Urea synthesis in rat colonocytes is affected by fiber and carcinogen.
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Glutamine plays an important role in cell growth by supplying both energy and nitrogen. In order to understand the mechanisms by which dietary fiber alters colon cancer risk, the effects of dietary fiber and carcinogen on glutamine metabolism in colonie mucosa were investigated. Forty male Sprague Dawley rats received diets containing cellulose or pectin and were injected s.c. with azoxymethane (AOM) or saline. At 36 weeks after injection, isolated colonic mucosal cells were incubated with [U-14C]glutamine (1 or 5 mM) for 60 min. The oxidation of butyrate was higher than that of glutamine in colonocytes from all rats. Production of CO2 from glucose, butyrate and glutamine was lower in rats injected with AOM than with saline and was lower in rats fed cellulose diets than pectin diets. Production of ammonia was higher in AOM-injected rats compared to their saline counterparts. Pectin-feeding resulted in lower amounts of ammonia and glutamate production by colonocytes as compared to cellulose-feeding. Thus, both carcinogen and dietary fiber alter rates of oxidation and deamination of glutamine in rat colonocytes. Concentrations of aspartate were higher in colonocytes from pectin-fed rats than cellulose-fed rats. In contrast, concentrations of citrulline, ornithine and arginine in colonocytes from pectin-fed rats were lower than those from cellulose-fed rats. Citrulline and urea were produced after incubation with glutamine. 14CO2 from 14C-glutamine, but not extracellular [14C]HCO3-, was incorporated into 14C-urea. Higher amounts of 14C-urea were produced by colonocytes from rats fed cellulose compared with pectin feeding which was further increased by AOM treatment. The results suggest the presence of the hitherto unrecognized urea cycle in rat colonocytes which is affected by dietary fiber and carcinogen.
