The Mitochondrial Free Radical Theory of Aging - Supernova: Pliki

10
The Mitochondrial Free Radical Theory of Aging
In addition to these “carrier” proteins, several enzymes are embedded in the inner
membrane. In a sense these enzymes are the clients of the carrier proteins; their roles
(discussed in Sections 2.3.3 and 2.3.4) are central to mitochondrial function, but the
substrates whose reactions they catalyse must be made available on the correct side of the
inner membrane.
Most of the transmembrane enzymes and carriers are actually complexes, made up of
more than one protein—in one case, more than 40. 11 Each is present in a few thousand
copies per mitochondrion.
2.3. Mitochondrial Function
Mitochondria enable us to use oxygen.
Virtually everything that our cells need to do to keep themselves—and hence us—alive
requires energy. We use energy in macroscopic ways, of course, in movement and in keeping
warm; but the microscopic processes that our cells are doing all the time, such as construction
of proteins, replication of DNA and so on, also need energy. This energy comes from nutrients
in what we eat; the chemical bonds in those nutrients (such as sugars and fats) are changed
into other types of bond (such as in carbon dioxide and water) which have less energy. The
difference between these energies is thus available to cells. Oxygen, and hence mitochondria,
are intimately involved in these processes.
2.3.1.Three Ubiquitous Reservoirs
2.3.1.1. A Terminological Apology; The Proton Reservoir
Almost all the chemical reactions that will be discussed hereafter occur in water. (The
rest occur within membranes.) Many of them involve acids. The characteristic that makes a
molecule acidic is that, when it is dissolved in water, it tends to break apart in a particular
way: one hydrogen ion (which is simply a proton) comes off. It turns out that water itself
does this to a small extent—protons become detached, leaving hydroxide anions.* Conversely,
the characteristic that makes a molecule alkaline is that it comes apart in water in a different
way, whereby one hydroxide anion comes off.** Water, therefore, effectively does both when
it comes apart. The coming-apart is very transitory: protons constantly jump between water
molecules, so that individual hydroxide anions reacquire a proton almost instantly after
they come into existence. The proportion of water molecules that are dissociated at any one
time is about 10 -7 in pure water at room temperature and pressure, which is why “neutral
pH” is defined as pH 7. We will come back to these aspects of water in Section 11.3.1.
The tendency of water reversibly to come apart like this has a profound chemical
consequence in biological systems: it means that protons are available for incorporation
into a chemical reaction whenever needed, and similarly they can be discarded at will. In
effect, the water that comprises 70% of our mass is a huge reservoir of protons.
Now for the terminology problem. When an acid reacts with an alkali, it forms a
compound whose chemical name is constructed from those of the reagents—sodium
chloride, for instance, or sodium acetate. But while such molecules are in solution, their
* The detached protons do not, in fact, remain free in solution, but form bonds to intact water molecules
making molecules of H3O + , which is called hydronium. We will come back to this in a discussion of water’s
conductivity, in Section 11.3.1, but meanwhile it need not concern us—the protons can be considered to be
free in solution.
** Or, in some cases, whereby nothing comes off but instead a proton is removed from a nearby water molecule
leaving the water as hydroxide.