Re: [HAPS-L] End-product inhibition

[Ken Saladin <ksaladin@xxxxxxxxxx>]

> On a recent essay
> exam I asked my students to give me an example of negative
> feedback.  Most used
> parameters such as glucose concentration, temperature, even calcium
> concentrtion.  Two students however
> used "end-product inhibition" of enzymes (with specific
> examples).  I''m just curious, do most of you
> consider this negative feedback in the classical sense?
>
> Thanks
> Chet Harbut, Ph.D.



I think this is an excellent example of negative feedback, and I
think it's fallacious to assume that negative feedback has to involve any
sort of integrating center or control system. Sometimes it does,
sometimes it doesn't. All that is necessary for negative feedback, in my
opinion, is that a chain of reactions or processes is set into action and
the end-product or final result of these processes has the effect of
reversing (negating) the original change that started the whole thing.

Another example of negative feedback without an integrating or control
system in the usual sense is seen in edema (or its prevention). The
buildup of pressure in the interstitial fluid forces the valves of the
lymphatic capillaries open, the lymphatics absorb more fluid, and this
brings down the interstitial fluid pressure -- thus reversing the change
that started the process. Thereby, the homeostatic regulation of
interstitial fluid volume is achieved.

In The Wisdom of the Body (p. 290), Walter Cannon referred to shifts in
tissue fluid as "storage by inundation" and remarked "It
appears to have no specially developed control other than the relative
concentration of the substances concerned...."  If we construe
negative feedback as a physiological process that maintains homeostasis
by reversing an initial change, then all sorts of processes can qualify
that have neither neural nor endocrine sensors or integrators.

Aside from end-product inhibition, another good case of negative feedback
where the only "sensor-integrator" is a molecule is the Bohr
effect in oxyhemoglobin dissociation.

> But,  if we
> consider "end-product inhibition" to be negative feedback then
> we must also consider chain reactions and cascades to be positive
> feedback 

No we don't, because positive feedback means the end-result or
end-product feeds back and accelerates the change that initiated the
process. That's not so in cascades. For example, an activated kinase does
not (to my knowledge) feed back and accelerate the activation of
adenylate cyclase in the cAMP second-messenger system. Fibrin does not
feed back and accelerate the activation of factor XII in blood clotting.
These cascades certainly have an amplification effect (enzyme
amplification), but they lack the self-accelerating feedback aspect.


Ken