8 Structure-Function Relationship of Vitamin B Coenzyme (Adenosylcobalamin) in the Diol-Dehydrase System Downloaded by UNIV OF ARIZONA on March 28, 2017 | http://pubs.acs.org Publication Date: December 10, 1980 | doi: 10.1021/ba-1980-0191.ch008
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TETSUO TORAYA and SABURO FUKUI Laboratory of Industrial Biochemistry, Department of Industrial Chemistry, Faculty of Engineering, Kyoto University, Sakyo-Ku, Kyoto 606, Japan.
The structure-function relationship of vitamin B coen zyme (adenosylcobalamin) was investigated with diol dehydrase through the use of a number of analogs of the coenzyme to gain information concerning the mechanism of cleavage of the C-Co bond of the coenzyme by the apoprotein. Modifications were introduced to the corrin ring or its amide sidechains, the Coα (lower) nucleotide ligand, or the Coß (upper) nucleoside ligand. It was suggested strongly that interactions between enzyme and coenzyme at the adenosyl portion as well as at the peripheral amide sidechains of the corrin ring play essential roles in activation of the C-Co bond of the coenzyme. Some aspects of enzyme-coenzyme interactions also were studied by the affinity chromatography technique using several corrinoid derivatives immobilized on agarose gel through various positions of the molecule. 12
A
denosylcobalamin (vitamin B coenzyme) is a corrinoid compound that is distributed widely in living organisms. This coenzyme, first discovered by Barker and co-workers in 1958 (I, 2), is not only the most complicated nonpolymer organic compound of known structure (Figure 1), but also the first known naturally occurring organometallic compound containing a stable C - C o sigma bond. The coenzyme is known to participate as coenzyme in the ten enzymatic rearrange1 2
0-8412-0514-0/80/33-191-139$05.00/0 © 1980 American Chemical Society
Dolphin et al.; Biomimetic Chemistry Advances in Chemistry; American Chemical Society: Washington, DC, 1980.
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140
BIOMIMETIC CHEMISTRY
NH
2
Figure 1. Structure of vitamin B coenzyme (adenosylcobalamin): L — adenosyl group 12
merit and reduction reactions (Table I). The unifying feature of the seemingly quite different chemical reactions catalyzed by adenosylcobalamin-requiring enzymes is that the coenzyme serves as an intermediate carrier for a hydrogen transfer. It is accepted that an early event in all of these reactions is the cleavage of the C - C o bond of the coenzyme, which leads to generation of the catalytic center. How does the enzyme catalyze this cleavage? This is one of the most important and interesting questions for biochemists and chemists in this field. To answer this question, the structure-function relationship of adenosylcobalamin was studied in detail with diol dehydrase (DL1,2-propanediol hydro-lyase, E C 4.2.1.28), one of the representative B enzymes, through the use of a number of analogs of the coenzyme. Some aspects of the enzyme-coenzyme interaction were investigated 1 2
Dolphin et al.; Biomimetic Chemistry Advances in Chemistry; American Chemical Society: Washington, DC, 1980.
Dolphin et al.; Biomimetic Chemistry Advances in Chemistry; American Chemical Society: Washington, DC, 1980.
2
H
HOOC—C—CH —
H
Carbon-Carbon Rond Cleavage
I
CH 3
I
3
II
2
3
II
CH
2
F± H O O C — C H — C — C O O H
CH
O
HOOC—CH—C—SCoA
CH
NH
HOOC—CH—CH—COOH
Reaction
a-Methyleneglutarate mutase
Methylmalonyl-CoA mutase
Glutamate mutase
Enzyme
Table I. Enzymatic Reactions in Which Adenosylcorrinoids Are Involved as Coenzyme
Downloaded by UNIV OF ARIZONA on March 28, 2017 | http://pubs.acs.org Publication Date: December 10, 1980 | doi: 10.1021/ba-1980-0191.ch008
Dolphin et al.; Biomimetic Chemistry Advances in Chemistry; American Chemical Society: Washington, DC, 1980.
H
IH
2
2
2
3
2
2
2
3
R C H C H O + H 0 (R = C H , H , C H O H )
OH
3
10
H
|/| C
Base
(PPP = P O *-)
1
|\| c
2
lOHl H PPP—CH
2
+ R(SH) -
2
OH
H^
C^H
PPP—CH
H
C
H
H)C
Base + R—S, + H , 0
R — C H — C — O H ^ R C H C H O + H 0 (R = C H O H , C H , H)
OH
R—CH—C—OH
H
Carbon-Oxygen Rond Cleavage
Reaction
Table I. Continued
Downloaded by UNIV OF ARIZONA on March 28, 2017 | http://pubs.acs.org Publication Date: December 10, 1980 | doi: 10.1021/ba-1980-0191.ch008
Ribonucleotide reductase
Glycerol dehydrase
Diol dehydrase
Enzyme
TORAYA AND F U K U l
Vitamin B Coenzyme
2 S
G
Downloaded by UNIV OF ARIZONA on March 28, 2017 | http://pubs.acs.org Publication Date: December 10, 1980 | doi: 10.1021/ba-1980-0191.ch008
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