Organic Chemistry

Section 25.7 Coenzyme B 12 :Vitamin B 12 1063

In each of these coenzyme –requiring reactions, a group (Y) bonded to one
carbon changes places with a hydrogen bonded to an adjacent carbon.

For example, glutamate mutase and methylmalonyl-CoA mutase both catalyze a reac-
tion in which the group bonded to one carbon changes places with a hydrogen
of an adjacent methyl group. In the reaction catalyzed by dioldehydrase, an OH group
changes places with a methylene hydrogen. The resulting product is a hydrate that
loses water to form propanal.

Mechanism for Coenzyme
The chemistry of coenzyme takes place at the bond joining the cobalt and the
group. The currently accepted mechanism for dioldehydrase in-
volves an initial homolytic cleavage of this unusually weak bond (26 kcal mol or
109 kJ mol, compared with 99 kcal mol or 414 kJ mol for a bond). Breaking
the bond forms a radical and reduces Co(III) to Co(II). The
radical abstracts a hydrogen atom from the C-1 carbon of the
substrate, thereby becoming A hydroxyl radical ( ) migrates
from C-2 to C-1, creating a radical at C-2. This radical abstracts a hydrogen atom
from forming the rearranged product and regenerating the
radical that recombines with Co(II) to regenerate the coenzyme.
The enzyme–coenzyme complex is then ready for another catalytic cycle. The initial
product is a hydrate that loses water to form propanal, the final product of the reaction.

It is likely that all coenzyme –requiring enzymes catalyze reactions by means of
the same general mechanism. The role of the coenzyme is to provide a way to remove
a hydrogen atom from the substrate. Once the hydrogen atom has been removed, an
adjacent group can migrate to take its place. The coenzyme then gives back the
hydrogen atom, delivering it to the carbon that lost the migrating group.

B 12

5 ¿-deoxyadenosyl

5 ¿-deoxyadenosine,

Oª

5 ¿-deoxyadenosine. H

5 ¿-deoxyadenosyl

5 ¿-deoxyadenosyl

> > > C¬H

>

5 ¿-deoxyadenosyl

B 12

B 12

COO-

Y H

a coenzyme B 12 -

requiring enzyme

CC

H Y

CC

B 12

OH OH

a hydrate

dioldehydrase

CH 3 CHCH 2 OH CH 3 CH 2 CHOH

−H 2 O

O

coenzyme B CH^3 CH^2 CH

12

1,2-propanediol propanal

OH

HO

CH 3

C H

HC

Ad CH 2

Co(III)

H

OH

HO

CH 3

C H

HC

Ad CH 2

Co(II)

H

OH

HO

CH 3

C H

C

Ad CH 3

Co(II)

H

OH+ 2 O

CH 3

H C H

C

Ad CH 2

Co(III)

H

OH

HO

CH 3

H C H

C

Ad CH 2

Co(II)

H

OH

HO

CH 3

C H

C

Ad CH 2

Co(II)

H

the role of 5 ́-deoxyadenosylcobalamin in a coenzyme B 12 -requiring enzyme-catalyzed reaction

H

propanal a hydrate

3-D Molecule:

Coenzyme B 12

Coenzyme is required by enzymes

that catalyze the exchange of a

hydrogen bonded to one carbon with a

group bonded to an adjacent carbon.

B 12