Talk:Cytochrome c oxidase

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Wiki Education Foundation-supported course assignment

This article is or was the subject of a Wiki Education Foundation-supported course assignment. Further details are available on the course page. Student editor(s): Soniaiyengar7.

Above undated message substituted from Template:Dashboard.wikiedu.org assignment by PrimeBOT (talk) 18:55, 16 January 2022 (UTC)[reply]

Edits

Hello Wiki Community,

I have a few suggestions for revising this article, and would appreciate any feedback or direction you can give me in doing so!

I would like to expand two sections of the article that appear unusually brief: inhibition and histochemistry. A deeper understanding of both is vital to a larger understanding of the physiological significance of Complex IV.

With regards to the inhibition component of the article, I would like to make the following edits or changes. I would first expand upon each inhibitor mentioned in the first sentence: cyanide, azide, sulfide, and carbon monoxide, with the addition of nitric oxide. I would also like to discuss the effects of interplay of two different competitive inhibitors on COX (i.e. the reduced inhibition of cyanide ion on COX with the addition of exogenous nitric oxide at high concentrations of cyanide), and list two to three examples of the effects. The similarity of all four can also be elaborated on in a short sentence after the first (before going into each inhibitor specifically), with a focus on pH sensitivity (i.e. azide) in physiological conditions, and the effects of pH sensitivity on inhibitor binding. The biochemical relationship between inhibitor binding and oxidation with enzymatic changes can also be expanded upon, and specifically changes to the binuclear center and oxidation states of metal ions upon electron transfer can be discussed within respect to each specific inhibitor. For azide, I would also like to mention the two methods of determining azide inhibition effects on COX, in-vitro (extensively studied in the late twentieth to early twenty-first century), and in-vivo induction (more recent). Lastly, ATP inhibition of COX and the overall significance of understanding COX inhibition can be discussed.

In terms of the histochemistry of COX, I would first like to discuss the significance of a histochemical analysis of COX activity (without too much overlap from the clinical significance section), specifically focusing on the relationship of mtDNA mutations to accelerated aging and the development of age-related disorders. A brief overview of all animal models utilized in histochemical examination of COX will be listed, as well as the observations made and significance of comparison across multiple animal models. A small paragraph on common protocols and methods of histochemical analysis of COX will conclude this section.

A bibliography is listed below as well as on my user page. Many of my sources are primary literature in the form of articles. Thank you, any feedback is immensely appreciated, this is a topic of interest and I would like to learn as much as I can!

References:

Leavesley HB, Li L, Prabhakaran K, Borowitz JL, and Isom GE (September 2007). "Interaction of cyanide and nitric oxide with cytochrome c oxidase: Implications for Acute Cyanide Toxicity". Toxicological Sciences, Oxford Journals 101 (1): 101-11. doi: 10.1093/toxsci/kfm254.
Wilson MT, Antonini G, Malatesta F, Sarti P, and Brunori M (July 1994). "Probing the oxygen binding site of cytochrome c oxidase by cyanide". The Journal of Biological Chemistry 269 (39): 24114-9. PMID 7929065.
Nicholls P, Marshall DC, Cooper CE, and Wilson MT (October 2013). "Sulfide inhibition of and metabolism by cytochrome c oxidase". Biochemical Society Transactions 41 (5): 1312-6. doi:10.1042/BST20130070. PMID 24059525.
Hevner RF and Wong-Riley MTT (November 1989). "Brain cytochrome oxidase: Purification, antibody production, and immunohistochemical/histochemical correlations in the CNS". The Journal of Neuroscience 9 (11): 3884-98. PMID 2555458.
Bennett MC, Mlady GW, Kwon YH, and Rose GM (June 1996). "Chronic in vivo sodium azide infusion induces selective and stable inhibition of cytochrome c oxidase". The Journal of Neurochemistry 66(6): 2606-11. PMID 8632188.

Soniaiyengar7 (talk) 03:48, 5 May 2016 (UTC)[reply]

Untitled

This sentence (as of 2/8/2007) is not accurate and probably should be rewritten.

"Cyanide, sulfide, azide and carbon monoxide all bind to Cytochrome c Oxidase, thus inhibiting the protein from functioning which results in chemical suffocation of cells."

Cytochrome c oxididase is a ferric heme protein in the resting state. While cyanide binds tightly to ferric proteins, carbon monoxide binds tightly to ferrous heme proteins. While the mechanism of action of CO is to suffocate people by virtue of its action on ferrous heme oxygen transport proteins (i.e. hemoglobin and myoglobin), it's not a large player at the oxidase level.

