What does the human body use oxygen for besides the final electron acceptor in the electron transport chain?

Question

My biology teachers never explained why animals need to breathe oxygen, just that we organisms die if we don't get oxygen for too long. Maybe one of them happened to mention that its used to make ATP. Now in my AP Biology class we finally learned the specifics of how oxygen is used in the electron transport chain due to its high electronegativity. But I assume this probably isn't the only reason we need oxygen.

What other purposes does the oxygen we take in through respiration serve? Does oxygen deprivation result in death just due to the halting of ATP production, or is there some other reason as well? What percentage of the oxygen we take in through respiration is expelled later through the breath as carbon dioxide?

Answer 1

Oxygen is actually highly toxic to cells and organisms – reactive oxygen species cause oxidative stress, essentially cell damage and contributing to cell ageing. A lot of anaerobic organisms have never learned to cope with this and die almost immediately when exposed to oxygen. One classical example of this is C. botulinum.

Oxygen is incorporated in several molecules in the cell (for instance riboses and certain amino acids) but as far as I know, all of this comes into the cell as metabolic products, not in the form of pure oxygen.

The oxygen ($\ce{O2}$) we breathe is completely used up during aerobic respiration. The stoichiometry of this is given by the following simplified equation:

$$\ce{C_6H12O6 + 6 O2 -> 6 CO2 + 6 H2O + heat}$$

WYSIWYG’s answer goes into more detail.

Answer 2

Superoxide, O₂⁻ is created by the immune system in phagocytes (including neutrophils, monocytes, macrophages, dendritic cells, and mast cells) which use NADPH oxidase to produce it from O₂ for use against invading microorganisms. However, under normal conditions, the mitochondrial electron transport chain is a major source of O₂⁻, converting up to perhaps 5% of O₂ to superoxide. [1]

As a side note, there are two sides to this coin. While this is a useful tool against microorganisms, the formation of the reactive oxygen species has been incriminated in autoimmune reactions and diabetes (type 1). [2]

[1] Packer L, Ed. Methods in Enzymology, Volume 349. San Diego, Calif: Academic Press; 2002

[2] Thayer TC, Delano M, et al. (2011) Superoxide production by macrophages and T cells is critical for the induction of autoreactivity and type 1 diabetes,60(8), 2144-51.

Answer 3

You probably know by now that cytochrome c oxidase, the last complex of the electron transport chain, belongs to a class of enzymes called oxidoreductases, that use oxygen atoms as electron acceptors. One type of oxidoreductases are oxidases, enzymes that (at least in theory [1]) use molecular oxygen--O₂, like in air--as their electron acceptor. From what I know, however, sometimes that isn't the case: xanthine oxidase, that converts xanthine to uric acid, gets its oxygen atoms from water [2]. Examples of the "true" oxidases include L-amino-acid oxidase and cytochrome P450 (aka. CYP family).

Despite cytochrome P450 being a numerous and important enzyme family, responsible for most of known drugs metabolism and some essential lipids transformations, it probably consumes only a fraction of oxygen that animals breathe in. I wasn't able to find any estimations, but would be surprised if it was more than perhaps 0,1%.

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[1] Introduction to EC1 class

[2] Metz, S. & Thiel, W. A Combined QM/MM Study on the Reductive Half-Reaction of Xanthine Oxidase: Substrate Orientation and Mechanism. J. Am. Chem. Soc. 2009, 131, 14885–14902, PMID: 20050623.

Answer 4

The overwhelming use of oxygen is to provide us (in combination with food) with energy. We have a great need for energy in our cells, which is why we have these lungs, diaphragms, red blood cells, etc.; they assure we get the oxygen to obtain the energy (via the electron transport chain).

The overall metabolism of glucose (C₆H₁₂O₆) is a representative reaction:

 C6H12O6 + 6 O2 --> 6 CO2 + 6 H2O + energy

You can see that just as much oxygen goes out as gaseous CO₂ as came in as gaseous oxygen (O₂).

The energy is temporarily kept in the form of the phosphate bond in ATP molecules so that it can be shuttled around the cell to the multitude of cellular processes that need energy.

Energy is so essential to the cellular processes that maintain animal cells that lack of that energy, which results quickly when there is oxygen deprivation, soon causes irreversible damage and death.

Answer 5

Another small addition

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There is class of oxidoreductases called oxygenases which incorporate molecular oxygen into the substrates and not just use it as an electron acceptor like in oxidases (note that the terminal enzyme in ETC is an oxidase and there are other such oxidases). In other words, oxygen is not a cofactor but a co-substrate. Oxygenases are further classified into dioxygenases and monooxygenases which incorporate two oxygen atoms and one oxygen atom respectively. Examples:

• Cytochrome P450 family (monooxygenease): involved in detoxification of xenobiotics
• Cyclooxygenase (dioxygenase): involved in production of prostaglandins which are involved in pain and inflammation. Many NSAID painkillers like aspirin, paracetamol and ibuprofen target cyclooxygenase-2 (COX2)
• Lipoxygenase (dioxygenase): Involved in production of leukotrienes which are involved in inflammation.
• Monoamine oxidase (monooxygenase): Involved in catabolism of neurotransmitters such as epinephrine, norepinephrine and dopamine.

Does oxygen deprivation result in death just due to the halting of ATP production, or is there some other reason as well?

Death predominantly occurs because of halt in ATP production. Some cells such as neurons (and also perhaps cardiac muscles) are highly sensitive to loss of oxygen (for energy requirements) and clinical death because of hypoxia usually occurs because of loss basic brain function.

What percentage of the oxygen we take in through respiration is expelled later through the breath as carbon dioxide?

As already mentioned, it is said that there is a rough 1:1 ratio of CO₂ production and O₂ consumption. However, as indicated in a comment by CurtF, O₂ does not form CO₂; it forms water in the last reaction of ETC. CO₂ is produced in other reactions of Krebs cycle.

Glycolysis produces 32 molecules of ATP for 1 molecule of glucose via ETC (see here). There are three complexes in ETC and the third is dependent on oxygen; so you can assume that 1/2 a molecule of O₂ consumed for production of 3 ATP molecules. Therefore 32 molecules of ATP would consume 4 molecules of O₂. Seems like there is a 1:1 ratio of CO₂ production and O₂ consumption.

We can see it like this:

FADH₂ enters ETC at the second complex whereas NADH enters at the first. We can say that as long as NADH is present FADH₂ would not require an extra oxygen.

An NADH or a FADH₂ molecule would require 1/2 molecule of O₂. There are 8 molecules of NADH and 2 molecules of FADH₂ produced during glycolysis+krebs cycle which would require 10/2 = 5 molecules of O₂. Glycolysis produces 4 molecules of CO₂ during krebs cycle.

However, 2 cytosolic NADH molecules require 2 ATPs (in other words another NADH molecule) to be transported to mitochondria. So the net effect may be actually close to 1:1 O₂:CO₂.

Another factor to keep in consideration is that the three complexes do not actually produce ATP; they just pump proton to create a chemical potential. The F₀F₁-ATP synthase would probably work only after a threshold of H⁺ potential is established. The 1 ATP molecule per complex is most likely the mean value and not exactly what really happens per reaction.