ADPGK

ADPGK Full Name

ADP-dependent glucokinase

ADPGK Introduction

ADP-dependent glucokinase (ADPGK) is a unique and highly conserved metabolic enzyme originally discovered in archaea, but now recognized for its critical biological functions in mammals. Unlike classical hexokinases that strictly utilize ATP as a phosphoryl donor to initiate glucose metabolism, ADPGK catalyzes the phosphorylation of D-glucose to glucose-6-phosphate by exclusively utilizing ADP. This distinctive biochemical property allows the enzyme to function effectively under conditions of severe energy stress—such as ischemia or deep tissue hypoxia—where cellular ATP levels are critically depleted, but ADP is highly abundant.

In human tissues, ADPGK is prominently expressed in highly proliferative cell populations, including hematopoietic cells and actively functioning immune cells like T cells and macrophages. During rapid cell proliferation or immune activation (such as T cell receptor stimulation), ADPGK localizes to the endoplasmic reticulum and acts as a pivotal glucose sensor. It plays an essential role in triggering metabolic reprogramming, specifically facilitating the shift towards aerobic glycolysis (the Warburg effect). By maintaining continuous glycolytic flux when the conventional ATP-dependent hexokinase activity is energetically compromised, ADPGK ensures cell survival and provides the massive biosynthetic precursors and redox balance required for robust cellular responses.

Clinically, the dysregulation of ADPGK is deeply intertwined with cancer progression and tumor immunology. In various highly aggressive malignancies, including clear cell renal cell carcinoma (ccRCC), prostate cancer, and Burkitt's lymphoma, ADPGK is significantly upregulated. Cancer cells hijack this alternative enzyme to adapt to the hostile, nutrient-deprived, and hypoxic tumor microenvironment, thereby promoting robust tumor cell survival, tissue invasion, and metastasis. Interestingly, because of its critical dual role in fueling tumor metabolism and regulating immune cell activation, ADPGK has emerged as a fascinating "double-edged sword" in modern oncology. Researchers are actively targeting ADPGK—where its pharmacological inhibition or genetic knockout induces a catastrophic metabolic collapse in highly glycolytic tumor cells—while also exploring high-ADPGK-expressing tumors as potent sources of neoantigens for personalized cancer vaccines and immunotherapies.

Figure 1. Schematic diagram shows that ADPGK regulates metabolic fitness in PCa progression. (Source: Xu H, et al. 2023)

Alternate Names for ADPGK

ADPGK; ADP-dependent glucokinase; ADP GK; DKFZp434B195; rbBP-35; ATP-dependent glucokinase; ADP-GK; 2610017G09Rik;

• 1. Xu H, et al. ADP-dependent glucokinase controls metabolic fitness in prostate cancer progression. Mil Med Res. 2023 Dec 12;10(1):64.
  2. Li T, et al. Machine learning-based analysis identifies glucose metabolism-related genes ADPGK as potential diagnostic biomarkers for clear cell renal cell carcinoma. Front Oncol. 2025 Sep 16;15:1559887.