The Mitochondrial Free Radical Theory of Aging - Supernova: Pliki

An Introduction to Free Radicals
Table 3.3. Reactions involving or protecting against LECs, cont.
22 b TocOH + L• TocO• + LH
23 b TocOH + LOO• TocO• + LOOH
24 b AscH2 + TocO• Asc• — + TocOH + H +
25 c Asc• — + Asc• — + 2H + AscH2 + Asc
26 g Asc + NADH + H +
AscH2 + NAD +
less of them than of the reagents that are used up. Most enzymes use metal atoms to achieve
their catalytic function: superoxide dismutase, for example, contains atoms of either manganese,
copper or zinc (different ones depending on the enzyme’s location).
3.6. Fenton Chemistry
Reactions 8 and 19 in Table 3.3 are distinguished by having a name: Fenton reactions.
They are particularly important for two reasons: one chemical, one conceptual. The chemical
reason is that they are the reactions which generate two major players in MiFRA: the hydroxyl
radical, HO•, which is far and away the most reactive substance that will concern us in this
book, and the alkoxyl radical, which is also highly toxic due to its involvement in branching
of chain reactions (see Section 3.7). The conceptual reason is that they are the main reactions
that switch the reactivity of their LEC participants from reductive to oxidative: the reactive
precursor, ferrous iron, is an eager electron donor, whereas the reactive product, hydroxyl or
alkoxyl, is an eager electron acceptor. Fenton reactions have attracted more attention from
gerontologists over the years than they may biologically merit: it is very unclear that the
levels of hydrogen peroxide or lipid peroxides anywhere in the body are sufficient to make
Fenton reactions a practical problem. If they did not need to alternate with other reactions
(see Section 3.5), they would be much more problematic: the attention they have attracted
in gerontology is possibly because some observers have overlooked this feature of the
chemistry. The only other reaction in Table 3.3 which is a switch from reductive to oxidative
reactivity is reaction 2, the protonation (condensation with a proton) of superoxide to form
perhydroxyl radical; this reaction, by contrast, may matter in vivo far more than has
traditionally been supposed. We will return to the role of perhydroxyl radical in detail in
Section 11.2.
3.7. Chains and Branches
Several of the reactions listed in the previous section fit together in patterns that are
much more elaborate than pairs, and it is their role in these patterns which underlies their
relevance to MiFRA.
A cumulative reaction that is capable of causing very rapid damage to membranes is the
lipid peroxidation chain reaction. It is composed of two of the reactions listed in Table 3.3,
which can alternate indefinitely in the presence of a supply of oxygen:
La• + O2
LaOO•
LaOO• + LbH LaOOH + Lb•
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