The metabolism of proline, a stress substrate, modulates carcinogenic pathways.

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Phang JM, Donald SP, Pandhare J, Liu Y

The metabolism of proline, a stress substrate, modulates carcinogenic pathways.

Amino Acids. 2008 Nov;35(4):681-90. doi: 10.1007/s00726-008-0063-4. Epub 2008 Apr 10.

PubMed ID

18401543 [ View in PubMed

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Abstract

The resurgence of interest in tumor metabolism has led investigators to emphasize the metabolism of proline as a "stress substrate" and to suggest this pathway as a potential anti-tumor target. Proline oxidase, a.k.a. proline dehydrogenase (POX/PRODH), catalyzes the first step in proline degradation and uses proline to generate ATP for survival or reactive oxygen species for programmed cell death. POX/PRODH is induced by p53 under genotoxic stress and initiates apoptosis by both mitochondrial and death receptor pathways. Furthermore, POX/PRODH is induced by PPARgamma and its pharmacologic ligands, the thiazolidinediones. The anti-tumor effects of PPARgamma may be critically dependent on POX/PRODH. In addition, it is upregulated by nutrient stress through the mTOR pathway to maintain ATP levels. We propose that proline is made available as a stress substrate by the degradation of collagen in the microenvironmental extracellular matrix by matrix metalloproteinases. In a manner analogous to autophagy, this proline-dependent process for bioenergetics from collagen in extracellular matrix can be designated "ecophagy".

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Proline	Proline dehydrogenase 1, mitochondrial	Protein	Humans	Unknown	Substrate	Details