Why oxygen is so critical to our survival?

[mktsgm]

Is oxygen useful in only in the production of ATP with the cells (aerobic cellular respiration)?

If so, why one should die within second if the oxygen supply is cut off?

Why oxygen is so critical to our survival?

 

[dartleader]

You are correct that O2 is used in the Krebs cycle to produce ATP, our body's main source of fuel.

The brain cannot store ATP, O2, or Glucose, for that matter; without a constant supply, the brain will quickly shut down less critical functions (ie: consciousness, executive decision making) in order to preserve critical functions (ie: Breathing, Heartbeat).

Without a quick restoration of an O2 supply, death is inevitable.

 

[Astronuc]

If so, why one should die within second if the oxygen supply is cut off?

It takes more than a second, and more like minutes. The brain needs oxygen to function, as does the rest of the body.

Oxygen plays a key role in cells, particularly brain and nerve cells.

See - http://www.phschool.com/science/biology_place/biocoach/cellresp/overview.html
Oxidative phosphorylation via the electon transport chain is carried out on the inner mitochondrial membrane.
In the absence of oxygen, respiration consists of two metabolic pathways: glycolysis and fermentation. Both of these occur in the cytosol.

https://en.wikipedia.org/wiki/Cellular_respiration
https://en.wikipedia.org/wiki/Oxidative_phosphorylation

See also - http://www.strokecenter.org/profess...al-function-importance-of-oxygen-and-glucose/

The transient change in voltage induced by the action potential is determined by the concentration of ions on either side of the cell membrane. Maintaining these ionic gradients is an energy-consuming process that requires a constant supply of glucose and oxygen to the neuron.

Sugar for the brain: the role of glucose in physiological and pathological brain function
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3900881/
"The mammalian brain depends on glucose as its main source of energy." I think implicit in this statement is the need for oxygen which is used to oxidize glucose.

From https://www.tamu.edu/faculty/bmiles/lectures/integration.pdf

The muscles account for 50% of the total oxygen consumption in the resting state, but during vigorous exercise the muscles account for 90% of the oxygen consumption. After a period of intense muscular activity, heavy breathing occurs for some time. Much of the oxygen is used for oxidative phosphorylation to restore and ATP and phosphocreatine levels.

 

[mktsgm]

Thanks. I meant... seconds... not second.

 

[DiracPool]

If so, why one should die within second if the oxygen supply is cut off?

As Astronuc pointed out, it takes minutes, not seconds, to die from "anoxia" or "hypoxia." In the brain, you have two principle cell types, neurons and glial cells. As for the glial cells, "astrocytes" are the most common form in the cerebral cortex. The glial cells are supporting structures for the neurons (which do the principal information processing work). However, the glial cells are essential to the effective operation of the brain. They provide an essential energy component to the neurons through such means as "glutamate cycling" and the astrocyte-neuron lactate shuttle (ANLS), and they also have these little feet (how cute) that wrap around capillaries in the brain and cause those capillaries to expand and increase their blood flow in times of need. These sorts of duties of the supporting glia cells make their role indispensable to the larger effort that the brain makes to keep you alive.

As far as the oxygen, the Krebs cycle in the mitichondria is most effectively run in the presence of O2 through oxidative phosphorilization, again, as Astronuc pointed out. In the manner of the respiration of the cell, every eukaryotic cell, which obviously includes neurons, glucose first runs through the glycolytic cycle (glycolysis) which produces pyruvate, which then is put through the Krebs cycle (aka the tricarbolytic acid cycle and citric acid cycle). The end result is the production of ATP.

Why is ATP important for the functioning of neurons? Well, ATP is instrumental in running the sodium-potassium pump of neurons. This pump maintains the resting-membrane potential that allows the neurons to produce action potentials or "spikes." If you compromise the integrity of the pump to maintain that resting membrane potential in a timely fashion, you're going to have big problems.

How does this work, you might ask? Well, I'm too lazy to look it up right now, but I think one ATP molecule will effectively transport two sodium ions out of the cell and transport three potassium ions into the cell. This works against a potential electrical voltage gradient which is why ATP is needed, ATP provides the energy through the breaking of a bond of the phosphate group on the molecule which strips it of that group and turns it into ADP, at which point it goes back into the Krebs cycle.

Getting back to glycolytic metabolism, I think that when a glucose molecule runs through this metabolic cycle in the presence of oxygen, it produces something on the order of 38 ATP molecules. I'm not exactly sure on that number, though, so don't quote me (look it up). The kicker, though, is that pyruvate can also also produce ATP in an anerobic environment (w/o oxygen). Pretty clever, huh? The rub, though, is that I think one pyruvate molecule only produces two ATP molecules through this anaerobic process. So, this is much less efficient than the aerobic oxidative phosphorylation process and the reason why you have about 5 minutes to live if you are drowning...

 

[atyy]

Although it is true that maintaining the ionic concentration gradient across the neuronal membrane requires energy, I doubt that non-maintenance of ionic concentration is the main reason for quick brain damage when one is deprived of oxygen.

