Gastric intrinsic factor and its receptor.
Cbl metabolism has been the subject of many studies since the existence of Cbl was suspected in the first decades of the twentieth century. These studies have confirmed the high complexity of the assimilation of Cbl by the organism. During absorption, Cbl is bound to two glycoproteins, Hc and IF, in a consecutive manner. Over the last few years, it has been demonstrated that Cbl bound to Hc in the stomach is only transferred to IF after the action of pancreatic trypsin. It is also possible that Hc-bound biliary Cbl is transferred to IF in this way and that the Cbl in the Cbl-IF complex is absorbed in the terminal ileum, thus constituting an enterohepatic cycle. Knowledge concerning the sites of synthesis and secretion of IF is becoming more detailed due to the use of immunocytochemistry and in situ hybridization techniques. It is now certain that in man, IF is not only localized in gastric parietal cells, but also in other foregut-derived cells. This observation may explain the multiple physiological stimuli involved in mediating IF secretion. Determination of the molecular structure of purified Cbl binders can be added to the significant progress made due to the application of molecular biology techniques to the field of isolation and structural characterization of cDNA encoding Cbl binders, and particularly IF. Studies of IF, Hc and TC in different species and those into the properties of acceptor fragments have allowed the distinction between the Cbl binding site on IF and the IF-Cbl binding site on the IFCR. The absence of experimental models cause difficulties in studying transcytosis of Cbl through the enterocyte. There are also problems in determining the structure of IFCR as it is difficult to obtain a large quantity of a molecule which denatures very quickly. Studies into IFCR expression in polarized cancerous cells of intestinal or renal origin, including the effects of different pharmacological agents, along with the results of immunochemical investigations are beginning to clarify the pathway involved in the transport of Cbl through the enterocyte.
Service du Laboratoire de Biochimie A. Hôpital de Brabois, Vandoeuvre, France.
J P
JP
Nicolas
J L
JL
Guéant
D000328:Adult; D000818:Animals; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism*; D006801:Humans; D007437:Intrinsic Factor / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D008297:Male; D018000:Receptors, Peptide / Q000378:metabolism*
D018000:Receptors, Peptide; C028199:intrinsic factor receptor; D007437:Intrinsic Factor