Proline metabolism in health and disease

Abstract

Traditionally, proline is categorized as one of the nonessential amino acids in mammals, however, proline is indispensable in the neonatal small intestine. In addition, proline has features of an inhibitory neuromodulator and a metabolic precursor for glutamate in glutamatergic synapses in the central nervous system. Importantly, recent studies have shown that the gene PRODH1, which encodes proline oxidase (POX) the first enzyme in the proline catabolic pathway, is one of a handful of genes whose expression is induced by p53, a pivotal tumor suppressor. Subsequent work has demonstrated that the increased amounts of POX together with availability of proline results in increased reactive oxygen production that can lead to mitochondriaand caspase 8-mediated apoptosis. These perturbations may play a key role in oncogenesis in certain types of cell and tissue. In bacteria and plants, proline serves as an osmoprotectant to assist in maintaining appropriate osmotic pressure and participates in balancing redox potential and the pH. Proline metabolism in mammals involves two other amino acids, glutamate and ornithine, and five enzymatic activities, D-pyrroline-5-carboxylate (P5C) reductase (P5CR), POX, P5C dehydrogenase (P5CDH), P5C synthase (P5CS) and ornithine-d-aminotransferase (OAT). With the exception of OAT, which catalyzes a reversible reaction, the other four enzymes are unidirectional, suggesting that proline metabolism is purpose-driven, tightly regulated, and compartmentalized. This tri-amino-acid system also links with three other essential metabolic systems, namely the TCA cycle, urea cycle, and pentose phosphate pathway. Abnormalities in proline metabolism are relevant in several diseases: six monogenic inborn errors involving metabolism and/or transport of proline and its immediate metabolites have been described and mouse models are available for some of these. In addition, impaired proline metabolism has been implicated as a susceptibility factor for schizophrenia, a complex neuropsychiatric disorder with a frequency of *1% around the world. The International Symposium on ‘‘Proline metabolism in health and disease’’ has been held twice (in 2004 and 2007) in the past 4 years. Both meetings brought together leaders in research involving all aspects of proline metabolism and its relationship to human disease. After the second symposium, the meeting participants reasoned that after some 40 years of research on proline metabolism in different organisms and in humans in health and disease, a publication summarizing the area is needed. We feel grateful that the journal Amino Acids agreed to publish our peer-reviewed manuscripts and abstracts in this special issue. The contents of this issue have been grouped into four main sections:

DOI: 10.1007/s00726-008-0102-1
02040602008200920102011201220132014201520162017
Citations per Year

103 Citations

Semantic Scholar estimates that this publication has 103 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@article{Hu2008ProlineMI, title={Proline metabolism in health and disease}, author={Chien-an A. Hu and James M . . Phang and David Valle}, journal={Amino Acids}, year={2008}, volume={35}, pages={651-652} }