Oxygen: Origins and Biology – Part 1

Oxygen: Origins and Biology - Part 1

Oxygen and Health Optimization

On the journey towards optimal health and longevity, oxygen is double-edged sword that can provide incredible health benefits through both its embellishment and constriction. Although the often-vague concept of oxygen finds itself in a paradigm of the more, the better’ there is significant nuance around this invisible molecule that we inhale thousands of times every day. As we breath in and out, a delicate dance of biology unfolds in the subconscious recesses of physiology and 02 is simultaneously indispensable for human life and consistently feeding into entropic unfolding. Learning how to consciously utilize this molecule of 02 can be a potent means of increasing and optimizing health in various ways.

In this article, the following components of the oxygen landscape will be reviewed:

Discovery of oxygen
What oxygen is: structure and genesis
Uses of oxygen
Biology of oxygen: respiration and the Krebs Cycle

Discovery of Oxygen

Over 500 years ago, Leonardo da Vinci suggested that the air we inhale may contain something vital to life after noticing that combustion seemed to remove this hypothetical and mysterious substance from air, causing animals to suffocate. Many medieval alchemists also tried to find it though without success.

Subsequently, a substance identified as oxygen may have occurred as early 1598 – 1604 by Polish alchemist, philosopher, and physician Michael Sendivogius and was noted in his work ‘Twelve Treatises on the Philosopher’s Stone drawn from the source of nature and manual experience’ which described a substance contained in air, referring to it as ‘cibus vitae’ (food of life) (1). In 1774, the English chemist Joseph Priestley succeeded in both separating out the substance, and showing it was a single chemical element, rather than a special mix of gases. This discovery was expanded upon by other and future scientists and the chemical structure of oxygen was elucidated.

(1) Marples, Frater James A. “Michael Sendivogius, Rosicrucian, and Father of Studies of Oxygen” Societas Rosicruciana in Civitatibus Foederatis, Nebraska College. pp. 3–4. Archived from the original on May 8, 2020. Retrieved May 25, 2018.

What is Oxygen?

Chemical Structure of Oxygen

When many of us think about oxygen, we imagine a ubiquitous molecule that is synonymous with life. We may think of breathing and drawing in these molecules of 02 into the lung so they can be distributed throughout the body and into the cells. But what exactly is oxygen?

Oxygen is a chemical element with the symbol O and atomic number 8 and is a member of the chalcogen group (also known as the oxygen group) in the periodic table. It is a highly reactive nonmetal/gas and a potent oxidizing compound that easily forms oxides with most other elements as well as with other compounds. Oxides are binary chemical compounds with one or more oxygen atoms combined with another element. This basic chemistry of oxygen will be helpful to consider as we delve into the biology and health components of oxygen.

At standard temperature and pressure, two oxygen atoms will bind covalently (a chemical bond involving shared electrons forming electron pairs between atoms) to form dioxygen, a colorless and odorless diatomic gas with the chemical formula O2.

Oxygen is also the most abundant element in Earth’s crust, and the third-most abundant element in the universe after hydrogen and helium. Dioxygen gas currently constitutes 20.95% molar fraction of the Earth’s atmosphere, though this has changed considerably over long periods of time in Earth’s history. Oxygen makes up almost half of the Earth’s crust in the form of various oxides such as water, carbon dioxide, iron oxides and silicates.

Genesis of Oxygen

Although we take the presence of oxygen for granted today and couldn’t exist without it, there was a time on Earth of about 2 billion prior to the existence of atmospheric oxygen. Around 2.33 billion years ago, oxygen began to accumulate in the Earth’s atmosphere (2) , and an event known as the ‘The Great Oxygenation’, which altered the trajectory of biological evolution, occured. This increase of oxygen in the atmosphere is hypothesized to have allowed for the generation of complex, multicellular lifeforms as demonstrated by a McGill University study.

