Lactic Acid

[DingDongD]

I am kind of confused as what mechanism that results in lactic acidosis?

In glycolysis, the carboxyl group never does have a hydrogen. I understand the reasoning behind this, since the cytosol is pretty neutral.

But, what I do not understand is it not due to glycolysis that results in lactic acidosis? Why is it linked to lactate? It seems that there would not be any presence of lactic acid to begin with.

If you would be kind to explain my misunderstanding, I would be grateful. Thank you.

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[theonlytycrane]

once tissues have reached anaerobic conditions, lactate starts to build up. CO2 and H2O may be present as well from the anaerobic pathway (previously) to generate ATP. CO2 and H2O may form H2CO3 which weakly dissociates to protonate lactate and just generally lower the pH of tissues overall.

 

[aldol16]

But, what I do not understand is it not due to glycolysis that results in lactic acidosis? Why is it linked to lactate? It seems that there would not be any presence of lactic acid to begin with.

Glycolysis does not produce lactate. Lactate is produced only under anaerobic conditions or in cells that lack a mitochondria to carry out oxidative phosphorylation. The reason lactate is produced under anaerobic conditions is because in glycolysis, the GAPDH reaction requires NAD+. So after each cycle, you need to regenerate NAD+ from NADH - otherwise, the pathway stops. Under aerobic conditions, this is not a problem because the TCA cycle generates 3 NADH per turn. But under anaerobic conditions, that doesn't happen since oxidative phosphorylation can't occur and NADH builds up. So instead, pyruvate is converted to lactate. Do your formal charges and you'll see that this is a reduction, meaning that NADH is oxidized back to NAD+ so that glycolysis can continue. So lactate begins to build up. This occurs in your muscles during vigorous exercise and it's why humans cannot sustain a sprint for very long.

The lactate then enters the Cori cycle and is "redeemed" for glucose from the liver. Fun fact: this is basically fermentation and bacteria face the same problem - they solve it by converting pyruvate to acetaldehyde and then ethanol. This also regenerates NADH and gives us our favorite beverages.

once tissues have reached anaerobic conditions, lactate starts to build up. CO2 and H2O may be present as well from the anaerobic pathway (previously) to generate ATP. CO2 and H2O may form H2CO3 which weakly dissociates to protonate lactate and just generally lower the pH of tissues overall.

This is not possible. Carbonic acid has a pKa of 6 while lactic acid has a pKa of around 4. So carbonic acid will never donate a proton to lactate. Under physiological conditions, both would exist predominantly in the deprotonated form.

 

[theonlytycrane]

Glycolysis does not produce lactate. Lactate is produced only under anaerobic conditions or in cells that lack a mitochondria to carry out oxidative phosphorylation. The reason lactate is produced under anaerobic conditions is because in glycolysis, the GAPDH reaction requires NAD+. So after each cycle, you need to regenerate NAD+ from NADH - otherwise, the pathway stops. Under aerobic conditions, this is not a problem because the TCA cycle generates 3 NADH per turn. But under anaerobic conditions, that doesn't happen since oxidative phosphorylation can't occur and NADH builds up. So instead, pyruvate is converted to lactate. Do your formal charges and you'll see that this is a reduction, meaning that NADH is oxidized back to NAD+ so that glycolysis can continue. So lactate begins to build up. This occurs in your muscles during vigorous exercise and it's why humans cannot sustain a sprint for very long.

The lactate then enters the Cori cycle and is "redeemed" for glucose from the liver. Fun fact: this is basically fermentation and bacteria face the same problem - they solve it by converting pyruvate to acetaldehyde and then ethanol. This also regenerates NADH and gives us our favorite beverages.



This is not possible. Carbonic acid has a pKa of 6 while lactic acid has a pKa of around 4. So carbonic acid will never donate a proton to lactate. Under physiological conditions, both would exist predominantly in the deprotonated form.

Thanks for the clarification! Clear and helpful post

 

[NextStepTutor_2]

Thanks for the clarification! Clear and helpful post

This concept is a great illustration of HOW the MCAT tests this dry biochem material. lactic acid and cause discomfort, and throw off the pH of the body is left unchecked (though it would take a lot of it). The only reason our body does it is because cells MUST regenerate the NAD+ needed to continue glycolysis when the body is low on oxygen (e.g. anaerobic conditions).

This is the kind of understanding the MCAT will want from you. Not jus the WHAT, but the WHY.

Good luck!

 

[DingDongD]

Hi, thank you for the answer. I understand why lactate is necessary from your explanation. However, I do not understand the acid/base mechanism that results in low pH from lactate, and why does it produce lactic acidosis. That's my main problem. I do not think I wrote my question properly.

 

[aldol16]

This will be of interest to you: http://www.ncbi.nlm.nih.gov/pubmed/15308499