Bisphosphoglyceric acid

Carboxylic acids. Aliphatic carboxylic acids (R—GOOH) are deprotonated at physiological pH (pH 7) and are therefore represented as R—COO. Thus, acetic acid (GHj—COOH) exists as acetate (CH3COO ) at pH 7. A variety of short chain mono-, di-and tricarboxylic acids are important intermediates in metabolism and may be present at low concentrations in all cells either as the acid or as a covalent adduct. Thus, acetate (C2) and malonate (C3) can exist as the key acyl-coenzyme A thioester intermediates acetylGoA and malonylCoA, respectively. Phosphoenolpyruvate (C3), 1,3-bisphosphoglyceric acid (C3) and 3-phosphoglyc,erate (C3) are key metabolic intermediates. 

Abbreviations (listed alphabetically) l,3bPGA, 1,3-bisphosphoglyceric acid 20G, 2-oxoglutaric acid 3PGA, 3-phosphoglyceric acid acetylCoA, acetyl coenzyme A ADP/ATP, adenosine diphosphate and triphosphate ADPGlu, adenosine diphosphate glucose AOX, alternative oxidase Aqp, aquaporin Ca, atmospheric CO2 Cc, chloroplast CO2 Ci, intercellular CO2 cl, mitochondrial Complex 1 cll, mitochondrial Complex 11 cll, mitochondrial Complex 111 clV, mitochondrial Complex IV (cytochrome oxidase) cV, mitochondrial Complex V (ATP Synthase) citrate, citric acid CoA, coenzyme A E4P,... 

Glyceraldehyde 3-phosphate is oxidized to a carboxylic acid and then phosphorylated to yield 1,3-bisphosphoglycerate. 

Like all anhydrides (Section 21.5), the mixed carboxylic-phosphoric anhydride is a reactive substrate in nucleophilic acyl (or phosphoryl) substitution reactions. Reaction of 1,3-bisphosphoglycerate with ADR occurs in step 7 by substitution on phosphorus, resulting in transfer of a phosphate group to ADP and giving ATP plus 3-phosphoglycerate. The process is catalyzed by phospho-gjvcerate kinase and requires Mg2+ as cofactor. Together, steps 6 and 7 accomplish the oxidation of an aldehyde to a carboxylic acid. 

J4. Joulin, V., Peduzzi, J., Remeo, P.-H., Rosa, R., Valentin, C., Dubart, A., Lapeyre, B Blouquit, Y., Garel, M.-C., Goossens, M., Rosa, J., and Cohen-Solal, M., Molecular cloning and sequence of the human erythrocyte 2,3-bisphosphoglycerate mutase cDNA Revised amino acid sequence. EM BO J. 5, 2275-2283 (1986). 

Some patients with erythrocytosis (excess RBCs) have a mutation that converts a lysine to alanine at amino acid 82 in the 3 subunit of hemoglobin. This particular lysine normally protrudes into the central cavity of deoxyhemoglobin, where it participates in binding 2,3-bisphosphoglycerate (BPG). 

The formation of 1,3-bisphosphoglycerate involves the synthesis of a high-energy phosphate bond as the aldehyde of glyceraldehyde 3-phosphate is oxidized to a carboxylic acid and then phosphorylated by reaction with inorganic phosphate. 

A requirement for all fermentations is the existence of a mechanism for coupling ATP synthesis to the fermentation reactions. In the lactic acid and ethanol fermentations this coupling mechanism consists of the formation of the intermediate 1,3-bisphosphoglycerate by the glyceraldehyde 3-phosphate dehydrogenase (Fig. 10-3, step a). This intermediate contains parts of both the products ATP and lactate or ethanol. 

Step 6 involves the oxidation of D-glyceraldehyde 3-phosphate, accompanied by phosphorylation of the intermediate carboxylic acid, to produce D-l,3-bisphosphoglycerate. The enzyme is glyceral-dehyde-3-phosphate dehydrogenase. 

This table can be helpful in estimating the pATs of other weak acids from their structures. In using this table it is important to remember that -log [H ] is used in the expression for the acid dissociation constant in terms of pH. To obtain pKs based on -log y (H ) [H ], add 0,0.08, 0.11,0.12, and 0.14 at ionic strengths of 0, 0.05, 0.10,0.15, and 0.25 M, respectively, at 298.15 K as indicated by Table 1.3. PaddedForm rounds the output to two figures to the right of the decimal point. There is a list of full names of reactants in the Appendix of this book. The reactants bpg, nmn, pep, and prpp are bisphosphoglycerate, nicotinamidemononucleotide, phosphoenolpyruvate, and 5-phosphoribosyl-alpha-pyrophosphate, respectively. 

Bisphosphoglycerate is an acyl phosphate, which is a mixed anhydride of phosphoric acid and a carboxylic acid. Such compounds have a high phosphoryl-transfer potential one of its phosphoryl groups is transferred to ADP in the next step in glycolysis. 

Bisphosphoglycerate is also responsible for the apparent change in hemoglobin (increased oxygen affinity) when blood is stored in an acid-citrate-dextrose medium. Under these conditions, glycolysis stops and the synthesis of BPG stops. However, the degradation of BPG continues, with a resultant drop in BPG concentration. The situation cannot be reversed by... 

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