Small gut mucosal activities of pyrimidine precursor enzymes in celiac disease

Abstract

Summary The increased mitotic cell count in the small intestinal mucosa in celiac disease has given rise to question as to whether increased cell turnover or prolonged mitosis were occurring. Two enzymes in the pyrimidine biosynthetic pathway, aspartate carbamoyl transferase and dihydroorotate dehydrogenase, have been measured in rat and human intestinal mucosa. Activities of aspartate carbamoyl transferase in normal mucosa obtained at surgery were 247 ± 114 nmoles per g per min. No inhibition of activity of this enzyme was noted after addition of cytidine mono-, di-, or triphosphate. Dihydroorotate dehydrogenase activity was 18.1 ± 9.2 nmoles per g per min from intestinal mucosa obtained at surgery. Peroral biopsy samples from normal subjects showed aspartate carbamoyl transferase activity of 282 ± 142 nmoles and dihydroorotate dehydrogenase activity of 9.9 ± 8.6 nmoles per g per min. Mucosa obtained from patients with celiac disease snowed normal or elevated enzyme activities; the more severe lesions showed the higher levels. These results provide indirect evidence to support increased cell turnover rather than maturation arrest in mitosis in the small intestinal epithelial cells in celiac disease.