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Bioprotonics
Lev Verkhovsky (Moscow)
(January 2022)
From the author. The hypothesis of
R.Mikelsaar about the honeycomb-like
structure of the lipid biomembranes was
published in a scientific journal (1987)
00268948708070955.pdf
Then he published an article in the
Soviet popular science magazine "Chemistry
and Life" (1990, No. 4), and after that I
wrote a short paper "Bioprotonics", in
which I tried to develop the Mikelsaar
hypothesis in relation to bioenergetics. It
was published in the same magazine (1990,
No. 10).
Now I am presenting a translation of
my paper into English (with minimal
changes).
As the membranologists themselves admit, they have accumulated so much
experimental data that it has become difficult to navigate; some new generalizing
ideas are required. An interesting attempt was the hypothesis published in «Химия
и жизнь» (Chemistry and Life, 1990, No. 4) by a researcher from Tartu R.-H. N.
Mikelsaar about the honeycomb-like structure of the membrane.
An unexpected and even at first glance paradoxical feature of it is that the so-
called hydrophobic layer of the membrane (where lipid tails are enclosed) can, it
turns out, to a large extent consist of water. However, not ordinary -- liquid, but
structured, ice-like. The tubes of interconnected H2O molecules inside
phospholipid prisms were called "shafts". Since lipid matrices already limit the
mobility of water in the shafts, as if they freeze it, the change in the aggregate state
of the "water — ice" type in them and the associated phase transition of the entire
lipid film will be observed not at zero Celsius, but at a higher, possibly
physiological temperature (it primarily depends on the specific composition of
lipids).
The phase transition of the membrane, in turn, will affect the membrane
enzymes -- new cascades of reactions will turn on, which will change the
properties of the cell as a whole. As a result, the very weak initial signal that
caused the phase rearrangement will be amplified many times. In other words, such
a membrane will serve as a very sensitive biosensor -- chemical, when the
transition is induced even by single molecules, say, hormone or prostaglandin (this
was discussed in the Mikelsaar`s article), or physical, for example, with thermal
radiation.
In general, the aggregate state of the water in the shafts will be influenced by
a variety of factors, including, of course, the membrane potential. This
circumstance, apparently, is able to shed light on one of the key mysteries of
bioenergetics: how the universal cellular fuel is formed — the famous ATP. The
chemiosmotic theory proposed by Peter Mitchell (Nobel Prize for 1978) states that
during the oxidation of fats and carbohydrates by enzymes of the respiratory chain,
electric charges are transferred through the membrane, and then the created
electrochemical gradient of protons is used by another enzyme -- ATP synthetase,
which attaches inorganic phosphate to ADP:
ADP +Fn <---> ATP+H2O.
It has already been firmly established, that the membrane potential is the link
between oxidation and phosphorylation. But at the same time, it is still unclear
how this potential leads to the synthesis of ATP. Some researchers believe that first
it causes a conformational change in the enzyme, and then the internal energy of
the protein is used to form a chemical bond. However, this idea seems too general
and explains little.
Let's take another look at the above reaction of synthesis-hydrolysis of ATP.
It is clear that its equilibrium can be shifted to the right if one of its final products
(water) is diverted. Moreover, it is not necessary to physically transfer it
somewhere, but it is enough only to lower its chemical activity. Well, for example,
by transferring to ice, that is, freezing. And this function could be performed by the
membrane potential. We can suppose that the change in the aggregate state of
water in the membrane is the desired link between the membrane potential and the
synthesis-hydrolysis of ATP.
In fact, let the respiratory circuit work, the membrane is charged. As a result,
structural changes and phase changes are taking place in it. When the membrane is
charged, the water in it will become liquid (this is reported by the fluorescent
probes built into the membrane). But if now in some place several protons pass
through it down the gradient of their concentration, then locally, for a moment, the
membrane will discharge and the water in the shafts will freeze. This means that
the equilibrium will shift to the right -- to the synthesis of ATP. And in the
opposite direction: the membrane is not charged, the water in it is in a crystalline
state. But if we throw a few protons across the membrane (outward), then the ice
will melt locally and our reaction will go to the left (hydrolysis) -- in this case, the
enzyme operates in the ion pump mode.
In addition to this protein, there are other ion pumps in different membranes
(sodium-potassium, calcium) that transport ions through the membrane or,
conversely, synthesize ATP when the membrane capacitor is discharged. It is
natural to assume that they operate on the same principle, which, probably, could
be called "aquachemiosmotic".
It is important that protons can migrate through ice-like water by the "relay"
mechanism (known also as the de Grotthuss proton
“hopping” mechanism) -- this conduction has nothing to do with ion
diffusion.
The presence of ice shafts in the membrane allows us to return to a new level
to the analogy that was pointed out in 1958 by the future Nobel laureate Manfred
Eigen and Leo de Meyer from Germany. They drew attention to the fact that the
"relay" mechanism of proton conduction resembles the movement of electrons and
"holes" in conventional semiconductors. An electronic, n-type semiconductor
corresponds to ice with an excess of protons, and p-type -- with an excess of
hydroxyls, which are also like "holes" in water molecules that have lost one
hydrogen atom.
If you connect two pieces of ice with different types of carriers, then a shut—
off potential arises at the boundary separating them -- an analog, an n-p junction in
semiconductors, that is, a proton rectifier, a diode, will turn out. Eigen and de
Meyer noticed that since there are ice-like structures in the "pores of protein
membranes", this would be important for biology, where combinations of such
elements could give systems similar to those studied by technical cybernetics.
In a honeycomb-like membrane, the shafts are able to pass protons in one
direction -- in accordance with their orientation, and for other ions, the lipid
membrane can be considered an impenetrable barrier. On the other hand,
individual compartments of a cell can vary greatly in the concentration of
hydrogen ions (in their pH). An acidic environment is possible in one
compartment, an alkaline one in the other. According to the gradient of their
concentration, excess carriers will begin to seep into neighboring compartments,
and a shut-off potential will appear on the membrane separating them.
It is clear that such a membrane will be very susceptible to electric fields: in a
certain way, the applied field will enrich the close to membrane zone with current
carriers, current will flow through the boundary, the potential will be removed.
And this will cause a phase transition in it with all the consequences that follow
from this. A very important, but still poorly understood role of electric fields in the
body is being clarified.
But there is a complex, branched network of membranes in the cell — the
endoplasmic reticulum. This means that complexes of three compartments
separated by two membranes are possible there -- an analog of n-p-n-- or p-n-p--
junctions in semiconductors that form a triode -- the main element of electronic
circuits. And if so, what prevents a radio receiver or a computing device from
being assembled in a cell from such proton transistors?
Another Nobel laureate, Albert St. Gyorgy, wrote a small book called
"Bioelectronics" (1968). If the hypothesis about the honeycomb-like structure of
biomembranes is confirmed, then, apparently, it will be possible to start writing
"Bioprotonics"