RBC & Anaerobic Glycolysis

[SaintJude]

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Since red blood cells solely derive their ATP solely from anaerobic glycolysis, how do they regenerate their NAD+ ? I don't think it's fermenation, because I just read that fermentation only occurs in an anerobic cell forced to revert to anaebolic metabolism.

 

[chiddler]

there aren't any other ways that they can do it.

from wiki:

"As a result of not containing mitochondria, these cells use none of the oxygen they transport; instead they produce the energy carrier ATP by the glycolysis of glucose and lactic acid fermentation on the resulting pyruvate."

 

[SaintJude]

Is that statement saying that they also produce ATP via lactic acid fermentation? Because that's definitely wrong. Or is saying that they regenerate NAD+ via lactic acid fermentation?

 

[chiddler]

Is that statement saying that they also produce ATP via lactic acid fermentation? Because that's definitely wrong. Or is saying that they regenerate NAD+ via lactic acid fermentation?

They are saying both. ATP is produced via lactic acid fermentation and NAD is regenerated by reducing the pyruvate to lactic acid.

 

[SaintJude]

Ok, so its then that ATP is produced via glycolysis (only-biochem sources say only via glycolysis) and NAD+ is regenerated via fermentation.

 

[chiddler]

Ok, so its then that ATP is produced via glycolysis (only-biochem sources say only via glycolysis) and NAD+ is regenerated via fermentation.

Please understand that lactic acid is a type of fermentation that includes glycolysis.

ATP is produced via lactic acid fermentation. This means that glycolysis breaks glucose down into pyruvate and is then processed into lactic acid. NAD is also regenerated from NADH from this fermentation process just as energy, ATP, is made.

 

[SaintJude]

Oh, I see (finally...) Fermentation is part of glycolysis. Thanks.

 

[MedPR]

Can someone show/explain to me why/how NAD+ is regenerated (from NADH?) from fermentation. I guess it's evident now that I do not know wha the role of NADH/FADH2/NADPH/etc are. If you show them to me in a reaction, I can tell you if they are reduced or oxidized, but otherwise I know nothing about them.

 

[chiddler]

yup it's a really simple reaction

and i'm sure you can imagine how it differs slightly for ethanol production. understand or need explanation?

 

[gravitywave]

Please understand that lactic acid is a type of fermentation that includes glycolysis.

ATP is produced via lactic acid fermentation. This means that glycolysis breaks glucose down into pyruvate and is then processed into lactic acid. NAD is also regenerated from NADH from this fermentation process just as energy, ATP, is made.

ATP is not produced via lactic acid fermentation. not in RBCs anyway. the RBCs must have some way of regenerating NAD+ because of the action of glyceraldehyde 3-phosphate dehydrogenase on G3P in glycolysis. otherwise all their NAD+ gets turned into NADH and glycolysis would grind to a halt. in most cells, NADH gets sent back to NAD+ as part of oxidative phosphorylation in the Krebs cycle. but not in RBCs: they have no mitochondria and hence no OxPhos! so instead, the RBCs get rid of their pyruvate via lactate dehydrogenase. this gets NADH back to NAD+ as shown in the mechanism above, and glycolysis can continue.

the lactate goes back to the liver, which uses it as substrate for gluconeogenesis.

Oh, I see (finally...) Fermentation is part of glycolysis. Thanks.

no. it is not. glycolysis is the process of generating ATP from glucose via substrate phosphorylation, with pyruvate as the final product. pyruvate can then go down any number of pathways, of which fermentation is one.

 

[MT Headed]

http://en.wikipedia.org/wiki/Fermentation_(biochemistry)

"Fermentation is the process of extracting energy from the oxidation of organic compounds, such as carbohydrates, ..."

"Sugars are the most common substrate of fermentation, and typical examples of fermentation products are ethanol, lactic acid, ..."


I got this wrong on a biology lab quiz once; it's the sort of thing I remember to this day. It's a trivial piece of knowledge, but if you are communicating with another biologist the word fermentation refers to the complete path from sugar to lactic acid or ethanol or whatever.

