Vitamin b12

Structure of Vit.b12 of Vit.b12

• It contains 4 pyrrol rings• Co is present in the centre with a

cordination no. 6• 4 N of pyrol ring are attached by

coordinate linkage• 2 pyrol rings 1 & 4 are directly joined

rather than methane bridge• In 1st posn. It is attached by Dimethyl

benziamide ribonucleotide

• Ribonucleotide molecule in turn is connected to propionic side chain of 4th ring of pyrol through aminoisopropanol.

• R groups is attached at 6th posn• Different R groups give different

type---- a) R=CN- cyanocobalin b) R=OH- hydroxycobalmin c) R=CH3-methylcobalmin d) R=Cl – chlorocobalmin e) R=5’deoxyadenosyl-5 adenosyl cobalmin

Structure of vit. b12

Sources

• Exogenous – liver ,egg, milk, kidney, curd

• Endogenous – intestinal bacteria

Daily requirements

Adults - 3µg/day

Preg. N lactation -4µg/dayChildren-0.5-1.5µg/day

Absorption , transport and excretion of Vit . b12

• Vit.b12 is absorbed from ileum • It is mediated by receptor sites in

ileum.• It requires a.)HCl b)intrinsic

factorIntrinsic factor is a glycoprotein secreted by the

parietal cells of gastric mucosa and carries vit.B12 for absorption in the ileum.

Mechanism of absorption

• In the intestine , Vit B12 binds to cobalphilin , a protein secreted in the saliva

• In the duodenum cobalphilin is hydrolyzed releasing vit for binding to the intrinsic factor

• I.F. binds to B12 for transport through intestinal lumen to absorptive site of ileum

• In the ileum I.F. is attached to specific binding site as a result B12 is removed from I.F. in the presence of calcium ions and releasing the factor secreted by the duodenum.

• B12 now enters the ileal mucosal cells for absorption into duodenum.

• Small amounts 1-3% may be absorbed by diffusion

• About 0.5-10µg of B12 is transported after absorption.

• After absorption Vit B12 is transported to various tissues in combination with plasma protein transcobalmin 2

• It is stored in liver bound to transcobalmin 1

• After transport in the blood free cobalmin is released in the cytosol cells as hydroxycobalmin B12 which is converted to

• A) METHYLCOBALMIN in cytosol or• B) DEADENOSINE COBALMIN B12 in mitochondria• Methylcobalmin is taken up by liver and is

converted to deadenosyl B12 where it is stored.

• B12 is mainly excreted through bile • About 20-25µg/day is excreted in urine

Synthesis of methionine from homocystein

Homocystein

N5 methyl THF

THF

methionine

METHYLCOBALMIN

FOLATE TRAPB12 is necessary for conversion of

N5 methyl THF to THF to form methylcobalminB12 which is

required for conversion of homocystein to methionine.

In B 12 defeciency the above reaction does not take place and folate is permanently trapped as

N5 methyl TH4 resulting in the non availabilty of TH4 required for 1C metabolism which is required for

the synthesis of purines, pyramidines n nucleic acid.this

process is called folate trap.

This leads to decrease in folic acid resulting in

Megaloblastic anemia

SYNTHESIS OF SUCCINYL COA FROM METHHYL MELONIN COA

• Deadenosine B12 is the coenzyme required in the conversion of methyl melonine coA to succinyl coA

• In B12 def. methly melonic acid accumulates and is excreted in urine therefore it is a sensitive index of B 12 def.

Other functions of vit.B12

• Formation of RBC beyond megaloblastic stage

• Conversion of ribonucleotides to deoxy ribonucleotides

• Maintaince sulphahydryl group in reduced state.

• It’s def. produces reduction of glutathione in blood.

• In bacteria , acts coenzyme in conversion of glutamate or aspartate.

Defeciency of vit.B12

Megaloblastic anemia

• It is due to def. of folic acid/B12

• Cell division is sluggish but cytoplasmic development is normal

• ratio of RNA/DNA

• Nucleolated RBC’s are seen.

demyleination

• In B12 def. due to non availabilty of active methionine , methylation of phospatidyl ethanolamine to phosphatidyl choline is not adequate so ethanolamine is not adequately converted to choline in the absence of B12

• It leads to def. of myelin sheath around nerves.

Pancreatic insufficiencyIt results in excretion

of cobalophilin

Pernicious anemia

• Type of megaloblastic anemia due to def. of INTRINSIC FACTOR resulting in the failure of abs. of vit.B12

• It is thought that pernicious anemia is caused by autoimmune reaction against gastric parietal cells