2,3-Bisphosphoglyceric acid

Source: Wikipedia, the free encyclopedia.
2,3-Bisphosphoglyceric acid
Names
Preferred IUPAC name
2,3-Bis(phosphonooxy)propanoic acid
Other names
2,3-Diphosphoglyceric acid; 2,3-Diphosphoglycerate; 2,3-Bisphosphoglycerate
Identifiers
3D model (
JSmol
)
Abbreviations 2,3-BPG; 2,3-DPG; 23BPG
ChEBI
ChemSpider
KEGG
UNII
  • InChI=1S/C3H8O10P2/c4-3(5)2(13-15(9,10)11)1-12-14(6,7)8/h2H,1H2,(H,4,5)(H2,6,7,8)(H2,9,10,11)/t2-/m1/s1 checkY
    Key: XOHUEYCVLUUEJJ-UWTATZPHSA-N checkY
  • Key: XOHUEYCVLUUEJJ-UWTATZPHBL
  • O=P(O)(OC(C(=O)O)COP(=O)(O)O)O
Properties
C3H8O10P2
Molar mass 266.035 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
☒N verify (what is checkY☒N ?)

2,3-Bisphosphoglyceric acid (

conjugate base 2,3-bisphosphoglycerate) (2,3-BPG), also known as 2,3-diphosphoglyceric acid (conjugate base 2,3-diphosphoglycerate) (2,3-DPG), is a three-carbon isomer of the glycolytic intermediate 1,3-bisphosphoglyceric acid
(1,3-BPG).

D-2,3-BPG is present in human red blood cells (RBC;

allosteric effector
.

Its function was discovered in 1967 by

Ruth Benesch.[1]

Metabolism

2,3-BPG is formed from

3-phosphoglycerate. Its synthesis and breakdown are, therefore, a way around a step of glycolysis
, with the net expense of one ATP per molecule of 2,3-BPG generated as the high-energy carboxylic acid-phosphate mixed anhydride bond is cleaved by bisphosphoglycerate mutase.

The normal glycolytic pathway generates 1,3-BPG, which may be dephosphorylated by

Luebering-Rapoport pathway, where bisphosphoglycerate mutase catalyzes the transfer of a phosphoryl group from C1 to C2 of 1,3-BPG, giving 2,3-BPG. 2,3-BPG, the most concentrated organophosphate in the erythrocyte, forms 3-PG by the action of bisphosphoglycerate phosphatase
. The concentration of 2,3-BPG varies proportionately to the [H+].

There is a delicate balance between the need to generate ATP to support energy requirements for cell metabolism and the need to maintain appropriate oxygenation/deoxygenation status of hemoglobin. This balance is maintained by isomerisation of 1,3-BPG to 2,3-BPG, which enhances the deoxygenation of hemoglobin.

Effects of binding

Oxygen-haemoglobin dissociation curve

When 2,3-BPG binds to deoxyhemoglobin, it acts to stabilize the low oxygen affinity state (T state) of the oxygen carrier. It fits neatly into the cavity of the deoxy- conformation, exploiting the molecular symmetry and positive polarity by forming salt bridges with lysine and histidine residues in the ꞵ subunits of hemoglobin. The R state, with oxygen bound to a heme group, has a different conformation and does not allow this interaction.

By itself, hemoglobin has sigmoid-like kinetics. In selectively binding to deoxyhemoglobin, 2,3-BPG stabilizes the T state conformation, making it harder for oxygen to bind hemoglobin and more likely to be released to adjacent tissues. 2,3-BPG is part of a

congestive heart failure will tend to cause RBCs to generate more 2,3-BPG, because changes in pH and oxygen modulate the enzymes that make and degrade it.[2] The accumulation of 2,3-BPG decreases the affinity of hemoglobin for oxygen. Ultimately, this mechanism increases oxygen release from RBCs under circumstances where it is needed most. This release is potentiated by the Bohr effect, in which hemoglobin's binding affinity for oxygen is also reduced by a lower pH and high concentration of carbon dioxide. In tissues with high energetic demands, oxygen is rapidly consumed, which increases the concentration of H+ and carbon dioxide. Through the Bohr effect, hemoglobin is induced to release more oxygen to supply cells that need it. In contrast, 2,3-BPG has no effect on the related compound myoglobin
.(reference required)

In pregnant women, there is a 30% increase in intracellular 2,3-BPG. This lowers the maternal hemoglobin affinity for oxygen, and therefore allows more oxygen to be offloaded to the fetus in the maternal uterine arteries. The fetus has a low sensitivity to 2,3-BPG, so its hemoglobin has a higher affinity for oxygen. Therefore, although the pO2 in the uterine arteries is low, the fetal umbilical artery (which carries deoxygenated blood) can still get oxygenated from them.

Fetal hemoglobin

adult hemoglobin (HbA) is due to HbF's having two α/γ dimers as opposed to the two α/β dimers of HbA. The positive histidine residues of HbA β-subunits that are essential for forming the 2,3-BPG binding pocket are replaced by serine
residues in HbF γ-subunits. Like that, histidine nº143 gets lost, so 2,3-BPG has difficulties in linking to the fetal hemoglobin, and it looks like the pure hemoglobin. Increased binding affinity of fetal hemoglobin relative to HbA facilitates the passage of oxygen across the placental membrane from the mother to the fetus.

Differences between myoglobin (Mb), fetal hemoglobin (Hb F), adult hemoglobin (Hb A)

Diseases related to 2,3-BPG

Hyperthyroidism

A 2004 study checked the effects of thyroid hormone on 2,3-BPG levels. The result was that the hyperthyroidism modulates in vivo 2,3-BPG content in erythrocytes by changes in the expression of phosphoglycerate mutase (PGM) and 2,3-BPG synthase. This result shows that the increase in the 2,3-BPG content of erythrocytes observed in hyperthyroidism doesn’t depend on any variation in the rate of circulating hemoglobin, but seems to be a direct consequence of the stimulating effect of thyroid hormones on erythrocyte glycolytic activity.[3]

Chronic anemia

Red cells increase their intracellular 2,3-BPG concentration as much as five times within one to two hours in patients with chronic anemia, when the oxygen carrying capacity of the blood is diminished. This results in a rightward shift of the oxygen dissociation curve and more oxygen being released to the tissues.

Chronic respiratory disease with

hypoxia

Recently, scientists have found similarities between low amounts of 2,3-BPG with the occurrence of

high altitude pulmonary edema
at high altitudes.

CONCENTRATION OF 2,3-BPG ERYTHROCYTE FOUND IN DIFFERENT CLINICAL SITUATIONS STUDIED
n Hb (g/dl) 2,3-BPG (mM)
1 Normality 120 14.2 ± 1.6 4.54 ± 0.57
2 Hyperthyroidism 35 13.7 ± 1.4 5.66 ± 0.69
3 Iron deficiency anaemia 40 10.0 ± 1.7 5.79 ± 1.02
4 Chronic respiratory disease with hypoxia 47 16.4 ± 2.2 5.29 ± 1.13

Hemodialysis

In a 1998 study, erythrocyte 2,3-BPG concentration was analyzed during the

erythrocyte formation) given to the patients.[4]

See also

References

  1. PMID 6030262
    .
  2. PMID 10477268
    .
  3. S2CID 34271262
    .
  4. PMID 9832337
    .

External links
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