Biomedical Engineering Reference
In-Depth Information
O
OH
NH
2
+
N
O
OH
H
HNE
Michael addition
Histidine
O
-
O
OH
O
O
H
+
OH
NH
2
+
NH
2
N
+
N
O
NH
O
H
NH
H
Michael adduct (enol)
Michael adduct (keto)
Nucleophilic addition
-
O
HO
O
O
H
+
OH
OH
O
O
NH
2
NH
2
+N
+N
H
H
Histidine 1,
N
-2-propane adduct
FIGURE 7.21 Formation of a 1,N-2-propane adduct of histidine following
reaction of 4-hydroxynonenol (HNE) with histidine. HNE reacts with histidine
via Michael addition to form an enol adduct, which subsequently tautomerizes
and undergoes a nucleophilic addition to form a stable adduct.
DNAOxidation Exposure of DNA to highly reactive hydroxyl radicals
can yield several products, depending where the oxidation occurs,
which can accumulate and may contribute to teratological outcomes.
Approximately 20 forms of oxidatively damaged DNA have been
identified, the most commonly measured being 8-oxodG (Halliwell and
Gutteridge, 2007; Wells et al., 2009b). Consequences of 8-oxodG
accumulation in dividing cells may lead to transversion mutations,
which can affect the expression and activity of proteins required for
normal development and function, and if not repaired, may affect gene
