Inactivation of corticosteroids in intestinal mucosa by 11 beta-hydroxysteroid: NADP oxidoreductase (EC 1. 1. 1. 146)
Activity of the enzyme 11 beta-hydroxysteroid:NADP oxidoreductase (EC 1.1.1.146) in human intestinal mucosa was determined by incubating scraped mucosa with /sup 3/H-cortisone and /sup 14/C-cortisol; these steroids were then extracted, separated chromatographically, and the radioactivity assayed to determine simultaneously both reductase and dehydrogenase activities. This was the only significant metabolic alteration which the substrate underwent. Only two cases had slight (5 and 13%) reductase activity. In 35 patients, 16 male and 19 female, including seven cases of Crohn's disease, three ulcerative colitis, five diverticulitis, two undergoing surgery for repair of injuries and 18 for carcinoma of colon or rectum, cortisol was converted to cortisone in 15 min with a wide range of values distributed uniformly up to 85% dehydrogenation, with a mean of 42%. When tissue homogenates were fortified with coenzymes, excess NADPH lowered dehydrogenase activity 81%; excess NADP increased dehydrogenase activity 2-fold in three cases. It is possible that a value is characteristic of an individual but perhaps more likely enzyme activity varies with metabolic events involving changes in the coenzyme levels in mucosa, and a random sampling might be expected to yield such a distribution of values. In any event, where activity is high most of the cortisol is inactivated within minutes. It is suggested that synthetic corticoids which escape such metabolic alteration might, except during pregnancy, prove superior in the treatment of conditions such as inflammatory bowel disease.
- OSTI ID:
- 6848465
- Journal Information:
- Am. J. Gastroenterol.; (United States), Vol. 78:10
- Country of Publication:
- United States
- Language:
- English
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INACTIVATION
DIGESTIVE SYSTEM DISEASES
DIAGNOSTIC TECHNIQUES
HYDROCORTISONE
HYDROGENASES
BIOCHEMICAL REACTION KINETICS
INFLAMMATION
INTESTINES
MUCOUS MEMBRANES
OXIDOREDUCTASES
CARBON 14 COMPOUNDS
LABELLED COMPOUNDS
MAN
TISSUE CULTURES
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ADRENAL HORMONES
ANIMALS
BODY
CORTICOSTEROIDS
DIGESTIVE SYSTEM
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ENZYMES
GASTROINTESTINAL TRACT
GLUCOCORTICOIDS
HORMONES
HYDROXY COMPOUNDS
ISOTOPE APPLICATIONS
KETONES
KINETICS
MAMMALS
MEMBRANES
ORGANIC COMPOUNDS
ORGANS
PATHOLOGICAL CHANGES
PREGNANES
PRIMATES
REACTION KINETICS
STEROID HORMONES
STEROIDS
SYMPTOMS
VERTEBRATES
551001* - Physiological Systems- Tracer Techniques