Target intelligence / Profile preview

Arginine metabolism

Molecular classification
Other
01

Overview

Arginine metabolism refers to the network of biochemical pathways involving the synthesis, catabolism, and utilization of the amino acid L‑arginine. It is not a single molecule or receptor but encompasses several key enzymes—such as arginases, nitric oxide synthases (NOS), argininosuccinate synthetase (ASS), argininosuccinate lyase (ASL), and others—that regulate cellular levels of arginine and its downstream metabolites. These pathways are critical for producing nitric oxide, urea, polyamines, proline, creatine, agmatine, and other bioactive molecules essential for cell growth, immune function, vascular tone regulation, neurotransmission, and nitrogen disposal[1][3][7]. In cancer biology—especially in tumors with low ASS expression—targeting enzymes involved in arginine metabolism has emerged as a therapeutic strategy by depriving tumor cells that are auxotrophic for exogenous arginine. In immunology and inflammation research, differential routing through NOS versus ARG impacts macrophage polarization toward pro-inflammatory or tissue-repair phenotypes[1]. Because "Arginine metabolism" is a pathway rather than a discrete molecular target or receptor protein—and includes many distinct enzymes—it should not be considered a canonical drug target itself. If you require structured information on specific proteins within this pathway—for example "Arginase 1," "Nitric oxide synthase 2," etc.—please specify which enzyme or transporter you wish to focus on. “In mammalian cells…arginine can be catabolized by four classes of enzymes…Although the enzymes are regulated…and expressed in a cell-type-specific manner…the metabolism…is potentially complex since its downstream metabolites encompass NO [nitric oxide], urea,…ornithine,…citrulline,…creatine,…agmatine,…glutamate,…proline…and polyamines.” [1]

02

Mechanism of action

Enzyme inhibition or depletion of arginine to starve tumor cells[4][5] Modulation of nitric oxide synthase activity to alter NO signaling[1][3]

03

Biological functions

Amino acid biosynthesisNitric oxide productionUrea cyclePolyamine synthesisCell proliferation and survival
04

Disease associations

CancerImmune response modulationCardiovascular disease
05

Safety considerations

Systemic amino acid depletion can cause toxicity, including immune suppression and impaired wound healing[2]Potential for off-target effects due to the central role of arginine in multiple metabolic pathways[7]
06

Interacting drugs

Arginase inhibitors (e.g., CB-1158)

3 more in the full profile.

07

Biomarkers

Expression levels of argininosuccinate synthetase 1 (ASS1)[2]Plasma/serum arginine concentration

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