~~~  lecture notes by Thomas L. Hesselink, MD  ~~~
              5th Edition,  Copyright 2002 


This lecture reviews the metabolism of reducing equivalents 
(electrons and hydrogen atoms). 

All living things depend upon the orderly transfer of reducing 
equivalents from food/fuel molecules to some final electron 
acceptor. In "aerobic" organisms diatomic oxygen is most 
frequently utilized as the final electron acceptor. However, 
under special circumstances, hydrogen peroxide or pyruvate 
can also be used. In "anaerobic" organisms weaker oxidants 
such as sulfate, carbon dioxide, nitrate, or pyruvate are 
used as final electron acceptors.

In living things some transfers of electrons and hydrogen 
atoms take place as simple two reactant oxidation-reductions, 
such as occur in a test tube or battery. However, most 
transfers occur in multi-step sequences which are carefully 
regulated. Thus reducing equivalents pass from one carrier 
in the sequence to the next, much like buckets along a bucket 
brigade or batons in a relay race. Their movement is governed 
by: reactant concentrations, relative redox potentials, pH, 
and enzymatic facilitation. These delicate systems can be 
blocked by respiratory poisons such as: mercury II, ammonia, 
cyanide, or sulfide. They can also fail due to nutritional 
deficiency of key components such as: riboflavin, copper, 
selenium, ascorbate, bioflavonoid, or cysteine. 

Diseases such as allergies, infections, and cancers are 
associated with some focus of failure in a biological 
electron transfer sequence. This failure allows an excess 
of reductant materials of various types to accumulate and 
support the disease process. Therapeutic oxidants accelerate 
the removal of these reductants. When successful, the 
therapeutic oxidant administered consumes enough reductant 
material such that the pathologic process cannot persist. 

Medicinal oxidants need not abstract electrons or hydrogen 
atoms directly from the site of pathology. Instead the 
process can be quite indirect. In other words the medicinal 
oxidant can abstract reducing equivalents from any of several 
ambient hydrogen/electron carriers. As these oxidized carriers 
get physiologically recharged, electrons or hydrogen atoms 
are drawn away from other sites. This includes the pathologic 
site. A considerable variety of oxidants can induce this 
redistribution of reducing equivalents. This explains why 
so many different oxidizing agents have been found to produce 
similar therapeutic benefits. 

Also medicinal oxidants can produce numerous physiologic 
effects. These include: enhanced release of oxygen from 
oxyhemoglobin, stimulated release of immunoactive cytokines, 
antioxidant adaptation, and initiation of programmed cell 
death in certain cells. 

This lecture introduces the most common types of electron 
carriers and hydrogen carriers found in living things. 
It explains the molecular mechanisms whereby each can be 
oxidized and reduced reversibly. Several types of biological 
electron transfer sequences (BETS) are illustrated, and 
their are functions identified. How medicinal oxidants alter 
the flow and distribution of reductants along the myriad 
BETS is explained. As these alterations take place the 
benefits of the medicinal oxidant begin to manifest. 
Thus the biochemical mechanisms underlying the oxidative 
therapies will become apparent.