Arginine deiminase pathway (ADI pathway)

Arginine deiminase pathway Overview

The arginine deiminase pathway is a metabolic route found primarily in bacteria and some anaerobic eukaryotes. It breaks down arginine into ornithine, ammonium, and carbon dioxide while generating ATP from ADP and phosphate. The pathway involves the sequential action of three enzymes: arginine deiminase (ADI), ornithine transcarbamylase (OTC), and carbamate kinase (CK)[1][4][5]. This pathway enables microorganisms to survive in low-oxygen and acidic environments, providing a key energy source and protection from acidic stress[1][4]. The produced ammonium helps counteract environmental acidity. In pathogenic microorganisms, the pathway has been implicated in virulence and infection processes[5]. Therapeutically, arginine-depleting enzymes derived from the ADI pathway (notably, pegylated ADI/ADI-PEG20) have emerged as promising agents for the treatment of cancers that are arginine auxotrophs—especially those lacking ASS1 expression, which makes them unable to synthesize arginine de novo. Targeting the pathway deprives tumor cells of external arginine, causing metabolic stress, cell cycle arrest, autophagy, and apoptosis, and can sensitize tumors to chemotherapy and radiotherapy[2][3][6][8]. Note on correctness: The "arginine deiminase pathway" itself is not a single molecular target but rather a series of enzymatic steps carried out by distinct enzymes (ADI, OTC, CK). Therefore, while enzymes in this pathway are validated therapeutic targets, the pathway itself is not a drug target per se[1][5]. The entry "arginine deiminase pathway" is thus incorrect as a canonical drug target and should be resolved to its constituent enzymes (argine deiminase, etc.) for structured target curation.

Mechanism of Action

Arginine depletion (starvation), Induction of cell cycle arrest, Promotion of autophagy and apoptosis, Immune modulation

Biological Functions

Safety Considerations

Interacting Drugs

Associated Biomarkers