Absorption and Transport of Cobalamin (Vitamin B12)

Annual Reviewswww.annualreviews.org/aronline358 SEETHARAM & ALPERSC. Function of R ProteinsAnnu. Rev. Nutr. 1982.2:343-369. Downloaded from arjournals.annualreviews.orgby Hebrew University of Jerusalem on 11/18/08. For personal use only.The R proteins from saliva or gastric secretion do not appear to haveany role in the intestinal absorption of cobalamin, nor do the plasma R proteinsTC I and TC III facilitate cellular transport of eobalamin. First,the R-protein-[STCo]cbl complex does not bind to the ileal receptors.Second, two brothers who had deficiencies of all R proteins were hematologicallynormal (74). Some evidence suggests that binding of cblR proteins protects cobalamin from bacterial utilization. Lactoferrin, aniron binding protein with a well-described antibacterial action, has atissue distribution very similar to that of R proteins. Furthermore, highconcentrations of R proteins are present in granulocytes. Gilbert (60)and Gullberg (68, 69) have suggested that the R proteins may playa role in host defense against bacteria. Allen (2) has suggested a rolecleating the cbl analogs found in the intestinal lumen and in the tissues00~).D. Binding and Uptake of TC I-cbl and TC III-cblby Hepatic Asialoglycoprotein ReceptorAshwell & Morell (12) have shown that liver plasma membranes bindwide variety of plasma glycoproteins as the initial step in their removal fromplasma. These glycoproteins bind to this plasma receptor only if the terminalgalactose is intact and no sialic acid is present on the glycoprotein. Theasialoglycoproteins are internalized and degraded by the lysosomes within90 minutes. Some R proteins seem to be cleared by the receptor-mediatedsystem. Using the rabbit, Burger et al (21) have shown that [125I]humangranulocyte R-[STCo]cbl and [J25I]human TC III[57Co]cbl are cleared rapidly(Tw=5 min) from plasma, whereas [1251] human TC I-[57Co]cbl and[131I] bovine serum albumin have prolonged plasma survival. The faster rateof clearance of R-cbl and TC III-cbl can be prolonged by saturating the liverplasma membrane receptor by a prior injection of desialated fetuin. Moreover,the TC I-cbl complex can be cleared more rapidly by desialating itbefore injection. The physiological significance of asialoglycoprotein receptorin clearing R-cbl from plasma is not fully known. Allen (2) indicates thatthis mechanism may help in the clearance of cbl analogs that might beformed by bacteria, especially since R proteins are known to bind tightlya wide variety of cbl analogs (8, 62). Analogs will then be secreted into bileafter removal by the liver. Reabsorption of the analogs will be poor sinceIF binds analogs of cobalamin with a lower affinity than cobalamin itself(18). It is interesting to note that in studies involving two brothers (25)