The metabolism of cobalamin bound to transcobalamin II and to glycoproteins that bind Cbl in HepG2 cells (human hepatoma).
The binding, internalization, processing and release of labeled cyanocobalamin (CN[57Co]Cbl) bound to human transcobalamin II (TC II) were studied in HepG2 cells, a line of hepatocytes derived from a human hepatoma. The cells bound the TC II-Cbl by specific, high affinity receptors. Within the cell, the CN-Cbl was promptly freed from TC II and the CN-Cbl converted to more active forms including adenosyl Cbl (AdoCbl) and methyl Cbl (MeCbl). Whereas free labeled Cbl was still present at 72 hours after entry, the cells also bound Cbl to an intracellular binder (ICB) presumed to represent the holo enzymes dependent on Cbl. At levels of TC II that saturated the receptors for TC II-Cbl, much of the Cbl entering the cells remained free and was converted to AdoCbl. Under these circumstances the cells released free Cbl, mostly AdoCbl. Human R type binders of Cbl, which are glycoproteins and some having a terminal galactose, were bound by the HepG2 cells. The binding was characteristic of the receptor system responsive to a terminal galactose, or asialoglycoproteins, but was inconsistent and of low affinity. Cbl bound to R binder was internalized and converted to coenzyme forms of Cbl, but the process was much less effective than when the Cbl entered via the TC II receptor system. It was concluded that the receptors for R-Cbl were unlikely to contribute to the physiologic transport of Cbl in man, but may function in some yet unknown way.
D037263:Asialoglycoprotein Receptor; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D002460:Cell Line; D003037:Cobalt Radioisotopes / Q000378:metabolism; D003038:Cobamides / Q000378:metabolism; D005690:Galactose / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism; D013997:Time Factors; D014155:Transcobalamins / Q000378:metabolism*; D014805:Vitamin B 12 / Q000031:analogs & derivatives / Q000378:metabolism*
D037263:Asialoglycoprotein Receptor; D003037:Cobalt Radioisotopes; D003038:Cobamides; D006023:Glycoproteins; D011971:Receptors, Immunologic; D014155:Transcobalamins; C019476:mecobalamin; C000913:cobamamide; D014805:Vitamin B 12; D005690:Galactose