Pyrroloquinoline Quinone and Mitochondria

Mitochondria are the power generators of cells. They generate energy through our aerobic processes. They do this by breaking down glucose metabolites, fatty acids, and certain amino acids aerobically or in the presence of oxygen, to release energy. Aerobic energy release is a critical driver of athletic performance, especially in endurance sports. Mitochondrial energy production supports activities such as running and other endurance activity. When it comes to short duration bursts of activity, as seen with sprints that need fast twitch muscle fibers, additional anaerobic processes are employed by the body.

Pyrroloquinoline quinone (PQQ) is coenzyme that is purported to help with mitochondria function, for instance, mitochondrial biogenesis. Recent studies suggest PQQ does this by activating genes that oversee mitochondrial protection, reproduction, and repair.

Metabolic Process

Before with go deep into PQQ and mitochondria, let’s first quickly look at the metabolic process of glycolysis. Glycolysis is the process whereby glucose is utilized within human cells to generate energy for the functioning of the body. It is a sequence of ten reactions that produce ten intermediate compounds. This process with variations has been observed in most organisms and is considered a universal pathway for energy production. There were several scientists who contributed at different points of time toward the elucidation of the reactions in glycolysis. They include Louis Pasteur (1860), Eduard Buchner (1890), Arthur Harden & William Young (1905), Otto Meyerhof and Luis Leloir (1940s).

Glycolysis takes place in the cytoplasm of the cell. It is the first step in both the aerobic and anaerobic respiratory pathways. Glycolysis does not require oxygen. During glycolysis, a molecule of glucose is split into 2 molecules of pyruvate, utilizing 2 molecules of adenosine triphosphate (ATP). At the end of the process, 4 molecules of ATP are released, resulting in a net gain of 2 ATP. Further, this process generates 2 molecules of NADH which are also converted in the next stage of the respiratory process into ATP. ATP is utilized by the body as fuel to generate energy. Pyruvate is then transported to the mitochondria which are organelles within the cytoplasm of the cell for further breakdown and energy release.

There are 3 regulated enzymes that play a role in glycolysis. These are hexokinase, phosphofructokinase and pyruvate kinase. The steps in the glycolysis pathway that utilize these enzymes are irreversible. Energy production through glycolysis is regulated by varying the concentrations of these enzymes in the cytoplasm based on the body’s energy needs. Genetic mutations that affect glycolysis are usually not compatible with life.

Mitochondria and ATP

Mitochondria are infinitesimally small and roughly the size of bacteria. They are seen in the cytoplasm of cells. They have a double-layered wall and the inner layer has multiple folds that are called cristae. These folds increase the surface area of the inner layer which is where energy production takes place. Energy is produced in the form of ATP. ATP is adenosine triphosphate and this is a molecule that functions like a rechargeable battery. The energy released from any metabolic process gets stored in this molecule and when the body requires energy, ATP is broken down to release energy.

As a quinone, PQQ possesses the chemical attributes to be a good agent in electron transfer reactions. It is also a cell-signaling molecule that seems to optimize mitochondrial production, even if there is limited evidence to suggest its direct involvement with ATP.

There is a hypothesis that these organelle (mitochondria) were originally bacteria themselves that found a place to live inside eukaryotic cells. This idea is strengthened by the fact that there is genetic material (DNA) inside the mitochondria that are independent of the DNA in the chromosomes of the cell nucleus. Mitochondria and the DNA within it are inherited from the mother which means endurance capacity is inherited maternally!

Mitochondrial enzyme production is triggered by endurance exercise. Mitochondrial density goes up with training. Optimal density of mitochondria in skeletal muscles is required for athletes to perform at their peak potential. Mitochondrial density increases in response to two stimuli in general 1) When calcium ion levels inside skeletal muscle cells go up – this happens during each muscle contraction and 2) When there is a deficiency of ATP molecules in the muscle cells – which happens when more ATP is being used up than are being synthesized as happens during intense exercise.

Research on endurance exercise and its impact on mitochondrial enzymes has shown that enzyme concentrations do not increase significantly with sustained exercise beyond 60 minutes. High-intensity exercises that are close to or over the athletes VO2 Max performed in interval training mode for a cumulative period not exceeding 30 minutes a day can increase mitochondrial enzyme concentration to similar levels as lower intensity exercises performed over longer durations.

In order to develop mitochondrial density, it thus benefits to engage in endurance exercise at or above the athlete’s VO2 Max for short periods/ intervals during each training session. These short periods at or above VO2 Max should be prolonged as long as possible for any given intensity. In a trained athlete, one who is maintaining an optimal diet, additional PQQ supplementation is likely not beneficial.

Control of mitochondrial oxygen utilization and respiratory control is central to all aspects of normal growth and development.  In a broad setting, mitochondria are central to normal glucose, amino acid & fatty acid oxidation, reactive oxygen species (ROS), i.e., antioxidant modulation, and ATP production, particularly during exercise.  The mechanisms for mitochondrial regulation involve changes in the number of mitochondria per cell, the assembly & disassembly of mitochondria, control of transport of substances into and out of mitochondria, as well as control on the levels of activity of mitochondrial-related enzymes. Indeed, the importance of mitochondria to energy regulation cannot be understated. Mitochondria generate most of the cell’s supply of ATP, which is the major source of a cell’s potential chemical energy.

Mitochondria and PQQ Usage

Moreover, in addition to supplying cellular energy, mitochondria are also important to cellular regulatory signaling, and the eventual programmed cell death (or apoptosis) and turnover of cells. The lifespan of all cells is directly linked to mitochondrial assembly and production. Such events can control new tissue growth, the response to infections, and nerve cell signaling and control.  In the average adult, between 50 and 70 billion cells turnover each day due to apoptosis per programmed cell death.  In a year, this can amount to the proliferation and subsequent destruction of a mass of cells equal to one’s body weight!  When mitochondrial function at any level is compromised there can be a number of metabolic and health-related metabolic consequences.  Examples are a decline in mitochondrial oxidative efficiency, which is thought to be a major underlying feature of the metabolic syndromes that can lead to increased blood pressure and lipid levels, poorer responses to inflammation and, when targeted and severe, neurological disorders, such as Parkinson’s disease and Alzheimer’s dementia. In these cases, further research is needed to see if PQQ supplementation would be beneficial. To learn more about the general benefits of taking a PQQ supplement, see an overview of the benefits of increasing pyrroloquinoline quinone intake here.