PGK1
PGK1 (phosphoglycerate kinase 1) is a glycolytic enzyme that catalyses one of the two ATP-producing steps of glycolysis. It is also a moonlighting protein, with roles that extend beyond metabolism, including activity as a protein kinase in the mitochondrion. Browse Assay Genie's current range of PGK1 research reagents below, or read on for the biology behind the target.
PGK1 catalyses the reversible conversion of 1,3-diphosphoglycerate to 3-phosphoglycerate, one of the two ATP-producing reactions in the glycolytic pathway. Both L- and D- forms of purine and pyrimidine nucleotides can serve as substrates, although activity on pyrimidines is much lower. The enzyme belongs to the phosphoglycerate kinase family and is found in the cytosol and in the mitochondrial matrix.
Beyond glycolysis, PGK1 is described as a moonlighting protein, meaning it performs mechanistically distinct functions. It appears to act as a polymerase alpha cofactor (primer recognition protein). When localised to the mitochondrion, it acts as a protein kinase and phosphorylates pyruvate dehydrogenase kinase PDK1. This inhibits pyruvate dehydrogenase complex activity and suppresses the formation of acetyl-coenzyme A from pyruvate, so it inhibits oxidative phosphorylation and promotes glycolysis. PGK1 may also play a role in sperm motility.
Tumour cells secrete PGK1, where it contributes to angiogenesis by reducing disulphide bonds in the serine protease plasmin. This leads to release of angiostatin, an inhibitor of tumour blood vessel growth. Deficiency of the enzyme is associated with a wide range of clinical phenotypes, including haemolytic anaemia and neurological impairment. The PGK1 gene lies on the X chromosome, and pseudogenes have been defined on chromosomes 19, 21 and the X chromosome. Mouse and rat each have a Pgk1 ortholog.
PGK1 catalyses a core ATP-generating step of glycolysis, making it a reference enzyme for studying glycolytic flux.
Mitochondrial PGK1 phosphorylates PDK1, inhibiting the pyruvate dehydrogenase complex and shifting metabolism from oxidative phosphorylation towards glycolysis.
Secreted PGK1 reduces disulphide bonds in plasmin, leading to angiostatin release and linking the enzyme to tumour blood vessel regulation.
PGK1 deficiency is associated with haemolytic anaemia and neurological impairment, making the protein relevant to studies of X-linked metabolic disease.
PGK1 catalyses the reversible conversion of 1,3-diphosphoglycerate to 3-phosphoglycerate, generating ATP in glycolysis. It also acts as a polymerase alpha cofactor and, in mitochondria, as a protein kinase that phosphorylates PDK1 to inhibit the pyruvate dehydrogenase complex and promote glycolysis.
NCBI Gene describes PGK1 as a moonlighting protein because it performs mechanistically distinct functions. Besides its glycolytic role, it may act as a polymerase alpha cofactor, as a mitochondrial protein kinase, and as a secreted protein in tumour angiogenesis that releases angiostatin from plasmin.
Mouse and rat both have a Pgk1 ortholog, so the gene is conserved in common model species. PGK1 deficiency is associated with haemolytic anaemia and neurological impairment. Check the datasheet of any product for its validated reactivity.
Other glycolytic enzymes, mitochondrial metabolism regulators such as PDK1, and angiogenesis markers with products at Assay Genie.
Gene and protein annotations from HGNC, NCBI Gene and UniProt P00558; product specifications from Assay Genie datasheets.