Where did this oxygen come from? All those eons ago, the interaction of the nuclear furnace in the sky, our Sun, with bacteria began generating oxygen through the process of photosynthesis, which is the ability to release oxygen from water using the energy of sunlight. The first atmospheric oxygen came from the metabolism of microorganisms, the cyanobacteria, that used photosynthesis. Interestingly, the oxygen produced by these organisms was an unwanted by‐product of their metabolic processes and needed to be discarded for the bacteria to survive. When a major increase of oxygen concentration in the atmosphere occurred some 2 billion years ago, and the partial pressure of oxygen in the air rose to perhaps 200 mmHg, this Great Oxidation Event as it was called, was a death sentence for the large population of anaerobic animals for whom oxygen was toxic (3) . Today much of the oxygen in the atmosphere comes from photosynthesis in microorganisms, including the cyanobacteria, and the recently discovered Prochlorococcus, that discard this unwanted by‐product (4) . The result is that the partial pressure of oxygen (PO2) in our atmosphere at sea level remains nearly constant at about 150 mm Hg, although the factors responsible for this are not completely understood .

As our primary interest in this article is the role of oxygen in modern homo sapiens, suffice it to say that over the long arc of biological evolution, oxygen became an essential component of eukaryotic organisms (of which humans are one).

(2) Genming Luo et al.,Rapid oxygenation of Earth’s atmosphere 2.33 billion years ago.Sci. Adv.2,e1600134(2016).DOI:10.1126/sciadv.1600134

(3) West J. B. (2022). The strange history of atmospheric oxygen. Physiological reports, 10(6), e15214. https://doi.org/10.14814/phy2.15214

(4) West J. B. (2022). The strange history of atmospheric oxygen. Physiological reports, 10(6), e15214. https://doi.org/10.14814/phy2.15214

Biology of Oxygen

The world record breath-hold is 24 minutes 37.36 seconds – a remarkable feat though certainly not recommended to attempt surpassing unless one is highly trained in the art and science of breath holding.

Oxygen is a critical component of human life and biology, and we couldn’t survive without it for more than a short period. For most, going without oxygen for more than around 4 minutes can lead to potential brain damage. As biological evolution unfolded, oxygen became a critical component of life at the most foundational level – the cell. To reach cells, oxygen first travels through the pathway of respiration.

Respiration

Although the primary focus will be on how oxygen levels within the cell and cellular organelles impact health and can be adjusted for specific health outcomes, it is also helpful to understand how oxygen makes its way from the air around us and into the smallest recesses of cellular structures.

Components of the respiratory system include the airway, which consists of the following components:

Mouth
Nose and linked air passages (nasal cavity and  sinuses)
Larynx (voice box)
Trachea (windpipe)
Bronchial tubes, or bronchi, and their branches
Smaller tubes called bronchioles that branch off the bronchial tubes

Air first enters your body through your nose or mouth, which moistens and warms the air since cold, dry air can irritate your lungs. The air then travels past your voice box and down your windpipe. Rings of tough tissue, called cartilage, acts as a support to keep the bronchial tubes open.

Inside your lungs, the bronchial tubes branch into thousands of thinner tubes called bronchioles. The bronchioles end in clusters of tiny air sacs called alveoli.

The lungs contain around 150 million alveoli which are elastic and can change size and shape easily. Alveoli can easily expand and contract as their insides are coated with a surfactant, which reduces the work it takes to breathe by helping the lungs inflate more easily with inhalations. This substance also prevents the lungs from collapsing with exhalations.

The alveoli are comprised of a mesh of tiny blood vessels known as capillaries, which connect to a network of arteries and veins that move blood through your body. Once in the bloodstream, oxygen is carried in two forms:

Oxygen dissolved in plasma
Oxygen bound to hemoglobin (Hgb)

The amount of oxygen carried by the blood is known as the total oxygen content (CaO2). Only a small portion of oxygen is dissolved in plasma, and the majority is carried bound to Hgb due to its high affinity for oxygen – one gram of Hgb can carry 1.39 mL of oxygen.

Oxygen then moves into cells throughout the body by a process known as ‘simple diffusion’, which allows the 02 molecule to move easily through cell membranes. With simple diffusion, atoms, ions, or molecules cross directly through a semipermeable membrane, such as the cell membrane. Primary features of simple diffusion are occurrence of diffusion down the concentration gradient through a semipermeable membrane. This pathway requires no protein transporters to assist the crossing of molecules across the cell membrane. Once the 02 molecule has moved into the cell, it enters the process of cellular respiration. A basic understanding of cellular respiration is helpful in order to understand how applications such as intentional hypoxic training function.

