Vitamin B12

Moderator: Dr. B.C. Koner

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

Structure

Different R groups

Different forms

•Cyano

•Methyl

•Adenosyl

•Hydroxo

•Aquo

Smokers should note that the cyanide absorbed from the smoke into the

blood causes the replacement of the 5'-deoxyadenosyl group by a cyanide.

Dietary source

• Present only in foods of animal origin

• That too is a product of microbial synthesis.

• Plants do not use B12.

Iran study fruit fertiliser

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.

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

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

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.

No transmembranedomain in cubilin

TranscobalaminesTCII:• 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.

B12-Dependent Enzymes

• Methylmalonyl CoA mutase(adenosyl cobalamin)

• Methionine synthase (methyl cobalamin)

• Leucine aminomutase

Leucine aminomutase

Folate trap