation which causes a change in the cell depending on the original signal molecule. The opposite occurs when an inhibitory G-protein is activated; the G-protein inhibits adenylyl cyclase and ATP is not converted to cAMP. Metabolism Ribose is referred to as the "molecular currency" because of its involvement in intracellular energy transfers. For example, nicotinamide adenine dinucleotide (NAD), flavin adenine dinucleotide (FAD), and nicotinamide adenine dinucleotide phosphate (NADP) all contain the -ribofuranose moiety. They can each be derived from -ribose after it is converted to -ribose 5-phosphate by the enzyme ribokinase. NAD, FAD, and NADP act as electron acceptors in biochemical redox reactions in major metabolic pathways including glycolysis, the citric acid cycle, fermentation, and the electron transport chain. Nucleotide biosynthesis Nucleotides are synthesized through salvage or de novo synthesis. Nucleotide salvage uses pieces of previously made nucleotides and re-synthesizes them for future use. In de novo, amino acids, carbon dioxide, folate derivatives, and phosphoribosyl pyrophosphate (PRPP) are used to synthesize nucleotides. Both de novo and salvage require PRPP which is synthesized from ATP and ribose 5-phosphate by an enzyme called PRPP synthetase. == Modifications ==

Modifications in nature Ribokinase catalyzes the conversion of -ribose to -ribose 5-phosphate. Once converted, -ribose-5-phosphate is available for the manufacturing of the amino acids tryptophan and histidine, or for use in the pentose phosphate pathway. The absorption of -ribose is 88–100% in the small intestines (up to 200 mg/kg·h). One important modification occurs at the C2' position of the ribose molecule. By adding an O-alkyl group, the nuclear resistance of the RNA is increased because of additional stabilizing forces. These forces are stabilizing because of the increase of intramolecular hydrogen bonding and an increase in the glycosidic bond stability. The resulting increase of resistance leads to increases in the half-life of siRNA and the potential therapeutic potential in cells and animals. Synthetic modifications Along with phosphorylation, ribofuranose molecules can exchange their oxygen with selenium and sulfur to produce similar sugars that only vary at the 4' position. These derivatives are more lipophilic than the original molecule. Increased lipophilicity makes these species more suitable for use in techniques such as PCR, RNA aptamer post-modification, antisense technology, and for phasing X-ray crystallographic data. Similar to the 2' modifications in nature, a synthetic modification of ribose includes the addition of fluorine at the 2' position. This fluorinated ribose acts similar to the methylated ribose because it is capable of suppressing immune stimulation depending on the location of the ribose in the DNA strand. The big difference between methylation and fluorination, is the latter only occurs through synthetic modifications. The addition of fluorine leads to an increase in the stabilization of the glycosidic bond and an increase of intramolecular hydrogen bonds. == Medical uses ==

-ribose has been suggested for use in management of congestive heart failure (as well as other forms of heart disease) and for chronic fatigue syndrome (CFS), also called myalgic encephalomyelitis (ME) in an open-label non-blinded, non-randomized, and non-crossover subjective study. Supplemental -ribose can bypass part of the pentose phosphate pathway, an energy-producing pathway, to produce -ribose-5-phosphate. The enzyme glucose-6-phosphate-dehydrogenase (G-6-PDH) is often in short supply in cells, but more so in diseased tissue, such as in myocardial cells in patients with cardiac disease. The supply of -ribose in the mitochondria is directly correlated with ATP production; decreased -ribose supply reduces the amount of ATP being produced. Studies suggest that supplementing -ribose following tissue ischemia (e.g. myocardial ischemia) increases myocardial ATP production, and therefore mitochondrial function. Essentially, administering supplemental -ribose bypasses an enzymatic step in the pentose phosphate pathway by providing an alternate source of 5-phospho--ribose 1-pyrophosphate for ATP production. Supplemental -ribose enhances recovery of ATP levels while also reducing cellular injury in humans and other animals. One study suggested that the use of supplemental -ribose reduces the instance of angina in men with diagnosed coronary artery disease. -Ribose has been used to treat many pathological conditions, such as chronic fatigue syndrome, fibromyalgia, and myocardial dysfunction. It is also used to reduce symptoms of cramping, pain, stiffness, etc. after exercise and to improve athletic performance. == References ==