If the sodium potassium pump which maintains the gradient is poisoned, I think one only gets a 6-10 mV decrease in the magnitude of the potential difference across the membrane (out of a starting potential difference of 70 mV). If one poisons only the sodium potassium pump, it usually takes hours (not minutes) for the potential difference to run down to an unhealthy level.

I've extracted from the paper below the most common hypothesis about why neurons die (glutamate poisoning) after oxygen deprivation. A depolarization from -70 mV to -60 mV will cause neurons to spike more, and release more glutamate at synapses. However, it is unclear whether glutamate release from synapses is what kills neurons. It may be glutamate released from extrasynaptic locations that is much more important.

https://www.ncbi.nlm.nih.gov/pubmed/20670828
Neuron. 2010 Jul 29;67(2):181-98. doi: 10.1016/j.neuron.2010.07.002.
The science of stroke: mechanisms in search of treatments.
Moskowitz MA, Lo EH, Iadecola C.
"Excitotoxicity and calcium overload are major factors contributing to the early stages of ischemic cell death. The canonical pathway asserts that glutamate, the most abundant neurotransmitter, accumulates into the extracellular space as a consequence of energy and ion pump failure, as well as failure of reuptake mechanisms (Choi and Rothman, 1990). The glutamate overload leads to prolonged stimulation of AMPA and NMDA ionotropic receptor subtypes to dramatically enhance the influx of calcium, sodium, and water into neurons. Massive calcium influx activates catabolic processes mediated by proteases, lipases, and nucleases (Ankarcrona et al., 1995). In addition, activation of nNOS, PLA2, and other Ca2+-dependent enzymes leads to production of NO, arachidonic acid metabolites, and superoxide, which act as additional triggers of cell death (Dirnagl et al., 1999, Lo et al., 2003). For these and other reasons, oxidative phosphorylation becomes uncoupled, leading to further ATP depletion, ROS production, and release of stored Ca2+ from mitochondria, further accelerating a series of catastrophic events that lead to acute cell death."

https://www.ncbi.nlm.nih.gov/pubmed/10411944
Proc Natl Acad Sci U S A. 1999 Jul 20;96(15):8733-8.
Inhibition of uptake unmasks rapid extracellular turnover of glutamate of nonvesicular origin.
Jabaudon D, Shimamoto K, Yasuda-Kamatani Y, Scanziani M, Gähwiler BH, Gerber U.
"These results show that under basal conditions, the activity of glutamate transporters compensates for the continuous, nonvesicular release of glutamate from the intracellular compartment. As a consequence, acute disruption of transporter activity immediately results in significant accumulation of extracellular glutamate."

https://www.ncbi.nlm.nih.gov/pubmed/10805815
Proc Natl Acad Sci U S A. 2000 May 9;97(10):5610-5.
Acute decrease in net glutamate uptake during energy deprivation.
Jabaudon D, Scanziani M, Gähwiler BH, Gerber U.
"The extracellular glutamate concentration ([glu](o)) rises during cerebral ischemia, reaching levels capable of inducing delayed neuronal death. The mechanisms underlying this glutamate accumulation remain controversial. ... we demonstrate that energy deprivation decreases net glutamate uptake within 2-3 min and later promotes reverse glutamate transport. This process accounts for up to 50% of the glutamate accumulation during energy deprivation. Enhanced action potential-independent vesicular release also contributes to the increase in [glu](o), by approximately 50%, but only once glutamate uptake is inhibited. These results indicate that a significant rise in [glu](o) already occurs during the first minutes of energy deprivation and is the consequence of reduced uptake and increased vesicular and nonvesicular release of glutamate."

 

[mktsgm]

This glutamate is beating me. Honestly I don't understand it. Can someone interpret it for me in plain English?

Why one dies within minutes if deprived of oxygen?

Is it lack of something or sone toxins are in excess?

 

[rootone]

I think the disruption of the ATP and Krebs cycle would be the primary point of failure.
The body has had the equivalent of a power cut at an industrial plant, and pretty quickly all kinds secondary breakdowns can follow,

 

[DiracPool]

Why one dies within minutes if deprived of oxygen?

In plain English it's because the brain neurons stop functioning properly leading to brain death. Whether it's specifically a result of a compromising of the sodium-potassium pump as I described or from glutamate poisoning as atyy's alluded to may be more information than you want or need to know or that really may be definitely known in the medical literature. Also, there may be more than one way to die from anoxia/hypoxia (oxygen deprivation) than just brain death, e.g., a heart attack:

http://www.livestrong.com/article/106179-effects-lack-oxygen-brain/

"When the brain is not receiving enough oxygen, the heart rate will increase in an attempt to deliver more oxygen. If hypoxia is severe enough, the heart will be unable to keep up with the demand and may eventually fail, causing a heart attack."

Is it lack of something or sone toxins are in excess?

Yes, it is decisively a lack of oxygen . That may subsequently manifest in some sort of toxic effect that damages/kills neurons such as an excess of glutamate which, again, is discussed in the references of atyy's post #6.

