The charging of the battery, in which ADP and a free phos phate group are combined to res tore
ATP, is coupled to the oxidative proces s ; the clos e linking is known as coupled phos phorylation.
If the combination becomes uncoupled, the means is los t for providing us able energy.
Res piration continues but no energy is produced. The cell has become like a racing engine,
generating heat but yielding no power. The n the mus cle cannot contract, nor can the i mpuls e
race along the nerve pathways. Then the s perm cannot move to its des tination; the fertilized
egg cannot carry to completion its complex divis ions and elaborations. The cons equences of
uncoupling could indeed be dis as trous for any organis m from embry o to adult: in time it could
lead to the death of the tis s ue or even of the organis m. How can uncoupling be brought about?
Radiation is an uncoupler, and the death of cells expos ed to radiation is thought by s ome to be
brought about in this way. Unfortunately, a good many che micals also have the power to
separate oxidation from energy producti on, and the ins ecticides and weed killers are well
repres ented on the lis t. The phenols , as we have seen, have a strong effect on metabolism,
causing a potentially fatal rise in temperature; this is brought about by the ‘racing engine’ effect
of uncoupling. The dinitrophenols and pentachlorophe nols are examples of this group that have
wides pread us e as herbicides. Anothe r uncoupler among the herbicides is 2,4-D. O f the
chlorinated hydrocarbons, DDT is a proven uncoupler and further s tudy will probably reveal
othe rs among this group. But unc oupling is not the only way to extinguis h the little fires in
some or all of the body’s billions of cells. We have s een that each s tep in oxidation is directed
and expedite d by a s pecific enzyme. Whe n any of thes e enzy mes—eve n a s ingle one of the m—
is destroyed or weakened, the cycle of oxidation within the cell comes to a halt. It makes no
difference which enzy me is affected. Oxidation progres s es in a cycle like a turning wheel. If we
thrus t a crowbar betwee n the spokes of a wheel it makes no difference where we do it, the
wheel s tops turning. In the s ame way, if we des troy an e nzy me that functions at any point in
the cycle, oxidation ceas es. There is then no furthe r energy production, s o the end effect is very
similar to uncoupling.
The crowbar to wreck the wheels of oxidation can be s upplied by any of a numbe r of c hemicals
commonly us ed as pes ticides. DDT, methoxychlor, malathion, phenothiazine, and various
dinitro compounds are among the nume rous pes ticides that have been found to inhibit one or
more of the enzy mes concerned in the cycle of oxidation. They thus appear as agents
pote ntially capable of blocking the whole proces s of energy production and depriving the cells
of utilizable oxygen. This is an injury with mos t dis as trous cons equences , only a few of which
can be mentioned here. Merely by systematically withholding oxygen, experimenters have
caused normal cells to turn into cancer cells, as we shall see in the following chapter. Some hint
of othe r dras tic cons equences of depriving a cell of oxygen can be s een in animal experiments
on devel oping embry os. With ins ufficient oxygen the orderly proces s es by which the tis s ues
unfold and the organs develop are dis rupte d; malformations and othe r abnormalities then
occur. P res umably the human embryo deprive d of ox ygen may als o develop c ongenital
deformities.
There are s igns that an increas e in s uch dis as ters is being noticed, even though few look far
enough to find all of the caus es. In one of the more unpleas ant portents of the times , the Office
of Vital Statistics in 1961 initiated a national tabulation of malformations at birth, with the
explanatory comme nt that the res ulting s tatis tics would provide neede d facts on the incidence
of congenital malformations and the circums tances under which they occur. Such s tudies will
backadmin
(backadmin)
#1