(5) West J. B. (2022). The strange history of atmospheric oxygen. Physiological reports, 10(6), e15214. https://doi.org/10.14814/phy2.15214

Cellular Respiration: Oxygen and the Krebs Cycle

The Krebs/Citric Acid Cycle

The Krebs cycle is an intricate and complex process that occurs inside the mitochondria of eukaryotic organisms, such as humans. Although each detail of this cycle is beyond the scope of this article, a basic understanding of oxygen’s role in this core biological process of energy production provides insight into oxygen metabolism and cellular impacts of hypoxia.

Although oxygen isn’t a direct component of the Krebs cycle, it is needed to initiate the process through the mechanism of aerobic glycolysis. Although anerobic glycolysis is the principle means of energy production in some organisms, such as anerobic bacteria, aerobic glycolysis is the primary means of energy production in humans. When the human body is exposed to low-oxygen states, it is also able to enter a state of anaerobic energy production, a concept that will be relevant as we move forward with the exploration of hypoxic hormesis.

Anaerobic glycolysis is the transformation of glucose to lactate when limited amounts of oxygen are available. This occurs in health such as in exercising and in disease such as in sepsis and hemorrhagic shock and provides energy for short periods ranging from 10 seconds to 2 minutes. During this time, it can augment the energy produced by aerobic metabolism but is limited by the buildup of lactate and is difficult to maintain. The anaerobic glycolysis (lactic acid) system is dominant from about 10–30 seconds during a maximal effort and produces only two ATP molecules per glucose molecule, or about 5% of glucose’s energy potential, which is 38 ATP molecules.

Cellular Aerobic Glycolysis

In the presence of cellular oxygen, pyruvate is generated, and a subsequent compound known as acetyl CoA delivers its acetyl group to a four-carbon molecule, oxaloacetate, to form citrate, a six-carbon molecule with three carboxyl groups; this pathway will harvest the remainder of the extractable energy from what began as a glucose molecule as part of the citric acid cycle.

A broad overview of the citric acid cycle includes the following eight steps:

Step 1: the formation of citrate from oxaloacetate and acetyl-CoA by the action of citrate synthase. This step is exergonic and releases about -31.4 kJ/mol of energy.
Step 2, the citrate is converted into an isomer molecule called isocitrate by the action of aconitase. This step is endergonic and requires an input of about 6.3 kJ/mol of energy. This conversion helps prepare the molecule for the first decarboxylation step.
Step 3, isocitrate undergoes an oxidative decarboxylation reaction in which the enzyme isocitrate dehydrogenase creates alpha-ketoglutarate. This produces an NADH molecule and releases a carbon dioxide.
Step 4 is also an oxidative decarboxylation step that is catalyzed by a different enzyme called the alpha-ketolgutarate dehydrogenase complex. This step produces succinyl CoA, generates another NADH molecule and releases a carbon dioxide.
Step 5, succinyl CoA synthetase transforms the succinyl CoA into a succinate; in the process, a GDP molecule is transformed into a GTP.
Step 6, the succinate is transformed into a fumarate by the action of succinyl dehydrogenase, an enzyme that is bound to the inner mitochondrial membrane.
Step 7: fumarate is transformed into the L-isomer of malate via a hydration reaction and by the action of the enzyme fumarase.
Step 8: of the citric acid cycle, the fumarate is converted into oxaloacete by malate dehydrogenase. This forms yet another NADH molecule. In total, a single acetyl CoA that moves into the citric acid cycle produces three NADH molecules, a single FADH2 molecule and a single GTP or ATP molecule.

An additional means of energy production is through the generation of ketones. When sufficient ketones are generated, it is known as a ketogenic state, and this will be explored further in part 2 of this series.

(6) Williams, M. S., & Turos, E. (2021). The Chemistry of the Ketogenic Diet: Updates and Opportunities in Organic Synthesis. International journal of molecular sciences, 22(10), 5230. https://doi.org/10.3390/ijms22105230

Conclusion

Oxygen is an extraordinarily ancient molecule intricately involved in the evolutionary process of biological organisms on Earth. As one of the most abundant components of both life on Earth and of the matter comprising the universe itself, 02 intertwines intimately with the most fundamental aspects of human biology.

In part 1 of this series, the following components regarding oxygen have been reviewed:

The discovery of oxygen
The chemical structure of oxygen
The genesis of oxygen
Fundamentals of oxygen and cellular respiration

In part 2 of this series, the following components of oxygen will be explored:

Ketones and cellular respiration
Oxygen and free radicals
The impact of oxidative stress on health

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