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the 4th letter of the Roman alphabet (同)d

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deuteriumの化学記号

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2012/12/02 20:14:09」(JST)

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2,3-Bisphosphoglyceric acid (2,3-Bisphosphoglycerate or 2,3-BPG, also known as 2,3-diphosphoglycerate or 2,3-DPG) is a three-carbon isomer of the glycolytic intermediate 1,3-bisphosphoglyceric acid (1,3-BPG). 2,3-BPG is present in human red blood cells (RBC; erythrocyte) at approximately 5 mmol/L. It binds with greater affinity to deoxygenated hemoglobin (e.g. when the red cell is near respiring tissue) than it does to oxygenated hemoglobin (e.g., in the lungs) due to spatial changes: 2,3-BPG (whose size is estimated at about 9 angstroms) fits in the deoxygenated hemoglobin configuration (11 angstroms), but not as well in the oxygenated (5 angstroms). It interacts with deoxygenated hemoglobin beta subunits by decreasing their affinity for oxygen, so it allosterically promotes the release of the remaining oxygen molecules bound to the hemoglobin, thus enhancing the ability of RBCs to release oxygen near tissues that need it most. 2,3-BPG is thus an allosteric effector.

Its function was discovered in 1967 by Reinhold Benesch and Ruth Benesch.^[1]

Metabolism

2,3-BPG is formed from 1,3-BPG by the enzyme 2,3-BPG mutase. It can then be broken down by 2,3-BPG phosphatase to form 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 phosphoglycerate kinase (PGK), generating ATP, or it may be shunted into the Luebering-Rapapport 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 inversely with the pH, which is inhibitory to catalytic action of bisphosphoglyceromutase.

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. Low pH inhibits the activity of biphosphoglyceromutase and activates bisphosphoglyerate phosphatase, which favors generation of ATP.^[2]

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 four 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, which makes easier another subunits’ binding (the first molecule of oxygen helps the following to link).

By 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 feedback loop that can help prevent tissue hypoxia in conditions where it is most likely to occur. Conditions of low tissue oxygen concentration such as high altitude (2,3-BPG levels are higher in those acclimated to high altitudes), airway obstruction, or congestive heart failure will tend to cause RBCs to generate more 2,3-BPG in their effort to generate energy by allowing more oxygen to be released in tissues deprived of 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 tissues with high energetic demands. Bohr effect is another useful way to solve the affinity problem of the hemoglobin, and it is related to the pH and the CO2. It’s important to highlight that the behaviour of myoglobin doesn’t work in the same way, as 2,3-BPG has no effect on it.

Fetal hemoglobin

It is interesting to note that fetal hemoglobin (HbF) exhibits a low affinity for 2,3-BPG, resulting in a higher binding affinity for oxygen. This increased oxygen-binding affinity relative to that of 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. That’s the way O2 flows from the mother to the fetus. As we can see in the following image, fetal hemoglobin has more affinity to oxygen than adult hemoglobin. Moreover, myoglobin has the highest affinity to oxygen.

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]

Iron deficiency anaemia

This illness is characterized by a lack of iron, and as 2,3-BPG needs this chemical element to be synthesized, BPG concentration decreases and hemoglobin binds tightly to oxygen. As a result, oxygen release to tissue is reduced.

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

2,3 BPG during haemodialysis

In a 1998 study, erythrocyte 2,3-BPG concentration was analysed during the haemodialysis process. The 2,3-BPG concentration was expressed relative to the haemoglobin tetramer (Hb4) concentration as the 2,3-BPG/Hb4 ratio. Physiologically, an increase in 2.3-BPG levels would be expected to counteract the hypoxia that is frequently observed in this process. Nevertheless, the results show a 2,3-BPG/Hb4 ratio decreased. This is due to the procedure itself: mechanical stress on the erythrocytes is believed to cause the 2,3-BPG escape, which is then removed by haemodialysis. The concentrations of calcium, phosphate, creatinine, urea and albumin didn’t correlate significantly with the total change in 2,3-BPG/Hb4 ratio. However, the ratio sampled just before dialysis correlated significantly and positively with the total weekly dosage of erythropoietin (main hormone in the erythrocytes formation) given to the patients.^[4]

