78
N. R. Jena et al.
This theoretical study [174] revealed that the SET mechanism would operate only
in polar media while the HAT mechanism would operate in all the solvents though
it would also be more favoured in polar media. The most favoured site of β-carotene
for hydrogen abstraction was found to be C4 of the β-ionone ring (Fig. 3.7a).
Structural changes occurred in β-carotene due to addition of NO 2
•
at any of the
carbon atoms of the polyene chain [174]. It resulted in breaking of the conjugated
system and partial loss of planarity of the chain. Addition of NO 2
•
at any of the C5
and C6 positions of the β-ionone ring caused ring twisting which had a noticeable
effect since the double bond of the ring remained only partially conjugated with the
polyene chain. The adduct BC(C5)-NO 2
•
was found to be the most stable among all
radical adducts confirming this site to be the most favoured one for the RAF mechanism [174]. A greater stability of the BC(C5)-NO 2
•
adduct than that of BC(C6)NO 2
•
was due to a combination of two effects i.e. stabilization by resonance of
the unpaired electron which does not occur in the latter, and partial extension of
planarity of the conjugated polyene chain to the end groups by proper twisting of
the β-ionone rings.
3.4.5 ONOO
−
Scavengers
Xanthine and hypoxanthine are formed from guanine following its oxidation. Uric
acid (UA) is formed as a reaction product of xanthine and hypoxantine during the
metabolic activities. UA has been shown to have ONOO
−
scavenging ability that
significantly reduces nitration of tyrosine. Thus UA prevents inflammatory cell invasion into the central nervous system [179, 180]. Similarly, marine extracts like
2,3,6-tribromo-4,5-dihydroxybenzyl methyl ether can also act as potential ONOO
−
scavengers [181]. It has been shown that compounds that contain galloyl group
exhibit high ONOO
−
scavenging activity. For example, several components of the
green tea tannin such as epigallocatechin 3-o-gallate (Fig. 3.7m) and gallocatechin
3-o-gallate have been shown to scavenge ONOO
−
actively [182].
The above discussion shows that there is a strong support in favour of ability of
the anti-oxidant molecules to scavenge ROS and RNOS which cause DNA damage
and produce mutagenic products. Application of density functional theory has been
particularly very useful in this context.
3.5 Enzymatic DNA Repair
Enzymatic DNA repair mainly depends on three vital processes, i.e. (1) protein
translocation, (2) identification of the target, and (3) lesion repair by catalysis.
These processes are discussed below.
N. R. Jena et al.
This theoretical study [174] revealed that the SET mechanism would operate only
in polar media while the HAT mechanism would operate in all the solvents though
it would also be more favoured in polar media. The most favoured site of β-carotene
for hydrogen abstraction was found to be C4 of the β-ionone ring (Fig. 3.7a).
Structural changes occurred in β-carotene due to addition of NO 2
•
at any of the
carbon atoms of the polyene chain [174]. It resulted in breaking of the conjugated
system and partial loss of planarity of the chain. Addition of NO 2
•
at any of the C5
and C6 positions of the β-ionone ring caused ring twisting which had a noticeable
effect since the double bond of the ring remained only partially conjugated with the
polyene chain. The adduct BC(C5)-NO 2
•
was found to be the most stable among all
radical adducts confirming this site to be the most favoured one for the RAF mechanism [174]. A greater stability of the BC(C5)-NO 2
•
adduct than that of BC(C6)NO 2
•
was due to a combination of two effects i.e. stabilization by resonance of
the unpaired electron which does not occur in the latter, and partial extension of
planarity of the conjugated polyene chain to the end groups by proper twisting of
the β-ionone rings.
3.4.5 ONOO
−
Scavengers
Xanthine and hypoxanthine are formed from guanine following its oxidation. Uric
acid (UA) is formed as a reaction product of xanthine and hypoxantine during the
metabolic activities. UA has been shown to have ONOO
−
scavenging ability that
significantly reduces nitration of tyrosine. Thus UA prevents inflammatory cell invasion into the central nervous system [179, 180]. Similarly, marine extracts like
2,3,6-tribromo-4,5-dihydroxybenzyl methyl ether can also act as potential ONOO
−
scavengers [181]. It has been shown that compounds that contain galloyl group
exhibit high ONOO
−
scavenging activity. For example, several components of the
green tea tannin such as epigallocatechin 3-o-gallate (Fig. 3.7m) and gallocatechin
3-o-gallate have been shown to scavenge ONOO
−
actively [182].
The above discussion shows that there is a strong support in favour of ability of
the anti-oxidant molecules to scavenge ROS and RNOS which cause DNA damage
and produce mutagenic products. Application of density functional theory has been
particularly very useful in this context.
3.5 Enzymatic DNA Repair
Enzymatic DNA repair mainly depends on three vital processes, i.e. (1) protein
translocation, (2) identification of the target, and (3) lesion repair by catalysis.
These processes are discussed below.