Organic Chemistry

Section 25.6 Pyridoxal Phosphate: Vitamin B 6 1057

In the first step of transamination, a proton is removed from the of the amino
acid bound to PLP. Rearrangement of the electrons and protonation of the carbon
attached to the pyridine ring, followed by hydrolysis of the imine, forms the acid
and pyridoxamine. At this point, the amino group has been removed from the amino acid,
but pyridoxamine has to be converted back to enzyme-bound PLP before another round
of catalysis can occur. Pyridoxamine forms an imine with the second
substrate of the reaction. Removal of a proton from the carbon attached to the pyridine
ring, followed by rearrangement of the electrons and donation of a proton to the
of the substrate forms an imine that, when transiminated with a lysine side
chain, releases glutamate and reforms enzyme-bound PLP.
Notice that the proton transfer steps are reversed in the two phases of the reaction.
Transfer of the amino group of the amino acid to pyridoxal requires removal of the
proton from the and donation of a proton to the carbon bonded to the pyri-
dine ring. Transfer of the amino group of pyridoxamine to requires re-
moval of the proton from the carbon bonded to the pyridine ring and donation of a
proton to the a-carbon.

a-ketoglutarate

a-carbon

a-carbon

a-ketoglutarate,

a-keto

a-carbon

H

R CCO− B H

B −

B −

B −

mechanism for PLP-catalyzed transamination of an amino acid

transaminated

amino acid

an -keto acid

+N

H

N

HC

RCCO−

O

RCCO−

O

+ RCCO−

O

O

−OCCH 2 CH 2 CCO−

O

O

O

O

H

O

+N

H

+N

H

H 2 C

CH 3

PiO

H

O

CH 3 N CH 3 CH 3

H

N

HC H

O

N

H 2 C H

O H 2 O

NH 2

PiO PiO PiO

pyridoxamine

-ketoglutarate

B H

transimination

with E (CH 2 ) 4 NH 2

−OCCH 2 CH 2 CHCO−

O

+NH 3

O

−OCCH 2 CH 2 CHCO−

CH 3

PiO

O O

CH 3 CH 3

CH 3

H 2 O

PiO

PiOPiO

N

H

N

HC H

O

N

HC H

O

(CH 2 ) 4

E

−OCCH 2 CH 2 CCO−

O O

N

H

H N

H C

B−

H

O

−OCCH 2 CH 2 CCO−

O O

N

H

N

HC H

O

+

+

+

N

H

+

+

glutamate