Document Detail

Proline metabolism and microenvironmental stress.
MedLine Citation:
PMID:  20415579     Owner:  NLM     Status:  MEDLINE    
Proline, the only proteinogenic secondary amino acid, is metabolized by its own family of enzymes responding to metabolic stress and participating in metabolic signaling. Collagen in extracellular matrix, connective tissue, and bone is an abundant reservoir for proline. Matrix metalloproteinases degrading collagen are activated during stress to make proline available, and proline oxidase, the first enzyme in proline degradation, is induced by p53, peroxisome proliferator-activated receptor gamma (PPARgamma) and its ligands, and by AMP-activated protein kinase downregulating mTOR. Metabolism of proline generates electrons to produce ROS and initiates a variety of downstream effects, including blockade of the cell cycle, autophagy, and apoptosis. The electrons can also enter the electron transport chain to produce adenosine triphosphate for survival under nutrient stress. Pyrroline-5-carboxylate, the product of proline oxidation, is recycled back to proline with redox transfers or is sequentially converted to glutamate and alpha-ketoglutarate. The latter augments the prolyl hydroxylation of hypoxia-inducible factor-1alpha and its proteasomal degradation. These effects of proline oxidase, as well as its decreased levels in tumors, support its role as a tumor suppressor. The mechanism for its decrease is mediated by a specific microRNA. The metabolic signaling by proline oxidase between oxidized low-density lipoproteins and autophagy provides a functional link between obesity and increased cancer risk.
James M Phang; Wei Liu; Olga Zabirnyk
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural; Review    
Journal Detail:
Title:  Annual review of nutrition     Volume:  30     ISSN:  1545-4312     ISO Abbreviation:  Annu. Rev. Nutr.     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-07-21     Completed Date:  2010-10-04     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8209988     Medline TA:  Annu Rev Nutr     Country:  United States    
Other Details:
Languages:  eng     Pagination:  441-63     Citation Subset:  IM    
Metabolism and Cancer Susceptibility Section, Laboratory of Comparative Carcinogenesis, Center for Cancer Research, NCI at Frederick, Frederick, Maryland 21702, USA.
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MeSH Terms
AMP-Activated Protein Kinases / metabolism
Apoptosis / physiology
Autophagy / physiology
Collagen / metabolism*
Gene Expression Regulation, Enzymologic*
Intracellular Signaling Peptides and Proteins / metabolism
Matrix Metalloproteinases / metabolism*
PPAR gamma / metabolism
Proline / metabolism*
Proline Oxidase / genetics,  metabolism*
Protein-Serine-Threonine Kinases / metabolism
Reactive Oxygen Species / metabolism
Signal Transduction
Tumor Suppressor Protein p53 / metabolism
Grant Support
HHSN27612080001//PHS HHS
Reg. No./Substance:
0/Intracellular Signaling Peptides and Proteins; 0/PPAR gamma; 0/Reactive Oxygen Species; 0/Tumor Suppressor Protein p53; 147-85-3/Proline; 9007-34-5/Collagen; EC 1.5.3.-/Proline Oxidase; EC 2.7.1.-/mTOR protein; EC Protein Kinases; EC Kinases; EC 3.4.24.-/Matrix Metalloproteinases

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