The point I was trying to make in my post #5, though, is that the effects of hypoxia are going to precipitously lead to cognitive malfunction, coma, and death if the oxygen deprivation is not reversed. Again, maybe the compromising of the sodium-potassium pump is not the ultimate cause of brain death per se, but it is the principal causal factor. This is in the same sense that saying that a gunshot wound did not cause someones death, it was the subsequent sepsis, exsanguination, or heart attack that caused the death. However, in each case, the principal causal factor was the gunshot wound.

For example, in the hypoxia event we are talking about here, atyy noted that, initially, the compromising of the sodium-potassium pump may only effect the membrane potential by 10 mV or so. However, this would be enough to lower the resting membrane potential artificially close to the firing threshold whereby you would see a malicious excess in neuronal spike frequencies which may dump excess glutamate into the extracellular matrix causing toxic effects. However, this toxic effect which may indeed be the ultimate agent that kills the cells is a secondary effect from the primary causal effect which is the compromising of the efficacy of the sodium-potassium pump through the effect of oxygen deprivation on the production of ATP in the mitochondria via oxidative phosphorylation.

How does this work, you might ask? Well, I'm too lazy to look it up right now, but I think one ATP molecule will effectively transport two sodium ions out of the cell and transport three potassium ions into the cell. This works against a potential electrical voltage gradient which is why ATP is needed, ATP provides the energy through the breaking of a bond of the phosphate group on the molecule which strips it of that group and turns it into ADP, at which point it goes back into the Krebs cycle.

Btw, just to be complete. I had my figures reversed in this passage, it's actually 3 sodium ions out and 2 potassium ions in, not the other way around, which makes sense insofar as the membrane potential is being biased more negatively on the inside. I've included a little animation to demonstrate this which may also interest the OP as to how the Na-K pump works:

http://highered.mheducation.com/sit...ion__how_the_sodium_potassium_pump_works.html

 

[DiracPool]

I think the disruption of the ATP and Krebs cycle would be the primary point of failure.
The body has had the equivalent of a power cut at an industrial plant, and pretty quickly all kinds secondary breakdowns can follow,

Yeah, rootone beat me to the punch while I was crafting my long-winded explanation which basically says the same thing.

 

[snorkack]

Obviously any aerobe needs oxygen to produce ATP.
Why do human brain cells die when deprived of oxygen, and in a few minutes?
That the cells cannot function without energy supply is logical.
The reason seems to be that under hypoxic conditions, the biochemical processes go in wrong directions, and rapidly lead to conditions that are irreversible even if oxygen supply is later resumed.
But why does brain undergo such damage so fast?
For example, the blood supply to an arm can be shut off for several minutes, e. g. to measure blood pressure. The arm can still be moved voluntarily, and is not harmed.
Measuring blood pressure on the neck is not smart! Brain deprived of blood supply for a few minutes is liable to suffer damage, the way an arm does not.
The limb would eventually go numb in continued absence of blood flow. Even that is not at first permanent damage. I think that when blood flow to a limb is shut to stop arterial bleeding, it is not advised to last more than a hour or two.
Meaning that a limb car recover from lack of blood flow for an hour - even though the limb does contain nerves. A head cannot.
Why?

 

[mktsgm]

Can we say that we know death occurs after the deprivation of oxygen, but not sure why and how completely? Is it possible that some unknown mechanism may also be at work?

Or science has complete grasp of the pathology of hypoxia?

Is stopping of heart (arrest of blood circulation) and respiratory block (suffocation/smothering) are same in terms of oxygen deprivation?

 

[rootone]

It's not an unknown mechanism.
Mammals such as human beings depend on Oxygen to provide chemical energy which drives all of their metabolism.
No Oxygen = no energy; everything stops.

 

[snorkack]

It's not an unknown mechanism.
Mammals such as human beings depend on Oxygen to provide chemical energy which drives all of their metabolism.
No Oxygen = no energy; everything stops.

The problem is that everything does not stop.
If everything did stop, it could continue from the same place if and when oxygen ever comes back.

 

[rootone]

I guess that is more accurate, what I meant was that normal metabolism stops.
It is replaced by abnormal biochemistry, some of which causes permanent damage to organs.

 

[mktsgm]

I thank you all for the clarification. I have much to go on.

 

[atyy]

This glutamate is beating me. Honestly I don't understand it. Can someone interpret it for me in plain English?

Why one dies within minutes if deprived of oxygen?

Is it lack of something or sone toxins are in excess?

Glutamate is released by neurons to signal to other neurons. When one neuron receives glutamate from another neuron, it becomes more likely to release glutamate. That is part of healthy brain function. However, under hypoxia, glutamate increases in the extracellular fluid by abnormal mechanisms, as well as the normal mechanisms driven into an unhealthy positive feedback regime. Glutamate causes lots of calcium to enter neurons, which triggers cell death.

 

[rootone]

Oxygen is able to react with many other substances and energy is released as a result, usually as heat.
Oxygen does dissolve (in water) though not a lot, plants use that to help grow their roots.
We and other life on Earth need Oxygen, but too much Oxygen is bad, everything goes on fire.