UBC Theses and Dissertations
The carnitine and carnitine ester content of rat bile and human duodenal fluid Hamilton, Jennifer Jane
Carnitine is necessary for the beta-oxidation of long-chain fatty acids. Carnitine esters are produced to transport fatty acids across the otherwise impermeable inner mitochondrial membrane. Although carnitine has been investigated in many tissues, the content and possible roles of carnitine in the gastrointestinal tract have not been completely investigated. The kinetics of carnitine absorption have been determined but the treatment and sources of carnitine in the intestinal tract are unknown. This study investigated the possible contribution of bile to the carnitine content of the intestinal lumen. First, the amounts of carnitine and carnitine esters in rat bile were measured. Then, the origin of carnitine in the bile was studied. Finally, the carnitine content of human bile-rich duodenal fluid was investigated. Bile was collected from eleven anaesthetized (pentobarbital) adult male rats. Bile flow was measured gravimetrically and carnitine and its esters were determined using a radiochemical carnitine assay. Specific types of carnitine esters were quantitated after first extracting the samples with chloroform and methanol. The origin of carnitine in the bile was investigated indirectly by measuring the carnitine content of bile from rats who were fasted for 72 hours or orally administered with tetradecylglycidic acid, an inhibitor of carnitine palmitoyltransferase I. These treatments differently affect the amounts and types of carnitine esters found in the liver and extrahepatically. The bile carnitine was compared to the serum and liver carnitine after these treatments to see if similarities existed. The origin of carnitine in the bile was further studied by administering [¹⁴C]carnitine intravenously and determining its recovery in the bile. Human bile-rich duodenal fluid was collected from ten patients with suspected cholelithiasis by duodenal aspiration using nasogastric intubation after pancreozymin-cholecystokinin injection. Large quantities of total carnitine and long-chain carnitine esters were found in rat bile relative to other tissues. It appears that carnitine enters the bile both directly from the newly synthesized or stored hepatic carnitine pool and also following hepatic uptake of carnitine from serum. The latter is first esterified in the liver before entering the bile. The types and amounts of carnitine esters in the bile, thus, appear to reflect the metabolic state at the time of bile formation. Carnitine was also found in human bile-rich duodenal fluid. The percentage of long-chain carnitine esters was similar to that found in rat bile. The discovery of carnitine in rat bile challenges the common assumption that only dietary carnitine is present in the intestinal tract. It also disputes the theory that urine is the sole route for carnitine excretion. In addition, it suggests that carnitine depletion could result if carnitine in the bile is not reabsorbed in the intestine. This might occur with general malabsorption syndromes.
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