ADP-dependent glucokinase (ADPGK)

ADP-dependent glucokinase (ADPGK) is an enzyme (EC 2.7.1.147) that catalyzes the phosphorylation of D-glucose to glucose-6-phosphate using ADP (rather than ATP) as the phosphoryl donor[1][2][4]. It belongs to the transferase family, specifically the phosphotransferases with an alcohol group as an acceptor[4]. Uniquely, ADPGK is found both in Archaea and metazoans but is structurally distinct from classical hexokinases, featuring a ribokinase-like fold[1][2]. In human cells, ADPGK is highly expressed in various tissues, including both normal and tumor tissues[1][2][3]. Its canonical metabolic function is context-dependent: while not a major contributor to glycolysis under normal conditions, ADPGK becomes important under metabolic stress—such as hypoxia or impaired hexokinase activity—where it can support cell survival[2][3][5]. In T cells, it localizes to the endoplasmic reticulum, where it triggers a metabolic switch towards aerobic glycolysis upon receptor stimulation, facilitating reactive oxygen species (ROS) generation, and supporting activation-induced gene expression[2][3][5]. ADPGK is also implicated in glycosylation processes critical for immune signaling[5]. ADPGK has been proposed as a disease-relevant metabolic modulator in cancer and immunity: its upregulation is noted in various cancer types, and its deficiency precipitates metabolic dysfunction and apoptosis, particularly in immune cells[3][5]. There are currently no approved drugs known to target ADPGK directly, nor established mechanisms of drug action specifically for this enzyme. Biomarkers related to ADPGK include its expression/activity as a marker of T-cell activation and ER stress. Safety concerns are primarily associated with total loss-of-function scenarios, leading to catastrophic loss of metabolic and glycosylation capacity[5].

Other names

ADP-GKPSEC0260DKFZp434B195RbBP-352610017G09RikADP-specific glucokinaserbBP-35