RAPID POSTABSORPTIVE METABOLISM OF NICOTINIC-ACID IN RAT SMALL-INTESTINE MAY AFFECT TRANSPORT BY METABOLIC TRAPPING

Postabsorptive metabolism of [H-3]nicotinic acid by rat proximal jejun um was studied in vitro using the everted sac technique and in vivo by applying ligated loops. Metabolites were analyzed by HPLC with radioc hemical detection. Within 60 min of incubation nicotinic acid was almo st completely metabolized in vivo. Only 3.2% of the label could be det ected in the original substrate nicotinic acid, whereas >90% of the ra dioactivity present in the gut wall was nicotinamide. Further in vitro experiments revealed that conversion was rapid; after 10 min of incub ation >40% of the substrate was converted to other metabolites. From a nalysis of the serosal fluid, it was evident that only nicotinic acid and nicotinamide were transferred to the serosal compartment. Rapid co nversion of nicotinic acid might affect the transport step itself by m etabolic trapping, resulting in the maintenance of a substrate gradien t necessary for passive absorption. In contrast, as examined by gradie nt centrifugation, the substrate in subcellular organelles is transfer red only to a minor extent.