Sequestration of crystalline and endogenous cobalamin by R binders down to the distal ileum in exocrine pancreatic dysfunction.
It has been recently shown that crystalline cyanocobalamin in exocrine pancreatic insufficiency is sequestered by R binders down to the proximal jejunum, and that bile inhibits the binding of cobalamin to intrinsic factor. In freshly collected human bile, we have found a single type of apo R binder, with a relative molecular mass of 128 100, a molecular radius of 4.65 nm, and a mean isoelectric point of 3.72. Salivary and biliary holo R binders were incubated with normal human gastric juice and intestinal juice from healthy subjects and patients having exocrine pancreatic insufficiency. No degradation of these two holo R binders occurs with normal gastric juice and intestinal juice from patients after four hours incubation time at 37 degrees C, but a partial degradation of salivary holo R binders and a complete loss of biliary Cbl binding capacity were observed with normal intestinal juice in the same in vitro conditions. We have confirmed in vivo, using a triple-lumened tube, that a part of the salivary and biliary holo R binders remains undegraded down to the distal ileum in two patients with exocrine pancreatic insufficiency. These findings strongly suggest that the enterohepatic circulation of cobalamin is effective in healthy subjects, whereas it is partially interrupted in the patients. They provide a proof that a part of endogenous and crystalline exogenous cobalamin is sequestered to R binders down to the distal ileum, and confirm that the failure to degrade the digestive R binders is responsible for the malabsorption of crystalline cobalamin in exocrine pancreatic dysfunction.
D001646:Bile / Q000032:analysis; D001826:Body Fluids / Q000378:metabolism; D006801:Humans; D007082:Ileum / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism; D010179:Pancreas / Q000503:physiopathology; D010182:Pancreatic Diseases / Q000378:metabolism*; D014155:Transcobalamins; D014805:Vitamin B 12 / Q000032:analysis*
D014155:Transcobalamins; D014805:Vitamin B 12