PGK

Phosphoglycerate kinase (PGK) is a cytosolic enzyme that plays a key role in glycolysis. It catalyzes the reversible transfer of a phosphate group from 1,3-bisphosphoglycerate to adenosine diphosphate (ADP), producing 3-phosphoglycerate and adenosine triphosphate (ATP). This reaction corresponds to substrate-level phosphorylation and occurs late in glycolysis, contributing to ATP generation, especially in tissues with high glycolytic flux or under anaerobic conditions.

Structure and isoforms: PGK is typically a monomer composed of two lobes that close around substrates during catalysis. It is highly conserved across bacteria, archaea, and eukaryotes. In humans, two main isoforms are recognized: PGK1, which is ubiquitously expressed, and PGK2, which is primarily expressed in testis and placenta. The PGK1 gene is the clinically relevant locus, and deficiencies in PGK activity are inherited in an X-linked manner.

Physiological role: By generating ATP directly within glycolysis, PGK supports energy production in cells lacking mitochondrial ATP or under hypoxic conditions. In red blood cells, where glycolysis is a major energy source, PGK activity is particularly important for cell membrane integrity and survival.

Clinical significance: PGK deficiency is a rare genetic disorder presenting as chronic nonspherocytic hemolytic anemia, often with variable additional features such as muscle weakness or myopathy. Diagnosis relies on reduced PGK activity in erythrocytes and confirmation by genetic testing. Treatment is supportive, with management focused on addressing anemia and monitoring for associated symptoms.

Other notes: PGK1 is sometimes used as a housekeeping reference gene in molecular biology due to its consistent expression across many tissues.