Overview

Phosphoglycerate mutase (PGM) is an enzyme

Enzyme

Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...

 that catalyzes step 8 of glycolysis

Glycolysis

Glycolysis is the metabolic pathway that converts glucose C6H12O6, into pyruvate, CH3COCOO− + H+...

. It catalyzes the internal transfer of a phosphate group from C-3 to C-2 which results in the conversion of 3-phosphoglycerate (3PG) to 2-phosphoglycerate

2-Phosphoglycerate

2-Phosphoglyceric acid , or 2-phosphoglycerate, is a glyceric acid which serves as the substrate in the ninth step of glycolysis. It is catalyzed by enolase into phosphoenolpyruvate , the penultimate step in the conversion of glucose to pyruvate.-In Glycolysis: -References:...

 (2PG) through a 2,3-bisphosphoglycerate intermediate.

This enzyme is not to be confused with Bisphosphoglycerate mutase

Bisphosphoglycerate mutase

Bisphosphoglycerate mutase is an enzyme unique to erythrocytes and placental cells. It is responsible for the catalytic synthesis of 2,3-Bisphosphoglycerate from 1,3-bisphosphoglycerate...

 which catalyzes the conversion of 1,3-bisphosphoglycerate

1,3-Bisphosphoglycerate

1,3-Bisphosphoglyceric acid is a 3-carbon organic molecule present in most, if not all, living organisms. It primarily exists as a metabolic intermediate in both glycolysis during respiration and the Calvin cycle during photosynthesis...

 to 2,3-bisphosphoglycerate

2,3-Bisphosphoglycerate

2,3-Bisphosphoglyceric acid is a three-carbon isomer of the glycolytic intermediate 1,3-bisphosphoglyceric acid . 2,3-BPG is present in human red blood cells at approximately 5 mmol/L...

.

Mechanism

PGM is a transferase

Transferase

In biochemistry, a transferase is an enzyme that catalyzes the transfer of a functional group from one molecule to another . For example, an enzyme that catalyzed this reaction would be a transferase:In this example, A would be the donor, and B would be the acceptor...

 enzyme, effectively transferring a phosphate group

Phosphate

A phosphate, an inorganic chemical, is a salt of phosphoric acid. In organic chemistry, a phosphate, or organophosphate, is an ester of phosphoric acid. Organic phosphates are important in biochemistry and biogeochemistry or ecology. Inorganic phosphates are mined to obtain phosphorus for use in...

 (HPO₃^2-) from the C-3 carbon of 3-phosphoglycerate to the C-2 carbon forming 2-phosphoglycerate

2-Phosphoglycerate

2-Phosphoglyceric acid , or 2-phosphoglycerate, is a glyceric acid which serves as the substrate in the ninth step of glycolysis. It is catalyzed by enolase into phosphoenolpyruvate , the penultimate step in the conversion of glucose to pyruvate.-In Glycolysis: -References:...

. The reaction involves two separate phosphoryl groups and the ending phosphate on the 2-carbon is not the same phosphate removed from the 3-carbon.

In the enzyme's initial state

Enzyme

Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...

, the active site

Active site

In biology the active site is part of an enzyme where substrates bind and undergo a chemical reaction. The majority of enzymes are proteins but RNA enzymes called ribozymes also exist. The active site of an enzyme is usually found in a cleft or pocket that is lined by amino acid residues that...

 contains a phosphohistidine complex formed by phoshphorylation

Phosphorylation

Phosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation activates or deactivates many protein enzymes....

 of a specific histidine

Histidine

Histidine Histidine, an essential amino acid, has a positively charged imidazole functional group. It is one of the 22 proteinogenic amino acids. Its codons are CAU and CAC. Histidine was first isolated by German physician Albrecht Kossel in 1896. Histidine is an essential amino acid in humans...

 residue. When 3-phosphoglycerate enters the active site

Active site

In biology the active site is part of an enzyme where substrates bind and undergo a chemical reaction. The majority of enzymes are proteins but RNA enzymes called ribozymes also exist. The active site of an enzyme is usually found in a cleft or pocket that is lined by amino acid residues that...

, the phosphohistidine complex is positioned as to facilitate transfer of phosphate from enzyme to substrate C-2 creating a 2,3-bisphosphoglycerate

2,3-Bisphosphoglycerate

2,3-Bisphosphoglyceric acid is a three-carbon isomer of the glycolytic intermediate 1,3-bisphosphoglyceric acid . 2,3-BPG is present in human red blood cells at approximately 5 mmol/L...

 intermediate.

