Glycerol kinase (GK)

Glycerol kinase (GK) is a fundamental metabolic enzyme that catalyzes the ATP-dependent phosphorylation of glycerol to sn-glycerol 3-phosphate (UniProt P32189). This reaction is a critical step that bridges lipid and carbohydrate metabolism, allowing glycerol to enter pathways for gluconeogenesis or triglyceride synthesis (Wikipedia). GK is predominantly expressed in the liver and kidneys, though it also plays roles in other tissues like the testis and brain (UniProt). In addition to its enzymatic activity, GK exhibits moonlighting functions, such as acting as a nuclear corepressor for the orphan receptor NR4A1 to regulate hepatic glucose homeostasis (PubMed 30821173). Genetic mutations in the GK gene cause glycerol kinase deficiency (GKD), an X-linked recessive disorder that leads to hyperglycerolemia and hyperglyceroluria (NIH). A common clinical challenge in GKD is pseudohypertriglyceridemia, where elevated glycerol levels interfere with standard triglyceride assays, often leading to unnecessary lipid-lowering treatments (NIH). While no specific drugs are currently approved to target human GK, it is being explored as a therapeutic target for managing type 2 diabetes and obesity (AARMEDICA). Furthermore, the glycerol kinase of Plasmodium falciparum is a target of interest for developing new antimalarial agents, such as isoquinoline derivatives (ResearchGate).

Other names

GlycerokinaseATP:glycerol 3-phosphotransferaseGKPGKDGlycerol kinase 1

Catalyzes the ATP-dependent phosphorylation of glycerol to sn-glycerol 3-phosphate; also functions as a transcriptional coregulator through protein-protein interactions in the nucleus.