Submitted by WeedCat1 t3_zr40m7 in askscience
So if there is oxygen present, then the pyruvate would go to the mitochondria and do aerobic cellular respiration. If there is no oxygen it would instead do fermentation from what I understand. But I am curious about what biochemically causes this change aside from just the lack of oxygen. Like if there's some transport protein that is deactivated or something when there's no oxygen somehow that then causes it to not be moved into the mitochondria.
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Yeah. But why?
Substrates flow down their concentration gradients the same way that if you pour concentrated syrup into water, it will naturally spread all throughout. The reason why it does this is that it is thermodynamically favorable to equilibrate like this.
This makes sense but my question is that the molecules outside the mitochondria don't "know" that the concentration within the matrix is lower. Is it that the receptor is sensitive to concentration of pyruvate within the matrix, so that its activity depends on the intra-mitochondrial concentration?
Thinking out loud here but could it be that the affinity of the receptor depends on the extra-mitochondrial matrix regardless of within? Maybe affinity is the wrong word too, more like the increased probability of pyruvate binding to the receptor the higher the concentration.
Nothing has to know about the concentration gradient. As long as there is a way to flow, substrates will spontaneously flow.
Exactly. Like water flows downhill. Or a fart finds it’s way into your nose.
>“This makes sense but my question is that the molecules outside the mitochondria don't "know" that the concentration within the matrix is lower.”
They don’t need to “know”. They are randomly bouncing around, if there are more bouncing around on one side of a wall odds are more will pass through the gate to the side with less bouncing around than the other way around. And so they flow with the concentration gradient.
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Probably there are some other mechanisms involved, but one regulation is the depletion of free NAD+. If you don’t have any oxigen to finally receive the electrons made on glicolisis - Krebs cycle, all NAD+ gets converted to NADH, and the reactions that requiere free NAD+ just stop. To avoid all these things, you can convert piruvate to lactic acid (lactic fermentation). This reaction uses one NADH, and converts it to NAD+ again, so that the glicolisis - lactic fermentation can continue. This reaction takes place in the cell cytoplasm, not on the mitochondria, separating in from other processes.
I love this..so much depends on there being enough oxygen to accept electrons at the end of the electron transport chain. If reaction intermediates build up, you can be sure pyruvate will also build up and preferentially undergo fermentation.
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Obviously it’s way more complex than this, but even with oxygen, if the glycolysis rate is high, not all pyruvate gets into the mitochondria. U/metacelcus explains it better, but a simpler explanation I use is to think of it like a sink faucet that’s turned up so high that the drain can’t drain it fast, and some water overflows the basin. In this case, glucose to pyruvate is the faucet, the drain is the mitochondria and the overflow is the formation of lactate. It’s not a perfect analogy, but does reasonably well to get the concept across in undergrad exercise physiology classes.
I don’t think we fully know the answer to this question though it is a very good one. In some tissues, even in the presence of oxygen, pyruvate doesn’t go to the mitochondria. For example, the eye is one of the most metabolically active tissues in the body. Oxygen is present but ~95% of pyruvate is converted to lactate and ~5% enters the mitochondria. Pyruvate transporters on mitochondria are present, just rarely used.
I think it’s highly dependent upon the concentration and regulation of lactate dehydrogenase (LDH) which converts pyruvate to lactate. If LDH activity is high, transformation of pyruvate to lactate happens more quickly than transport of pyruvate into the mitochondria. NAD:NADH ratio definitely plays a large role in regulating this.
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We have the HIF-pathway to measure the oxygen level in the cell. If oxygen levels are too low, aerobic dissimilation is suppressed (and modified). (a bit controversial but as far as I understand:) the anaerobic reaction/dissimilation always happens. It occurs near the cell wall. At the mitochondria (between the double walls) lactate is reverted back to pyruvate and the pyruvate can enter the mitochondria inner lumen for aerobic dissimilation. The HIF-pathway can (indirectly) suppress and modify this process. If lactate is no longer used by the mitochondria the concentration of lactate in the cell increases and the lactate flow out of the cell increases.
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-Metacelsus- t1_j11tl4y wrote
This paper is a good review of pyruvate transport into the mitochondria. Basically, pyruvate can flow across the mitochondrial outer membrane using non-selective anion channels such as VDAC1. There are two proteins, MPC1 and MPC2 (named for being mitochondrial pyruvate carriers), that form a complex that transports pyruvate through the inner membrane into the mitochondrial matrix, where the oxidation happens. The MPC complex carries a proton along with pyruvate (which is known as proton symport). Since pyruvate is negatively charged this means the overall transport process is charge-neutral across the inner membrane.
In general, compounds diffuse from regions of high concentration to regions of low concentration. Since pyruvate is consumed in the mitochondrial matrix, the concentration will be lower there, so pyruvate will diffuse inside if the proper transport proteins are present. In absence of oxygen, pyruvate won't be oxidized in the mitochondrial matrix, so this concentration gradient would be much lower (or absent entirely).