Vitamin B12 coenzyme

BY
Dr. Prabhakara M.C.
Assistant Professor
Sir. M.V. Govt. Science College
Bhadaravathi, KARNATAKA-INDIA
 Vitamin B12 .

• Vitamin B12 (or B12 for short) is cyanocobalamin.

• There are many derivatives of cobalamins , B12a, B12o,
B12r, depending upon the substituent at 6th site on Co(III)
ion.

• The term B12 is used to refer to only one of these forms,

cyanocobalamin, which is the principal B12 form used
for foods and in nutritional supplements.
• Used for treating pernicious anemia.
 Vit.B12.
• A
 Structure - Corrin Ring system
• It contains a corrin ring
instead of porphyrin ring.
• Corrin ring system differs
from porphyrin.
• One =CH – linkage between
A & D pyrrole rings is
missing in corrin.
• Only 12 π elctrons
• No extensive π elctron
delocalization.
 Substituents on the ring
• The substituents are different than those of the porphyrin
ring.

• Positions 2, 7 & 18 bear acetamide, - CH2 –CONH2.

• Positions 3, 8 & 13 have propionamide, - CH2 -CH2 –CONH2

• At C-17, substituted propionamide present.

• The subsituent is a isopropyl group connected to

unusual ribnucleotide which has 5,6- dimethyl
benzimidazole.

• This benzimidazole is linked to 5th site of Co.

• 6th ligand is one of several groups like, -OH, -CN,
• - CH3, etc.

• In Vit.B12, the 6th ligand is –CN-, so Vit.B12 is

cyanocobalamin.

• In Vit. B12 coenzyme, it is 5’- adenosyl group. So the

Vit. B12 coenzyme is adenosyl cobalamin.

• The Co is in the plane of the corrin ring.

• The Co is capable of undergoing +1, +2 & +3 oxidation
states.

• For example, hydroxol cobalamin (R= CH3) contains

Co(III), Methyladenosyl contain cobalt (I).

• Vit.B12 coenzyme & methyl cobalamin are the only

enzymes containing a metal – carbon (M – C) bond.
Structural units of Vit.B12 coenzyme
Cobalamin (Vit.B12)
 Reactions catalyzed by CobalaminCoA

• Vit.B12 coenzyme acta as a prosthetic group for many

enzymes; catalyses many important biological reactions.

• Some B12 dependant enzymes:

• Glutamate mutase, diol dehydrase, methionine synthase,

methyl transferase, ribonucleotide reductase,
homosysteine transmethylase etc
• 1.Catalyses intramolecular rearrangements.

•e.g.: methyl malonyl Co A -  succinyl CoA.

 Conversion of Methyl malonyl CoA to Succinyl CoA

• This conversion is important as Succinyl CoA is involved

in biosynthesis of porphyrin for cyt, Hb, Mb etc.
• Thus, cobalamin (B12CoA ) deficiency is cause for
pernicious anemia.
 Glutamic acid to methyl aspartic acid

• This conversion glutamic acid to methyl aspartic acid is

an important reaction. Gutamate mutase enzyme needs
Vit.B12 coenzyme.
• Reaction occurs through 1,2- shift.
 Vicinal diols to aldehydes

• 3. Conversion of vicinal diols to their corresponding

aldehydes by means of diol -dehydrase reaction
 Transmethylation

• Transfer of methyl group (transmethylation) in

certain methylation reactions.

• The Co(III) can be alkylated & methylated [Co(III)- CH3] ;

these groups can the be transferred.

• e.g. conversion of homocysteine to methionine,

biosynthesis of choline, thymin etc.
Biosynthsis of methionine from homocysteine

The homocysteine transmethylase enzyme is vit.B12

CoA dependant.
 Other reactions
• Other reactions carried out by vitamin B12 are…
– Reduction of ribonucleotides to deoxy
ribonucleotides.

– Ribonuclotide reductase (RR) catalyses the

conversion of Ribonuclotides to Deoxy
ribonuclotides.
– This is the First step in DNA synthesis. It needs
B12 CoA as cofactor for its activity.
 Other reactions

– Reduction of disulfide to sulfhydrly group.

– Activation of amino acid for protein biosynthesis.

– Conversion of β methyl aspartic acid to glutamic

acid.

– Reduction of formate to methyl group.