Introduction to Enzyme and Coenzyme Chemistry - E-Library Home

280 Appendix 4
from water at a-position. Note that the same hydrogen transferred from
NADPH to FAD is then transferred to substrate.
(5) Formation of Xavin hydroperoxide intermediate from FADH 2 and O 2 .
Attack on Xavin hydroperoxide para to phenolic hydroxyl group, followed
by elimination of nitrite to give quinone. Quinone then reduced to hydroquinone
by second equivalent of NADH.
(6) Mechanism of hydroxylation as for general mechanism, via iron(IV)-oxo
species. Triple bond of inhibitor is epoxidised to give reactive alkene epoxide
intermediate, which rearranges with 1,2-shift of H to give a ketene
intermediate. This is attacked either by water, giving the by-product, or by
an active site nucleophile, leading to covalent modiWcation.
O
HN
O
N
H
H*
O 2 , Fe 2+
α-KG
HN
O
O
N
H
O
H*
HN
O
O *H
N
H
O
H 2 O
EnzX −
HN
O
HN
O
N
H
O
H
H
H*
XEnz
O
H*
CO 2 H
O
N
H
Chapter 7
(1) Opening of monosaccharide at C-1 reveals aldehyde substrate. Since
enzyme requires no cofactors it presumably proceeds through imine linkage
at C-2 of pyruvate, followed by deprotonation at C-3 to give enamine
intermediate. Carbon–carbon bond formation between enamine and aldehyde,
followed by hydrolysis of resulting imine linkage.
(2) Sequential addition of three malonyl CoA units as for fatty acid synthase
gives a tetraketide intermediate. Formation of carbanion between Wrst and
second ketone groups, followed by reaction with thioester terminus, leads
to formation of chalcone. Formation of carbanion adjacent to thioester
terminus, followed by reaction with Wrst ketone group, leads after decarboxylation
(b-keto-acid) to resveratrol. Very similar reactions, so similar
active sites, but diVerences in position of carbanion formation and carbon–
carbon bond formation.
(3) Attack of bicarbonate onto phosphate monoester gives enol intermediate
and carboxyphosphate. Attack of enol at C-3 onto carboxyphosphate gives
carboxylated product.