 

[MedPR]

ATP is not produced via lactic acid fermentation. not in RBCs anyway. the RBCs must have some way of regenerating NAD+ because of the action of glyceraldehyde 3-phosphate dehydrogenase on G3P in glycolysis. otherwise all their NAD+ gets turned into NADH and glycolysis would grind to a halt. in most cells, NADH gets sent back to NAD+ as part of oxidative phosphorylation in the Krebs cycle. but not in RBCs: they have no mitochondria and hence no OxPhos! so instead, the RBCs get rid of their pyruvate via lactate dehydrogenase. this gets NADH back to NAD+ as shown in the mechanism above, and glycolysis can continue.

the lactate goes back to the liver, which uses it as substrate for gluconeogenesis.



no. it is not. glycolysis is the process of generating ATP from glucose via substrate phosphorylation, with pyruvate as the final product. pyruvate can then go down any number of pathways, of which fermentation is one.

So there is lactate dehydrogenase in RBCs? RBCs do glycolysis, converting 1 glucose to 2 pyruvate and 2 NADH, then lactate dehydrogenase converts 2 pyruvate and 2 NADH into NAD+ and lactate. Then the lactate diffuses out of the RBC?

 

[chiddler]

ATP is not produced via lactic acid fermentation. not in RBCs anyway. the RBCs must have some way of regenerating NAD+ because of the action of glyceraldehyde 3-phosphate dehydrogenase on G3P in glycolysis. otherwise all their NAD+ gets turned into NADH and glycolysis would grind to a halt. in most cells, NADH gets sent back to NAD+ as part of oxidative phosphorylation in the Krebs cycle. but not in RBCs: they have no mitochondria and hence no OxPhos! so instead, the RBCs get rid of their pyruvate via lactate dehydrogenase. this gets NADH back to NAD+ as shown in the mechanism above, and glycolysis can continue.

the lactate goes back to the liver, which uses it as substrate for gluconeogenesis.



no. it is not. glycolysis is the process of generating ATP from glucose via substrate phosphorylation, with pyruvate as the final product. pyruvate can then go down any number of pathways, of which fermentation is one.

I've read and reread this a few times and i'm not sure I understand. First you're saying that ATP is not produced via lactic acid fermentation. Next, you are saying that they get rid of NADH via lactate dehydrogenase. But this is the enzyme that is responsible for the last part of lactate fermentation.

What am I missing?

 

[gravitywave]

So there is lactate dehydrogenase in RBCs? RBCs do glycolysis, converting 1 glucose to 2 pyruvate and 2 NADH, then lactate dehydrogenase converts 2 pyruvate and 2 NADH into NAD+ and lactate. Then the lactate diffuses out of the RBC?

yes

I've read and reread this a few times and i'm not sure I understand. First you're saying that ATP is not produced via lactic acid fermentation. Next, you are saying that they get rid of NADH via lactate dehydrogenase. But this is the enzyme that is responsible for the last part of lactate fermentation.

What am I missing?

perhaps MT Headed is correct when it comes to terminology, i don't know about that. i look at the pathways from branchpoint to branchpoint. if you are talking about "lactic acid fermentation" as glucose -> pyruvate -> lactate (the whole package), then sure you are making ATP. that's what glycolysis is all about. i just have never heard anyone refer to anything past pyruvate as being part of glycolysis, as someone did. glycolysis as part of fermentation, sure, i could see that. fermentation as part of glycolysis, nope.

glycolysis makes ATP from glucose. the byproducts are NADH from NAD+, and pyruvate. in order for RBCs to continue glycolysis and stay alive, they must regenerate NAD+; they have no use for NADH. lactate dehydrogenase is the last step that they must take to get the NAD+ back. the result is lactate, which they excrete.

 

[chiddler]

yes



perhaps MT Headed is correct when it comes to terminology, i don't know about that. i look at the pathways from branchpoint to branchpoint. if you are talking about "lactic acid fermentation" as glucose -> pyruvate -> lactate (the whole package), then sure you are making ATP. that's what glycolysis is all about. i just have never heard anyone refer to anything past pyruvate as being part of glycolysis, as someone did. glycolysis as part of fermentation, sure, i could see that. fermentation as part of glycolysis, nope.

glycolysis makes ATP from glucose. the byproducts are NADH from NAD+, and pyruvate. in order for RBCs to continue glycolysis and stay alive, they must regenerate NAD+; they have no use for NADH. lactate dehydrogenase is the last step that they must take to get the NAD+ back. the result is lactate, which they excrete.

well i'm happy. i was ready to cry if you told me i was wrong because this is pretty foundational stuff lol

 

[gravitywave]

well i'm happy. i was ready to cry if you told me i was wrong because this is pretty foundational stuff lol

sorry for any confusion. reading back now over the posts, i see what happened.

 

[SaintJude]

regardless, thank you gravitywave! your input was really crucial and this topic makes sense now. very inspiring that you know all this stuff & you're in med school. thanks