The Mitochondrial Free Radical Theory of Aging - Supernova: Pliki

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The Mitochondrial Free Radical Theory of Aging
The LECs that are discussed throughout the rest of this book, and especially in the rest
of this chapter, are listed in Table 3.2. Also listed are the molecules which, though not LECs,
are important in MiFRA because they react with LECs and/or are formed by reactions
involving LECs.
3.5. LEC-Related Reactions Relevant to MiFRA
The reactions that will concern us in the rest of this book are described in Table 3.3;
several of the most important destructive ones are also depicted in Figure 3.1. The reactions
fall into the following categories:
a. donation of an electron by a LEC to a non-LEC — reduction
b. removal of an electron by a LEC from a non-LEC — oxidation
c. donation of an electron by a LEC to another LEC — usually disproportionation
d. fusion of a non-LEC with a LEC forming a LEC — condensation
e. fusion of a LEC with another LEC forming a non-LEC — termination
f. fission of a LEC forming a LEC and a non-LEC — dissociation
g. reactions not involving LECs but of relevance nevertheless
Because some of the reactions involve joining or splitting of lipids to form other lipids,
the equations that involve more than one lipid use subscripts a, b etc. to distinguish them.
Tables 3.2 and 3.3 may seem rather intimidating, but there is no need to absorb them;
they are supplied here mainly for ease of reference through the rest of the book. At this
point, the most important thing to appreciate about these reactions is the reason why I
defined “LEC” as I did: as noted in Table 3.1, reactions that happen in biological systems
preserve “LEC parity.” That is, if you start with an odd number of LECs you end with an odd
number, and if you start with an even number of LECs you end with an even number. This
is not so for free radicals, nor for reactive oxygen species.
It is also worth stressing at this point that not all LECs behave in the same way. For
example, the reaction between two ascorbate radicals and that between two lipid radicals
are completely different: the former involves the incorporation of two protons, whereas the
latter uses no protons but instead makes a bond. This is a crucial difference, because the
bond is permanent, whereas the oxidised ascorbate (dehydroascorbate) is still an independent
molecule which can be restored to its reduced form. This property of ascorbate, together
with its extreme readiness to undergo disproportionation, is the main reason why it is so
valuable to us.
A third crucial feature which should be observed in this list is that some pairs of reactions
cause the change of one participant to a different form and then back again. For example,
superoxide turns ferric iron into ferrous, and hydrogen peroxide turns it back to ferric.
Putting those two reactions in sequence:
O2• — + Fe 3+
H2O2 + Fe 2+ • +H +
O2• — + H2O2 +H +
O2 + Fe 2+ •
HO• + H2O + Fe 3+
HO• + H2O + O2
gives us a chemical change which, if thought of as a single reaction, doesn’t involve iron at
all.
But that cumulative reaction does not appear in Table 3.3, and the reason it doesn’t
appear is that it doesn’t happen. Iron (or copper, or some other ion that behaves the same
way) needs to be present so that the intermediate state is available. Iron therefore acts as a
catalyst, causing a normally impossible reaction to be achieved by a detour that needs less
activation energy. This is the way that all catalysts work, and why a reaction needs so much