Biophysical Electrochemistry and Human Metabolism

Oxidation is a word that gets tossed around a LOT in discussions of nutrition and metabolism.  And for good reason -- it is integral to how our bodies "burn" fuels for energy and how that energy is harnessed to drive all manner of chemical reactions.    I spent my graduate years studying oxidation -- in metals -- but in many ways the principles are the same.  A little while ago I came across the following paper:  The Pecking Order of Free Radicals and AntiOxidants: Lipid Peroxidation, α-Tocopherol and Ascorbate.  In it we find the following chart:

What the heck is that?  Well, it bears a striking resemblance to one of these tables at right -- A Standard EMF Series (EMF = electromotive force) for metals.  Another word commonly referencing this EMF is "potential".  The relative potential  indicates the tendency of each of the metals shown on the abbreviated series to lose or gain electrons -- that is, to be oxidized or reduced respectively.  On the far right we have a nickel-cadmium electrochemical cell ... aka a battery.  Since Ni has a higher potential than Cd, it is "less active" or prone to oxidation than Cd.  If we set up the cell as shown, with a standard concentration of a corresponding metal ion in solution in each compartment, we can measure a voltage of this cell.  If we then connect the metals with a wire (providing a conductive path for the electrons), the voltage/potential differential drives the flow of electrons -- aka an electrical current.  Any battery operated device harnesses that electrical energy to do mechanical work, generate heat, light, etc.

The oxidation of metals is generally called corrosion and usually considered a detrimental process that can alter the appearance, mechanical integrity and properties such as conductivity, ductility, surface friction, etc. of metals.  However, harness that oxidation as in the battery, and it's actually a "good thing".  We are all well familiar with rusting of iron, but before all of our outdoor trash cans were made of plastic, they were made of galvanized steel.  Galvanized steel is iron, Fe, coated with zinc, Zn.  Since Fe is above Zn on the series, the Zn oxidizes and in doing so, protects the Fe from being oxidized, or rusting, as it would normally be subjected to due to hydrogen and oxygen in the environment.  Zinc is like an antioxidant for our trash can!  We would call Fe-Zn a "redox couple" in this scenario.

So it struck me quite a while ago that a lot of the biochemistry we look at in metabolism is more like electrochemistry than organic chemistry, or "o chem" per se.  O chem focuses more on structure and the mechanisms by which reactions occur, classifications of molecules, etc.  This branch of chemistry is more involved in understanding how various enzymes, hormones, receptors and transporters operate to facilitate our biochemistry.  But the reactions themselves and what drives them in our bodies are not a whole lot different than the metallurgical electrochemistry, we're basically talking biological and physical  electrochemistry -- what I'll call biophysical electrochem for short.

I'm going to first lay some groundwork of basic chemistry -- structure of matter, bonding, etc., chemical reactions including reversible reactions and chemical equilibrium.  Then we can discuss oxidation reactions and biological redox couples -- how our bodies harness chemical potential energy and make use of coupling oxidation and reduction reactions -- just as in the battery -- to sustain many of the processes we know as life.  Because one main actor in these reactions is the H+ ion, we'll discuss a bit about acids and bases as well.  While I'll probably bore half my audience to death breaking this down, I hope to help some of you navigate the sea of utter bullshit -- there's no delicate term for some of it -- out there vis a vis mitochondrial function, ROS (reactive oxygen species) and the electron transport chain.  In discussing the ETC protein complexes, ATP production and uncoupling proteins we will necessarily have to expand this discussion past strict redox chemistry to chemio-osmotic phenomenon that harness ionic currents (bioelectricity) to drive reactions.

The assertion that somehow fatty acid oxidation for energy is preferable to glycolysis is one of the latest gimmicks out there as folks following these generally opportunistic gurus increase their fat consumption and reduce protein consumption in search of some "Holy Grail" of metabolism ... or nutritional ketotic nirvana ... to be a fat burning beast ... burn low and slow or fast and furious depending on which guru you follow.   Is it true?  I'd say the jury is out and there's at least as much evidence out there to support a glucose dominated metabolism, or better yet, IMO, the notion of agnostic mitochondria so long as they are well nourished but not over nourished.

Hopefully in the end, we can sort through some of what is true and that which is woo in this whole realm of mitochondrial dysfunction, insulin resistance, diabetes and all manner of "metabolic derangement".  In the context of the electrochemistry involved we can sort through what impact, if any,  the macronutrient composition of one's diet and/or its caloric content may have, and other  factors like genetics that are at play.  To the latter there is ever emerging peer review literature to discuss, but as to the relationship between diet and mitochondrial function, the waters are far more murky.   I invite everyone, including detractors, to participate here in the comments as only by discussing these things and being challenged can we endeavor to arrive at the truth to the best that the available scientific evidence allows us.