Phosphoglycerate mutase

protein
Name=phosphoglycerate mutase 1 (brain)
caption=


width=
HGNCid=8888
Symbol=PGAM1
AltSymbols=PGAMA
EntrezGene=5223
OMIM=172250
RefSeq=NM_002629
UniProt=P18669
PDB=
ECnumber=5.4.2.1
Chromosome=10
Arm=q
Band=25.3
LocusSupplementaryData=protein
Name=phosphoglycerate mutase 2 (muscle)
caption=


width=
HGNCid=8889
Symbol=PGAM2
AltSymbols=
EntrezGene=5224
OMIM=261670
RefSeq=NM_000290
UniProt=P15259
PDB=
ECnumber=5.4.2.1
Chromosome=7
Arm=p
Band=13
LocusSupplementaryData=-p12

Overview

Phosphoglycerate mutase (PGM) is an enzyme that catalyzes step 8 of glycolysis. 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 (2PG) through a 2,3-bisphosphoglycerate intermediate.
This enzyme is not to be confused with Bisphosphoglycerate mutase which catalyzes the conversion of 1,3-bisphosphoglycerate to 2,3-bisphosphoglycerate.

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Mechanism

PGM is a transferase enzyme, effectively transferring a phosphate group (HPO₃^2-) from the C-3 carbon of 3-phosphoglycerate to the C-2 carbon forming 2-phosphoglycerate. It should be noted that 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, the active site contains a phosphohistidine complex formed by phoshphorylation of a specific histidine residue. When 3-phosphoglycerate enters the active site, the phosphohistidine complex is positioned as to facilitate transfer of phosphate from enzyme to substrate C-2 creating a 2,3-bisphosphoglycerate intermediate.
Dephosphorylation of the enzyme histidine actuates a local allosteric change in enzyme configuration which now aligns the substrates 3-C phosphate group with enzyme active site histidine and facilitates phosphate transfer returning the enzyme to its initial phosphorylated state and releasing product 2-phosphoglycerate.

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 mucscle 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.

m-muscle derived

b-brain derived

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 phophoglycerate 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 symtpoms 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.

External links

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