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

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.