D i.e. Hyoxanthine2, 3 Bisphosphoglycerate (2, 3- BPG) or 2, 3 Diphosphoglycerate 2, 3- DPG)It is most abundant organic phosphate in RBC5 where its concentration is approximately that of hemoglobin. It is synthesized from glycolytic intermediates 3-phosplzoglyceraldehyde by means of Rapopo- leubering shunt.It is highly charged anion that binds to the /3 chains of deoxy hemoglobin. One mole of deoxyhemoglobin binds to one mole of 2, 3 BPG. A single molecule of 2, 3 - BPG binds to a positively charged pocket (cavity) formed by two 13-chains, in the centre of deoxyhemoglobin. Positively charged aminoacids of pocket form ionic bonds with negatively charged phosphate group of 2, 3- BPG.It decreases 02 affinity of hemoglobin by binding to deoxyhemoglobin but not to oxyhemoglobin and stabilizing the taut conformation of deoxy hemoglobin.Oxyhemoglobin + 2, 3 - BPG ____________ Deoxyhemoglobin + 02(HbO2) (Hb - 2, 3 - BPG)In this equilibrium, an increase in the concentration of 2, 3 - BPG shifts the reaction to right causing more oxygen to be released.Hemoglobin from which 2, 3 - BPG is removed has a high affinity for oxygen. However, the presence of 2, 3 - BPG significantly reduces the affinity of hemoglobin for oxygen, shifting the oxygen dissociation curve to right. This reduced affinity enable hemoglobin to releases oxygen efficiently at the paial pressure found in tissues.Role of 2, 3 - BPG in stored & transfused blood: ?Storing blood in acid- citrate - dextrose leads to a decrease of 2, 3- BPG in RBC. Hemoglobin deficient in 2, 3 - BPG displays an abnormally high 02 affinity & fails to unload its bound 02 in tissues properly and thus acts as an oxygen trap rather than as oxygen transpo system. However, transfused RBCs are able to restore their depleted supplies of 2, 3BPG in 24-48 hours; this may be a serius issue in critically ill patiens. This decrease in 2, 3 - BPG can be prevented by adding inosine (hypoxanthine - ribose) to the storage mediumQ. Uncharged inosine molecule enters RBC, releases its ribose moiety, gets phosphorylated and enters HMP pathway to become 2, 3-BPG. Hypoxanthine is formed during utilization of inosine to maintain or increase 2, 3 - BPG content. Thus while inosine increase/ maintain 2, 3 - BPG content, hypoxanthine does notQ.In chronic hypoxia & anemia the concentration of 2, 3- BPG increases whereas, when pH falls (or is low), 2 3- BPG concentration falls because acidosis inhibits red cell glycolysis.Increasing 2, 3 - BPGChronic hypoxia eg- Obstructive pulmonary emphysema- High altitudes- Cyanotic congenital hea diseaseAnemia eg sickle cell HbAcidosis (1- pH)Exercise (in non athletes)Harmones- Thyroid hormone- Growth hormone- AndrogensPregnancyRejuvenating chemical agentsInosineQDihydroxyacetonePyruvatePhosphatePhosphoenol, pyruvate