Celiac-sprue Syndrome: Etiologic Considerations

Abstract

Gamma-glutamyl transpeptidase (γGTP), an intestinal mucosal enzyme, hydrolyzes γ glutamic carboxyl amide bonds. Subfractions of gluten were obtained by a modification of the hydrolytic scheme of Frazer. A high glutamic acid concentration characterizes gluten (38%) with enrichment of this amino acid in the residue following hydrolysis (68–72%). A γ-carboxyl peptide configuration appears in 2 of the subfractions. An in vitro assay syste utilizing the concept of enzyme inhibition showed the specific hydrolytic action of γGTP to be the γ-glutamic acid site in gluten and its subfractions. When γ-glutamyl beta naphtylamine served as substrate, with guinea pig intestinal mucosal scrapings supplying the enzyme, several of the subfractions acted as potential inhibitor compounds.Intestinal γGTP was determined in jejunal biopsies from 10 adult human subjects, 4 controls and 6 patients with small intestinal pathology including 4 with celiacsprue. Enzyme activity was found to be approximately half that of the normal in 2 sprue patients in clinical remission (normal fecal fat balance, normal morphological appearance of the jejunal biopsy and normal intestinal maltase activity). In the other 2 sprue patients the subjects were not in remission and the γGTP levels were even lower. These preliminary data suggest γGTP may be required to hydrolyze the γ glutamyl moieties in gluten and that a deficiency of this enzyme may result in the clinical entity of celiac-sprue. Whether there is a genetic-molecular basis for celiac-sprue, an acquired deficiency of enzyme, or both, will be answered when additional data become available.