Phosphoglycolate phosphatase

Phosphoglycolate phosphatase(PGP), also commonly referred to as phosphoglycolate hydrolase, 2-phosphoglycolate phosphatase, P-glycolate phosphatase, and phosphoglycollate phosphatase, is an enzyme responsible for catalyzing the conversion of 2-phosphogylcolate into glycolate and phosphate. First studied and purified within plants, phosphoglycolate phosphatase plays a major role in photorespiratory 2-phosphoglycolate metabolism, an essential pathway for photosynthesis in plants. The occurrence of photorespiration in plants, due to the lack of substrate specificity of rubisco, leads to the formation of 2-phospoglycolate and 3-phosphogylcerate(PGA). PGA is the normal product of carboxylation and will enter the Calvin cycle. Phosphogylcolate, which is a potent inhibitor of phosphofructokinase and triosephosphate isomerase, must be quickly metabolized and transformed into a useful substrate, and phosphoglycolate phosphatase catalyzes the first step in the regeneration of 3-phosphogylcerate from 2-phosphoglycolate at the expense of energy in the form of ATP.

phosphoglycolate phosphatase
Identifiers
EC no.	3.1.3.18
CAS no.	9025-76-7
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Gene Ontology	AmiGO / QuickGO
Search PMC articles PubMed articles NCBI proteins

Since the discovery of its activity in plants, it has been purified within the cytoplasm of human erythrocytes and implicated in 2,3-DPG regulation.

Enzyme Structure

9 structures have been solved for this class of enzymes, with PDB accession codes 1TE2, 1WR8, 2HDO, 2HI0, 4BKM, 2YY6, 1KYT, 1L6R, and 2NYV.

Enzyme Mechanism

This enzyme belongs to the family of hydrolases(TAG), specifically those acting on phosphoric monoester bonds. 

2-phosphoglycolate + H₂O  $\leftrightharpoons$ glycolate + phosphate

Biological Function

Plant

It was previously believed that the evolution of the photorespiratory glycolate mechanism that involves phosphoglycolate phosphatase was essential for photosynthesis in more complex plants and unnecessary for cyanobacteria because of their ability to concentrate CO₂ and therefore, avoid photorespiration, similar to C4 plants. However, the finding of three different phosphoglycolate metabolism pathways within the model cyanobacterium Synechocystis sp. strain PCC 6803 implicates that cyanobacteria were not only the evolutionary origin of oxygenic photosynthesis but also ancient photorespiratory phosphoglycolate metabolism, which might have been conveyed endosymbiotically to plants.

Drawing on earlier research that indicated the presence of phosphogylcolic acid in algae through labeling of C¹⁴O₂ and P²⁸-orthophosphate, Richardson & Tolbert were the first to find a phosphatase activity specific for phosphoglycolate in tobacco leaves. 

Mammalian

Partial purification analysis has shown that human erythrocytes contain phosphoglycolate phosphatase as a cytoplasmic dimeric enzyme with molecular weight of 72,000. Approximately 5% of the enzyme’s total activity is membrane-associated. It shows optimum pH of 6.7 and has a Michaelis constant of 1 mM for phosphoglycolate. The activity of the enzyme is Mg2+-dependent. Co2+, and to a smaller extent Mn2+, may substitute for Mg2+. Moreover, it needs a univalent cation for optimum activity. 

In 1977, Badwey first demonstrated phosphoglycolate phosphatase activity in human erythrocytes and speculated that the enzyme’s activity may function to protect red cells from inadvertently formed phosphoglycolate, yet no studies had conclusively found phosphoglycolate present in mammalian red blood cells. The implication of phosphogylcolate phosphatase’s role in human red blood cells was discovered when its substrate, phosphoglycolate, was shown to be a potent activator of the enzyme 2,3-bisphosphoglycerate phosphatase(2,3-DPG), another hydrolase which catalyzes the metabolic reaction of 2,3-Bisphosphoglycerate to 3-phosphoglycerate. In the presence of 0.02 mM phosphoglycolate, the phosphatase activity of DPGM is activated more than 1000-fold. In all animal tissues, 2,3-PGA is important as the cofactor of the glycolytic enzyme, phosphoglycerate mutase.

More important, the synthesis and breakdown of 2,3-PGA is critical to regulation of hemoglobin’s binding affinity to oxygen, and an increase in its concentration leads to increased tissue oxygenation while a decrease may lead to tissue hypoxia. Therefore, the activation of the enzyme responsible for the metabolic breakdown of 2,3-PGA by phosphoglycolate could implicate phosphoglycolate phosphatase in the regulation of 2,3-PGA concentrations.

Human Isozymes

Phosphoglycolate phosphatase exhibits electrophoretically distinctive variant forms. Found in all human tissues, including red cells, lymphocytes, and cultured fibroblasts, the highest enzymatic activity was noted within skeletal and cardiac muscle. Research into the genetic polymorphism indicates that PGP is likely determined by three alleles at a single autosomal locus, which is expressed in all human tissues. Preliminary observations of fetal tissue suggest that the PGP locus is also fully expressed during intra-uterine life. Research has also shown appreciable genetic variation indicated by the detection of 6 phenotypes within a small European population.

References

• Christeller JT, Tolbert NE (1978). "Phosphoglycolate phosphatase. Purification and properties". J. Biol. Chem. 253 (6): 1780–5. PMID 204630.