References

^ Benesch, R.; Benesch, R.E. (1967). "The effect of organic phosphates from the human erythrocyte on the allosteric properties of hemoglobin.". Biochem Biophys Res Commun 26 (2): 162–7. doi:10.1016/0006-291X(67)90228-8. PMID 6030262.
^ Müller-Sterl, W.; Müller-Sterl, W. (2008). "Biochemistry: Fundamentals Of Medicine And The Science Of Life.". Editorial Reverté: 660.
^ González-Cinca N; Pérez de la Ossa P, Carreras J, Climent F (2004). ."Effects of thyroid hormone and hypoxia on 2,3-bisphosphoglycerate, bisphosphoglycerate synthase and phosphoglycerate mutase in rabbit erythroblasts and reticulocytes in vivo"..
^ Nielsen AL; Andersen EM, Jørgensen LG, Jensen HA. (1998). "Oxygen and 2,3 biphosphoglycerate (2,3-BPG) during haemodialysis"..

Berg, J.M., Tymockzko, J.L. and Stryer L. Biochemistry (5th ed). W.H. Freeman and Co, New York, 1995. ISBN 0-7167-4684-0.
-684392408 at GPnotebook
Online medical dictionary
Nelson, David L.; Cox, Michael M.; Lehninger, Albert L. "Principles of Biochemistry (4th ed)". W.H. Freeman, 2005. ISBN 978071674339.
Muller-esterl,W. "Biochemistry: "Fundamentals Of Medicine And The Science Of Life (2nd ed.)". Reverté, 2008. ISBN 84-291-7393-5.
Rodak. "Hematology. Clinical principles and applications (2nd ed.)" Elsevier Science, Philadelphia, 2003. ISBN 950-06-1876-1.
González-Cinca N, Pérez de la Ossa P, Carreras J, Climent F."Effects of thyroid hormone and hypoxia on 2,3-bisphosphoglycerate, bisphosphoglycerate synthase and phosphoglycerate mutase in rabbit erythroblasts and reticulocytes in vivo". Unitat de Bioquímica, Departament de Ciéncies Fisiològiques I, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Universitat de Barcelona, Barcelona, Spain, 2004.
Nielsen AL, Andersen EM, Jørgensen LG, Jensen HA. "Oxygen and 2,3 biphosphoglycerate (2,3-BPG) during haemodialysis". Department of Nephrology, Hvidovre University Hospital, Denmark, 1998.
"Anales de la Real Academia Nacional de Medicina (cuaderno cuarto)". ISSN: 0034-0634

External links

A live model of the effect of changing 2,3 BPG on the oxyhaemoglobin saturation curve

English Journal

Passive transport pathways for Ca(2+) and Co(2+) in human red blood cells. (57)Co(2+) as a tracer for Ca(2+) influx.

Simonsen LO, Harbak H, Bennekou P.SourceDepartment of Biology, University of Copenhagen, August Krogh Building, Denmark.
Blood cells, molecules & diseases.Blood Cells Mol Dis.2011 Dec 15;47(4):214-25. doi: 10.1016/j.bcmd.2011.09.002. Epub 2011 Oct 1.
The passive transport of calcium and cobalt and their interference were studied in human red cells using (45)Ca and (57)Co as tracers. In ATP-depleted cells, with the ATP concentration reduced to about 1μM, the progress curve for (45)Ca uptake at 1mM rapidly levels off with time, consistent with a
PMID 21962619

2-Carboxy-D-arabinitol 1-phosphate (CA1P) phosphatase - evidence for a wider role in plant Rubisco regulation.

Andralojc PJ, Madgwick PJ, Tao Y, Keys A, Ward JL, Beale MH, Loveland JE, Jackson PJ, Willis AC, Gutteridge S, Parry MA.AbstractThe genes for 2-carboxy-D-arabinitol 1-phosphate phosphatase (CA1P phosphatase) from French bean, wheat, Arabidopsis and tobacco were identified and cloned. The deduced protein sequence included an N-terminal motif identical to the phosphogycerate mutase (PGM) active site sequence [LIVM]-x-R-H-G-[EQ]-x-x-[WN]. The corresponding gene from wheat coded for an enzyme with the properties published for CA1P phosphatase. The expressed protein lacked PGM activity but rapidly dephosphorylated 2,3-diphosphoglycerate to 3-phosphoglycerate. DTT activation and GSSG inactivation of this enzyme was pH sensitive, the greatest difference being apparent at pH 8. The presence of the expressed protein during in vitro measurement of Rubisco carboxylase activity prevented a progressive decline in Rubisco turnover. This was due to the removal of an inhibitory bisphosphate which was present in the RuBP preparation, and was found to be D-glycero-2,3-pentodiulose-1,5-bisphosphate (PDBP). The substrate specificity of the expressed protein indicates a role for CA1P phosphatase in the removal of misfire products of Rubisco.
The Biochemical journal.Biochem J.2011 Dec 2. [Epub ahead of print]
The genes for 2-carboxy-D-arabinitol 1-phosphate phosphatase (CA1P phosphatase) from French bean, wheat, Arabidopsis and tobacco were identified and cloned. The deduced protein sequence included an N-terminal motif identical to the phosphogycerate mutase (PGM) active site sequence [LIVM]-x-R-H-G-[EQ
PMID 22132794

