2. Facts
• Only water soluble vitamin that is stored
• Synthesized exclusively by microbes
• Dietary source is exclusively of animal origin
• Rare compound with direct metal-carbon
bond
10. Absorption
• Peptic digestion releases dietary vitamin B12, which then binds
to salivary B12-binding proteins called Haptocorrins, or R
binders.
• R-B12 complexes are transported to the duodenum and
processed by pancreatic proteases; this releases B12, which
attaches to intrinsic factor secreted from the parietal cells of
the gastric fundic mucosa.
• The intrinsic factor-B12 complex passes to the distal ileum and
attaches to the epithelial intrinsic factor receptors, which
leads to absorption of vitamin B12.
• The absorbed B12 is bound to transport proteins called
transcobalamins, which then deliver it to the liver and other
cells of the body.
11. Haptocorrin
• R-binder/cobalophilins/Transcobalamin-I
• encoded by the TCN1 gene
• produced by the salivary glands and the parietal cells in the
stomach.
• Function: Protection of the acid-sensitive vitamin B12 while it
moves through the stomach.
• Enterohepatic circulation
12. Intrinsic Factor of castle
• Glycoprotein secreted by parietal cell of stomach in the region
of fundus and body
• optimum pH for action – 7
• Secretion of IF is stimulated by food, histamine and gastrin;
inhibited by vagal block.
• After digestion of haptocorrin by pancreatic enzymes, binds to
B12 in small intestine in 1:1 ratio.
• Complex itself is endocytosed by IF receptors in ileum
13. Cubam
• Cubam, is the multi-ligand receptor located in the terminal
ileum, specializing in absorption of vitamin B12.
• Cubam is made up of amnionless (AMN), and cubilin
• Cubilin is the receptor, whereas amnionless is involved in the
receptor mediated endocytosis of the complex.
15. Transcobalamines
TCII:
• The physiologically active form is TCII , a beta globulin synthesized
mainly by liver
• 1:1 ratio
• The complex then binds to specific surface receptors on developing
blood cells in the bone marrow. Vitamin B12 is then released by
hydrolysis. The TCII is not reutilized.
• The plasma half-life of TCII is 12 hours and congenital absence of it
causes megaloblastic anaemia within weeks of birth.
TC I and III (cobalophillins):
• -globulins synthesized by granulocytes and known as R-binders
that are found in a wide range of body fluids. TCI&III do not readily
release vitamin B12 to the developing tissues.
• The plasma half-life is 9-12 days and congenital absence of them
causes no physiological impairment. It is postulated that
cobalophillins aid in host defencse against bacteria by depriving
them of B12.
Difference:
1. Cobalamin contains a corrin ring system that differs from the porphyrins
in that two of the pyrrole rings are linked directly rather than
through a methene bridge.
2. it is not planar
Cyanocobalamin form of B12 does not occur in nature normally
By-product of the fact that other forms of B12 are avid binders of cyanide (-CN) which they pick up in the process of activated charcoal purification of the vitamin after it is made by bacteria in the commercial process.
easy to crystallize and is not sensitive to air-oxidation, it is typically used as a form of B12 for food additives and in many common multivitamins.
Pure cyanocobalamin possesses the deep pink color associated with most octahedral cobalt(II) complexes and the crystals are well formed and easily grown up to millimeter size.
Megalin is a cell-surface receptor/transporter consisting of a large extracellular region, a single transmembrane domain, and a C-terminal cytoplasmic tail. The extracellular domain of megalin contains four clusters of lipoprotein receptor ligand-binding repeats (blue), growth factor repeats, an EGF repeat, and YWTDspacer regions. The second cluster of ligand-binding repeats has been identified as a common binding site for several ligands including apolipoprotein E (Apo E), apolipoprotein M (Apo M), retinol binding protein (Rbp), and transthyretin (Ttr). Megalin also binds the soluble form of the folate receptor (Folr1), and the morphogen sonic hedgehog (Shh). The cytoplasmic tail of megalin binds Dab2, a cytosolic adapter protein important for megalin-mediated endocytosis, and Dab2 binds and recruits Myo6 to clathrin-coated vesicles. The receptor-associated protein (Lrpap1; RAP) binds both megalin and cubilin. Cubilin is a peripheral membrane receptor comprised of a short amino terminal, eight EGF type domains, and 27 CUB domains (green). The amino-terminal end of cubilin is attached to the extracellular part of amnionless (Amn), and amnionless provides the transmembrane domain necessary for the anchoring and endocytic trafficking of cubilin. Cubilin ligands include transferring (Trf), albumin, hemoglobin, apolipoprotein A1 (ApoA1), and intrinsic factor (IF)-vitamin B12.
Why it is known as amnionless – defect is associated with amnionless gastrulation in rodents
Hepatocytes take up Cbl or its analogues (CblAs) bound to HC via the asialoglycoprotein receptor (ASGP-R) and Cbl bound to TC II via TC II-R. Cbl liberated following degradation of HC–Cbl or TC II–Cbl is either stored in the form of Cbl-dependent enzymes or secreted via bile to be reabsorbed. CblA either released from HC or still bound to it is secreted via bile. HC in the bile might originate from the circulation (via uptake by the hepatocytes) or from de novo synthesis by the liver. In either case it is degraded in the intestinal lumen by pancreatic proteases. Once in the lumen, the secreted Cbl and CblA bind to gastric IF and, depending upon the availability of free IF–Cbl binding sites of cubilin, are either reabsorbed as a part of the enterohepatic circulation or excreted in the faeces. The three receptors are shown in their monomeric forms, although cubilin and TC II-R are known to exist as a trimer and dimer, respectively; only one of the two subunits of ASGP-R is shown