Dephosphorylation

Dephosphorylation

Dephosphorylation is the essential process of removing phosphate groups from an organic compound by hydrolysis. Its opposite is phosphorylation...

 of the enzyme

Enzyme

Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...

 histidine

Histidine

Histidine Histidine, an essential amino acid, has a positively charged imidazole functional group. It is one of the 22 proteinogenic amino acids. Its codons are CAU and CAC. Histidine was first isolated by German physician Albrecht Kossel in 1896. Histidine is an essential amino acid in humans...

 actuates a local allosteric change in enzyme configuration which now aligns the substrates 3-C phosphate group with enzyme

Enzyme

Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...

 active site

Active site

In biology the active site is part of an enzyme where substrates bind and undergo a chemical reaction. The majority of enzymes are proteins but RNA enzymes called ribozymes also exist. The active site of an enzyme is usually found in a cleft or pocket that is lined by amino acid residues that...

 histidine

Histidine

Histidine Histidine, an essential amino acid, has a positively charged imidazole functional group. It is one of the 22 proteinogenic amino acids. Its codons are CAU and CAC. Histidine was first isolated by German physician Albrecht Kossel in 1896. Histidine is an essential amino acid in humans...

 and facilitates phosphate transfer returning the enzyme

Enzyme

Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...

 to its initial phosphorylated state and releasing product 2-phosphoglycerate

2-Phosphoglycerate

2-Phosphoglyceric acid , or 2-phosphoglycerate, is a glyceric acid which serves as the substrate in the ninth step of glycolysis. It is catalyzed by enolase into phosphoenolpyruvate , the penultimate step in the conversion of glucose to pyruvate.-In Glycolysis: -References:...

.

Reaction Summary

3PG + P-Enzyme → 2,3BPG + Enzyme → 2PG + P-Enzyme

   3-phosphoglycerate         intermediate          2-phosphoglycerate

ΔG°′=+1.1kcal/mol

Isozymes

Phosphoglycerate mutase exists primarily as a dimer of two either identical or closely related subunits of about 32kDa. The enzyme is found in organisms as simple as yeast through homo sapiens and its structure is highly conserved throughout. (Yeast PGM≈74% conserved vs mammal form).


In mammals, the enzyme subunits appear to be either a muscle-derived form (m-type) or other tissue (b-type for brain where the b-isozyme was originally isolated). Existing as a dimer, the enzyme then has 3 isozymes depending on which subunit forms makeup the whole molecule (mm, bb or mb). The mm-type is found mainly in smooth muscle almost exclusively. The mb-isozyme is found in cardiac and skeletal muscle and the bb-type is found in the rest of tissues. While all three isozymes may be found in any tissue, the above distributions are based on prevalence in each.

Regulation

Phosphoglycerate mutase has a small positive Gibbs free energy and this reaction proceeds easily in both directions. Since it is a reversible reaction, it is not the site of major regulation mechanisms or regulation schemes for the glycolytic pathway.

Deficiency

In humans, deficiency in phosphoglycerate mutase function presents as a metabolic myopathy and is one of the many forms of syndromes formerly referred to as muscular dystrophy. Dysfunction in the activity of phosphoglycerate mutase is an autosomal recessive genetic disorder with symptoms ranging from mild to moderate, is not thought life-threatening and can be managed with changes in lifestyle.

Onset is generally noted as childhood to early adult though some who may be mildy affected by the disorder may not know they have it. The symptoms are an intolerance to physical exertion or activity, cramps and muscle pain. Uncommonly, myoglobinuria may be present. Permanent weakness is rare. The disease is not progressive and has an excellent prognosis.

Human proteins containing this domain

BPGM; PFKFB1

PFKFB1

6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 1 is an enzyme that in humans is encoded by the PFKFB1 gene.-Further reading:...

; PFKFB2

PFKFB2

6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 is an enzyme that in humans is encoded by the PFKFB2 gene.-Further reading:...

; PFKFB3

PFKFB3

6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 is an enzyme that in humans is encoded by the PFKFB3 gene.-Further reading:...

; PFKFB4

PFKFB4

6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4 also known as PFKFB4 is a enzyme which in humans is encoded by the PFKFB4 gene.- Function :...

; PGAM1; PGAM2;
PGAM4; PGAM5; STS1; UBASH3A

UBASH3A

Ubiquitin-associated and SH3 domain-containing protein A is a protein that in humans is encoded by the UBASH3A gene.-Further reading:...

;