Cyanide and those agents which bind tightly to CCO cause an immediate halt of aerobic respiration, and because of the buildup of chemical intermediates, will eventually cause the cessation of aerobic and anaerobic processes.

I'm complaining because there is a constant confusion among lay people (and even scientists not familiar with the area) about the mechanism of toxicity in vivo of CO and CN-. They are not the same and people trying to make this topic easier may in fact be obscuring real facts.

========

"There are 2 molecules water gained in the Cytochrome C oxidase catalized reaction and not only one!"

Ions are usually written with the number first, then the polarity of charge, i.e. Fe2+ or Fe3+, rather than Fe+2/+3 as is written here. Man I gotta get around to learnin LaTeX 203.129.49.176 20:21, 17 May 2006 (UTC)[reply]

========

This traces the energy, electrons, and photons when light reverses the respiratory action and act as a fuel cell to generate 4H+ and O2 from H20 to slow the krebs cycle when animals are in bright sunlight.

Normal operation of 3rd pump (CcO): electrons are brought in through the prior pumps that received e- energy from the krebs cycle. At the active pumping site of CcO, 2e- are bought in to attract 2H+ in tunnel A and 2H+ in tunnel B. O2 is spread apart in the iron-based active site so that the 2e- and 2H+ of tunnel B react with one oxygen to form H20. This releases energy that boots the 2H+ in tunnel A on up the gradient to the outside of the membrane. Since the 2e- that were being used to hold the 2H+ in place are now inside the H2O, there is nothing holding 2H+ in the active area. The exact mechanism of this second step of booting up the gradient is not known. Another 2e- are waiting in the wings (a 2 copper site) to react with the other oxygen in the same manner with the same result (H2O and a booting of another 2H+ upwards). Summary: O2+4e+8H => H2O + H2O + 4H+ where 4H+ is the energy gradient increase.

Instead of forming H2O to use electrons and release energy, let's run it in reverse and let light energy breaks apart H2O to release electrons. There are 5 metal atoms in this protien that do everything. 3 are at the active site, 2 irons and a copper. Two more coopers are at a "staging" area for bringing electrons in from the "electron food chain". Only the coppers absorb light strongly in the near-infrared, which can penetrate blood and water. In fact, it appears hemoglobin evolved to specifically allow these frequencies through since they were already being used for energy in bacteria. The copper at the 2-iron main reaction (pumping) site absorbs strongest at 670 nm (red) which is a higher energy level than what the other two coppers absorb at near-infrared). 1/4 or so of the red photon energy is absorbed and splits H2O (fuel cell!) to generate the 2e- that are needed at the reaction site to pull in 2H+ up tunnel A. This creates 2H+ in tunnel "B" from the H2O and the split oxygen is being held in one of the irons. Then the 2e- combine with the 2H+ in tunnel B and the oxygen held in the iron to recreate the H20 which releases the rest of the light energy the system had temporarily stored which boots the tunnel A 2H+ on up the gradient. So no electrons or ANYTHING ELSE comes in or out of the system, but 4H+ are delivered up the gradient thanks to light energy. The other 2 coppers that are outside of the 2 active iron site may also get into the act by absorbing light to push 2 more temporary electrons against an H+ gradient to bring them to the active site, but i don't know if it's necessary for the light-pumping. These wold also be cycled back and forth without using anything but light energy.

Therefore this cyctochrome c oxidase is not merely a respiration-based pump. Its organization and use of copper is not merely an evolutionary left over from bacteria that used light. It is an active photoreceptor providing possibly up to 20% of the energy to people laying out in the sun. Smaller animals with little hair will see the greatest benefit since the light only penetrate a few centimeters in the windo between the absorption of blood and water.

But the story isn't finished: When light has pushed a lot of H+ outside the mitochondrial membrane, the H+ gradient is stronger and there is an increased pull towards the 2 staging coppers to pull e- out of the reaction site. This prevents the 2e- from absorbing back into the H2O which leaves 2H+ in tunnel B. O2 is created if it occurs twice (2H2O + 2 red photons => 4H+, 4e-, and O2). The 2e- in the 2-copper staging area absorbs light energy which might be used to jolt e- back into cytochrome c to be used for the previous pumps to act in reverse, as they are known to do. As the H+ gradient increases, the first 2 pumps that provided e- to our 3rd pump (under food conditions) start wanting to act in reverse (they are basically "passive" pumps known to act equally well in reverse). By providing the 2e- necessary, these pumps will recreate NADH and FADH food energy and deplete some of the H+ gradient and recreate NADH or FADH. The other two pumps do not absorb light energy. CcO is blue in color like some bacteria as a result of the coppers that are absorbing blue's opposing color, red (and infrared).

