Structural Biochemistry/Enzyme Catalytic Mechanism/Regulation/Regulation by 2,3-bisphosphoglycerate

2,3-bisphosphoglycerate is a three-carbon molecule with two negatively charged (2-) phosphate groups attached to the central carbon, forming a tetrahedral structure. This highly anionic molecule is most commonly found in the red blood cells at about the same concentration as that of hemoglobin (around 2 mM); this is responsible for the great efficiency of oxygen transport that takes place in hemoglobin molecules. 2,3-bisphosphoglycerate, abbreviated as 2,3-BPG and also referred to as 2,3-diphosphoglycerate (2,3-DPG), binds with greater affinity to deoxygenated hemoglobin typically found in tissues than to oxygenated hemoglobin found in the lungs. Pure hemoglobin releases only 8% of oxygen to the tissues, however hemoglobin with 2,3-BPG allows it to release 66% of the oxygen to the tissues. It is for this reason that hemoglobin, and not myoglobin, is more used in transferring oxygen between tissues and the lungs. There are high concentrations of 2,3-BPG found in erythrocytes

Glucose Metabolism
2,3-biphosphoglycerate is the product of glucose metabolism. It is formed from 1,3-BPG by the enzyme bisphosphoglycerate mutase. It can form 3-phosphoglycerate from when it is broken down by phosphotase. This synthesis and disassembling takes several steps.

Properties
2,3-bisphosphoglycerate is mostly found in human red blood cells, or erythrocytes. It has a less oxygen binding affinity to oxygenated hemoglobin than it does to deoxygenated hemoglobin. It also acts to stabilize the oxygen affinity of the hemoglobin in the tense state, since the oxygen affinity is low. This is due to the position of the 2,3-BPG molecule in the central cavity of the deoxyhemoglobin tetramer, where the 2,3-BPG interacts with the positively charged molecules on each beta chain within the deoxyhemoglobin. As a result, the conformation of the deoxyhemoglobin is altered in such a way that a greater number or concentration of oxygen molecules is needed to bind to the free sites in the deoxyhemoglobin, thereby giving hemoglobin a lower affinity T state until addition of more oxygen. This effect makes it difficult for oxygen to bind to the hemoglobin which allows it be released to areas with low oxygen concentration. This is why hemoglobin is such an effective oxygen carrier. It is able to saturate itself with oxygen at high oxygen level in the lungs and retain the oxygen until it reaches the tissues which has a lower oxygen concentration. However, this does not occur in the relaxed (R) state since the hemoglobin is oxygenated. Thus, 2,3-bisphosphoglycerate helps in the regulation of the oxygen carrying capacity in hemoglobin. The R state conformation of deoxyhemoglobin does not allow for these interactions due to the oxygen bound to the heme group. During the T state to R state transition, the 2,3-bisphophoglycerate is released. It's vital to oxygen transfer, since the T state must be stabilized until the transition point. However, the T state is very unstable resulting for hemoglobin's affinity for oxygen and thus tries to bind to oxygen, disrupting the T state. Without 2,3-BPG, this stabilization cannot occur thanks to its inhibition abilities.

2,3-BPG can also function as an intermediate of phosphoglycerate mutase. The enzyme is used in the Embden-Meyerhof pathway of glycolysis in erythrocytes. The pathway is the anaerobic metabolic pathway that converts glycogen to lactic acid in human muscle.

The effect of 2,3-bisphosphoglycerate is shown between the fetal red cells and the maternal red cells. The maternal red cells are able to bind 2,3-bisphosphoglycerate better than the fetal red cells. Therefore the fetal red cells have a higher oxygen affinity which explains why oxygen flows from oxyhemoglobin to the fetal deoxyhemoglobin. Since the fetal red cells contain a higher oxygen affinity, it allows oxygen to be carried to the placenta. Soon after birth, humans have regular hemoglobin. One of the reasons that fetal cells contain a higher affinity for oxygen is because fetal hemoglobin do not contain a beta subunit, but instead a gamma subunit. Therefore the pocket that binds BPG differs which lowers the affinity for BPG while inducing higher oxygen binding.