Two facts about heart disease have long been known. First, it is the leading cause of death in industrialized countries. Second, smoking and high cholesterol are often precursors for heart attacks. Scientists have puzzled, however, over the fact that over half of heart attacks strike non-smokers with moderate cholesterol levels. New research suggests that the explanation may lie within the mitochondria, the power plants inside our cells. It appears that an "unbundling" mechanism creates a short circuit that diverts energy production and causes free radical damage that contributes to atherosclerosis. For details on this research, click here. "Vascular respiratory uncoupling increases blood pressure and atherosclerosis." Nature. 2005 May 26;435(7041):502-6. This Research Update column highlights articles related to recent scientific inquiry into the process of human aging. It is not intended to promote any specific ingredient, regimen, or use and should not be construed as evidence of the safety, effectiveness, or intended uses of the Juvenon product. The Juvenon label should be consulted for intended uses and appropriate directions for use of the product.

By Benjamin V. Treadwell, Ph.D.

To achieve a scientific breakthrough, it often takes an iconoclast who breaks ranks with the establishment. Peter Mitchell, a British chemist, fits the profile. In the early 1960’s, Mitchell single-handedly made a discovery that previously baffled the brightest scientists. Today, his discovery points the way towards improved health for aging cells.

The ATP Energy Mystery Solved

The mystery that he solved was how cells convert food to the chemical form of energy, ATP (adenosine triphosphate). This energy-producing process was generally known to occur in the subcellular structures, the mitochondria. Mitchell was the first to put forth a theory – seen as wild at the time - to explain how the body manufactures energy. His Nobel Prize-winning insight was that the mitochondria work like storage batteries.

Bear with me, now, as I explain Mitchell’s theory. Your reward will be a better understanding of how to age in good health. Mitchell’s theory explains the final pathway in the conversion of food to energy. At that time, it was known that food is first broken down to specific metabolites by the action of enzymes. Enzymes acting on these metabolites extract electrons and protons (negative and positive charges) from them. This was where the confusion in this field rested. It was surmised that electrons were somehow involved in energy production, but the mechanism was not known. Mitchell postulated that the protons were pumped to the exterior by some yet to be discovered mechanism. Later it was shown that Mitchell was correct.

Once extracted from food, the protons are immediately attached to a carrier protein that ferries them out of the inner chamber of the mitochondrion and across a semi-permeable membrane (inner mitochondrial membrane) where they are deposited on the external membrane surface. (The membrane is impermeable to the electrons, so they remain on the inside surface of the membrane.) In effect, the process, called separation of charge, creates a battery much like the battery in your car.

The outside positive charge is strongly attracted to the negative charge on the inside of the membrane. The protons and electrons accumulate on the outside and inside of the semi-permeable membrane. This charge separation creates what is known as the membrane potential. The greater the number of charges separated by the membrane, the greater the membrane potential.

How does this separation of charge convert to chemical energy that the body can use? This was a sticking point in Mitchell’s theory, since it was not clear how the energy trapped in the form of separated charge, the membrane potential, is converted into ATP. It turned out that the membrane separating the two opposing charges contains specific tunnels that allow for the passage of the positive proton to meet up with its negative mate, the electron. As it passes through this tunnel, the proton comes in contact with a structure that seemingly blocks the tunnel, but in fact, this structure is much like a revolving door.

Once the proton contacts the revolving door, it puts the door in motion, allowing the proton to pass through. The motion of the revolving door brings together two chemicals that were bound to separate sites on the enzyme. The two chemicals are ADP (adenosine diphosphate) and phosphate. As a consequence of the door motion, the two chemicals are now so close to one another that they interact to form a chemical bond, generating the high-energy compound, ATP. The proton’s reward for doing this work is it gets to combine with its mate the electron on the inside of the membrane.

OK, now that you’ve made it through the technical detail, you want to know what relevance it has to our health. The background was necessary to illustrate why this battery is so important to aging, disease and our over-all health.

It turns out that when one overeats or consumes too much junk food laden with sugar, the mitochondria produce lots of electrons and protons. Consequently, membrane potential dramatically increases. High food intake also stimulates the pancreas to produce more insulin and release it into the blood stream. This too speeds up the mitochondrial production of electrons and protons, and increases membrane potential. The result is an overcharged battery. Overcharged mitochondria become sloppy. Electrons escape from the machinery, combine with oxygen, and form free radicals – destructive agents that cause cellular damage. This is especially true of those who not only eat to excess, but also do little exercise to burn off excess ATP and lower the membrane potential.

This condition - high membrane potential and associated increase in free radical production - appears to be causally associated with the pre-diabetic state and with atherosclerosis. More recent evidence indicates the most appropriate way to avoid this condition is to maintain a lifestyle, via diet and exercise, that helps maintain a low insulin level while increasing the burning of fat from fat stores. It appears that the mobilization of fat from our stores increases free fatty acids (FFA’s) in our blood, to be utilized for energy production in our mitochondria.

These mobilized FFA’s can act to discharge high mitochondrial membrane potential by stimulating the tunnel-transport of the positive charge from the membrane exterior via a separate non-ATP-producing tunnel. This acts as a safety valve to purge the membrane potential by uncoupling the production of ATP via movement of the proton to the interior of the mitochondria. This lowering of the membrane potential attenuates the free radical production associated with the overcharged battery.

The healthy formula is: Energy production = energy consumption. The amount of ATP produced should equal the amount you use each day to carry out physical and mental activity. The unhealthy cell contains mitochondria bloated with ATP that create high membrane potential and spew out cell-damaging free radicals. In the natural state we use our stores of fat for energy production on demand. It is unnatural to use sugar-dense foods (junk foods) as a source of energy, because they bypass built-in cellular safety valves that protect us from free-radical damage.