The increased H+ gradient creates more ATP, and the reversed pumps create more NADH and FADH. This halts the krebs cycle which increases the available pyruvate and therefore glucose so that energy stores are increased for time periods longer than ATP.

Only in recent years has the functioning of CcO been understood well enough to show how it could be run in reverse.

From a PhD thesis:

"Tyrosine residues in photosynthetic plants ...have been shown to ... oxidize H2O to O2 which is the reverse of CcO. Therefore [this tyrosine residue at the center of CcO] is presumed to play an important role in [here comes the blah blah blah that just misses the "reversibility" point] in electron redistribution and electron transfer at the active site" There it is, right under their nose, screaming at them "i am capable of photosythesis". A single red photon hitting the copper that's right next to this tyrosine residue is all that's needed to split the H2O to O2. Right before that paragraph she wrote that the tyrosine residue is "highly conservative" which means "easily reversible"

Scott

Terminal Electron Acceptor

Perhaps I'm wrong, but I've been educated that the terminal electron acceptor is oxygen (or another inorganic molecule such as Fe3+, NO3-, etc.), and that cytochrome oxidase catalyzes this reaction (not that cytochrome oxidase IS the terminal electron acceptor). In the sense that cytochrome oxidase is the final protein in the ETC to have the electron it is the terminal acceptor, but it is merely passing it off to it's final acceptor, oxygen. Therefore, I think that calling it the terminal electron acceptor is misleading and this should be reworded.

Good point. Cytochrome C oxidase it is the final protein which accepts electrons in the electron transfer chain, but the terminal electron acceptor (in the chemical sense) is oxygen. —The preceding unsigned comment was added by Zephyris (talk • contribs) 10:37, 12 February 2007 (UTC).[reply]

Competitive inhibitors

Concerning the following extract: "Cyanide, sulfide, azide, and carbon monoxide[5] all bind to cytochrome c oxidase, thus competitively inhibiting the protein from functioning..." I wanted to clarify whether Cyanide was a competitive or a non-competitive inhibitor. The source given only concerns Carbon Monoxide, and some other sources (Examples: 1, 2 and 3) call Cyanide non-competetive. -- Mixy1 —Preceding undated comment added 19:53, 10 January 2013 (UTC)[reply]

I was also taught that CN- is a non-competitive COX inhibitor. I think Mixy1's refs are sufficient to establish that, and a quick search doesn't throw up any recent research to the contrary, so I've made the change. I played safe by also removing the phrase about preventing binding of oxygen. Pastychomper (talk) 13:12, 20 March 2018 (UTC)[reply]

They need to point out that COX also refers to Cyclo-oxygenase

I am no expert in the field, but the medical and drug literature commonly refer to COX as cyclo-oxygenase, a totally different system. So, many readers might make the mistake that this discussion of COX applies to the other system. There should be a clear statement in this article that points out the difference. — Preceding unsigned comment added by 172.56.21.235 (talk) 08:00, 16 April 2018 (UTC)[reply]

Assessment comment

The comment(s) below were originally left at Talk:Cytochrome c oxidase/Comments, and are posted here for posterity. Following several discussions in past years, these subpages are now deprecated. The comments may be irrelevant or outdated; if so, please feel free to remove this section.

I have added a crucial reference to the Science paper giving the crystal structure of bovine cytochrome oxidase, and added details to the mechanism of electron transfer and the cycle which reduces oxygen to two waters. I do believe that this article should incorporate some of the details from the article on COX biogenesis, and then the latter deleted. I am not up on the details of this other article and will leave it up to someone else to decide what to move over to this article. GraybeardBiochemist 23:52, 28 October 2007 (UTC)[reply]

Last edited at 04:23, 23 March 2008 (UTC). Substituted at 12:38, 29 April 2016 (UTC)

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Hello everyone,

I have been looking for more up to date articles to supplement and enhance the article. Most of the ones referenced and the ones I am finding on my own seem to be from the 70s and 90s. Has anyone found more recent research that could help this article? Cmiller02 (talk) 02:47, 28 January 2018 (UTC)[reply]

What membrane?

The enzyme cytochrome c oxidase ... is a large transmembrane protein complex found in bacteria, archaea, and in eukaryotes in their mitochondria.
It is the last enzyme in the respiratory electron transport chain of cells located in the membrane.

The mitochondrial membrane in eukaryotes, but some other (unspecified) membrane otherwise? "I'll take 'membranes of archaea' for 500, Alex." — MaxEnt 13:03, 22 September 2018 (UTC)[reply]

cytochrome c oxidase 1 and DNA barcoding

Seems like there should be a link to DNA barcoding since COX1 is the barcode region for animals. JuanTamad (talk)