[Calcium Pros and Cons Significance and risk of phosphorus supplementation. The necessity of phosphorus supplementation for hypophosphatemia].

Takeda E.SourceInstitute of Health Biosciences, University of Tokushima Graduate School, Japan.
Clinical calcium.Clin Calcium.2011 Dec;21(12):1917-20.
Phosphate plays a vital role forming the high-energy band within ATP. The pathophysiological results of phosphate deficiency are inadequate supplies of energy-rich phosphates and, in particular, inhibition of glyceraldehyde-3- phosphate dehydrogenase, which occupies a key position in glycolysis. The
PMID 22133836

Japanese Journal

<原著>洗浄回収処理血への各種血液保存液添加の効果

上原圭司
近畿大学医学雑誌 36(1), 25-32, 2011-3
… 洗浄回収式自己血輸血装置を用いて洗浄回収処理血を作成し，これに各種の血液保存液を添加して，経時的な変化を赤血球脆弱試験，血清電解質濃度測定，2,3-DPG測定，ATP測定，および光学顕微鏡像により評価した．ATP維持の観点から赤血球若返り液であるAIS液の添加が最も効果的であったが，作成の煩雑さや，投与量に伴うイノシンの腎毒性を考慮すると，解糖系の基質 …
NAID 120003002905

2,3-ジホスホグリセリン酸(2,3-DPG) (広範囲血液・尿化学検査免疫学的検査(第7版・2)その数値をどう読むか) -- (血球化学検査)

高木康
日本臨床 68(-) (970), 878-881, 2010-01
NAID 40016932981

Related Pictures

★リンクテーブル★

国試過去問	「103G010」
リンク元	「エリスロポエチン」「酸素解離曲線」「2,3-ジホスホグリセリン酸」「CPD液」「ラポポート・リューベリングシャント」
関連記事	「D」「DP」「DPG」

「103G010」

2,3-Bisphosphoglyceric acid
	IUPAC name 2,3-Bisphosphoglycerate
	Other names 2,3-Diphosphoglyceric acid; 2,3-Diphosphoglycerate; 2,3-Bisphosphoglycerate
Identifiers
Abbreviations	2,3-BPG; 2,3-DPG; 23BPG
CAS number	138-81-8
PubChem	61
ChemSpider	161681 , 60 (Racemic)
ChEBI	CHEBI:17720
Jmol-3D images	Image 1
	SMILES O=P(O)(OC(C(=O)O)COP(=O)(O)O)O ;
	InChI 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) ; Key: XOHUEYCVLUUEJJ-UWTATZPHSA-N ;
Properties
Molecular formula	C3H8O10P2
Molar mass	266.04 g mol−1
	(verify) (what is: /?); Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
	Infobox references

　　[★]

ヘモグロビン酸素解離曲線が右へシフトするのはどれか。

a. H+濃度の低下
b. Na+濃度の上昇
c. Cl-濃度の上昇
d. CO2濃度の上昇
e. 2,3-DPG濃度の低下

[正答]

※国試ナビ4※　［103G009］←［国試_103］→［103G011］

「エリスロポエチン」

　　[★]

英: erythropoietin EPO EP Ep
同: 赤血球生成促進因子 erythropoiesis-stimulating factor、エリスロポイエチン、ヒトエリスロポエチン human erythropoietin
商: epoetin alfa, Epogen, Procrit

種類

分類

性状

糖タンパク質
34kDa

産生組織

腎臓の傍糸球体細胞

the interstitium of the renal parenchyma, outside the tubular basement membrane , mostly in the inner cortex and outer medulla. (WINTEROBE'S CLINICAL HEMATOLOGY. 209)