[Frontiers in Bioscience 16, 1331-1343, January 1, 2011]

Channelling of arginine in NO and polyamine pathways in colonocytes and consequences

Francois Blachier1, Anne Marie Davila1, Robert Benamouzig1,2, Daniel Tome1

1INRA, AgroParisTech, CRNH-IdF, UMR 914 Nutrition Physiology and Ingestive Behavior, 16 rue Claude Bernard, Paris, France, 2Department of Gastroenterology, Hopital Avicenne, Assistance Publique-Hopitaux de Paris, Bobigny, France

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Metabolism and physiological effects of polyamines and nitric oxide on normal and cancerous colonic epithelial cells
3.1. Metabolism of L-arginine in the polyamine and nitric oxide pathways in normal and cancerous colonic epithelial cells
3.2. Exogenous sources of polyamines for colonic epithelial cells: the synthesis of polyamines by the microbiota
3.3. Uptake, metabolism and release of polyamines by normal and cancerous colonic epithelial cells
3.4. Synthesis of polyamines and cancerous colonic epithelial cell growth
3.5. Exogenous nitric oxide exerts anti-proliferative effect on cancerous colonic epithelial cell growth
3.6. Effects of nitric oxide on ornithine decarboxylase catalytic activity: the channelling hypothesis
3.7. Metabolism of agmatine in normal and cancerous colonic epithelial cells
3.8. Effects of agmatine on the growth of cancerous colonic epithelial cells
4. Conclusion
5. Acknowledgment
6. References

1. ABSTRACT

Colon epithelium is renewed within few days through asymmetric mitosis of pluripotent cells followed by differentiation and exfoliation. Absorptive colonocytes do not transport amino acids from lumen to bloodstream but import amino acids from plasma. Among amino acids, colonocytes can use L-arginine as a precursor for nitric oxide (NO) synthesis and also for polyamine synthesis through the stepwise conversion of L-arginine into L-ornithine and urea, conversion of L-ornithine into putrescine and then synthesis of spermidine and spermine. Colonic epithelial cells can transport polyamines produced exogenously by the microbiota. Polyamines are strictly necessary for undifferentiated colonic epithelial cell proliferation but NO exerts anti-proliferative effect on these cells raising the view that the channelling of arginine in the nitric oxide and polyamine pathways is involved in the control of cellular proliferation. Furthermore, NO has been shown to be a potent inhibitor of ornithine decarboxylase activity in colonic epithelial cells. Unbalance of the chanelling of arginine in the NO and polyamine pathways in colonic cancerous epithelial cells as a determinant promoting their proliferation is discussed.