Enzymes in arginine and proline metabolic pathways

The enzymes in the arginine and proline metabolic pathways constitute a critical metabolic axis that regulates the interconversion of several key amino acids, including arginine, proline, ornithine, and glutamate [1, 6]. Key enzymes in this network include arginase (ARG1/2), nitric oxide synthase (NOS), ornithine decarboxylase (ODC), and proline dehydrogenase (PRODH), which collectively regulate the urea cycle, polyamine biosynthesis, and the production of nitric oxide [8, 9]. In many cancers, these pathways are reprogrammed; for instance, certain tumors lack argininosuccinate synthetase 1 (ASS1) and become "arginine auxotrophs," making them susceptible to arginine-depleting therapies like pegargiminase [2, 11]. Additionally, enzymes such as arginase and proline dehydrogenase are targeted to modulate the tumor microenvironment or disrupt metabolic adaptations required for metastasis [1, 7]. Beyond oncology, these enzymes are vital in treating urea cycle disorders and cardiovascular conditions, though therapeutic intervention requires careful management of systemic nitrogen levels and immune function [8, 9].

Other names

Arginine and proline metabolismGlutamine-arginine-proline axisUrea cycle enzymesProline metabolic pathwayKEGG pathway map00330

Therapeutic strategies include enzymatic depletion of extracellular arginine (arginine deprivation), inhibition of arginase to prevent arginine consumption by myeloid cells, and inhibition of ornithine decarboxylase to block polyamine synthesis [1, 2, 9].