UW - RBC glycolysis

[osli]

Can someone help me understand this one?

To paraphrase the question: 'Some cells can't net ATP through glycolysis. They expend energy in a reaction catalyzed by phosphoglycerate kinase rather than producing ATP with the energy. Which cells are most likely to use the path described above?'

Erythrocytes

Now, the other choices didn't make much sense either, but can someone explain this to me? I certainly thought that phosphoglycerate kinase was the step producing ATP, and that by bypassing it you didn't. Isn't the alternative energy expending path in RBC's catalyzed by phosphoglycerate mutase?

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[pistachio]

From 1,3-BPG, you can either make 3-phosphoglycerate and 1 ATP using phopshoglycerate kinase, or you can use a mutase to make 2,3-BPG, which the RBCs need to control their Hb. From 2,3-BPG to 3-phosphoglycerate, the enzyme is a phosphatase which produces no ATP. So RBCs, in making 2,3-BPG, lose that ATP. Since that step is done twice in normal glycolysis (2 molecules of 1,3-BPG fom 1 glucose), and 2 ATP are invested in glycolysis, the RBCs net no ATP from that reaction.

 

[pistachio]

Oh...I see what you're saying. Maybe the RBCs start from 3-phosphoglycerate, use ATP to make 1,3-BPG, and then the mutase to make 2,3-BPG?

Otherwise, I have no idea...

 

[osli]

I'm assuming that since RBC's utilize glucose, everything flows from the top down. I can't see how the question/answer can make any sense unless it was a typo/error in the question, and kinase should have been mutase. Unless I really just don't understand what they're getting at. Since nearly 50% got this question correct, I want to make sure there isn't a gap in my understanding and that I'm not missing something obvious.

Anyone else?

 

[DolphinSwim]

The way I understood that question was that 1, 3 BPG has 2 routes it can take in the RBC
1. converted to 3PG by phosphoglycerate kinase (generates 1 ATP)
2. converted to 2BPG by phosphoglycerate mutase ( enzyme abundant in RBCs and not other tissues listed in the question)...this is upregulated by hypoxia but does NOT generate ATP

Option 1 is part of the normal glycolytic pathway
Option 2 is is like a detour to produce 2,3 BPG---> which enters back into glycolysis by being converted back to 3PG by a phosphatase

Just what I interpreted from the question....hope its helpful!

 

[osli]

Oh... so they were saying that this cell expends energy in a reaction usually catalyzed by phosphoglycerate kinase that produce ATP in other cells, but not catalyzed by that enzyme when this cell uses the alternative non-ATP producing pathway.

Well, if they would have just said that...

BTW, I went back and looked at the question, and the wording is almost identical to what I wrote above. It really is that poorly written.

 

[DolphinSwim]

The way I understand it is that its more of secondary simultaneous pathway which is upregulated or downregulated based on hypoxia...therefore most of the 1,3 BPG goes through the traditional pathway while some gets siphoned off to form 2,3 BPG. RR Path lists it as the Luebering-Rapaport Pathway. Anyway, UW should revise that one.....it pretty confusing!!! Good luck!

 

[osli]

Must have been a COMLEX question writer responsible for that one.

 

[RxnMan]

Yesterday I had a question about a patient with respiratory distress who takes ziluton and something called "salsalate". Had to guess the condition.

I guessed asthma exacerbation (via ziluton).

Turned out it was a partially compensated combined metabolic acidosis / resp alkalosis. Evidently salsalate = ASA. The combination makes sense, but the misspelling...

 

[osli]

Seeing "salsalate" I'd have probably started looking for GERD or something similar in the answer choices!

 

[indo]

I prefer mango salsalate. mmm.



2,3-bpg synthesis skips the ATP yielding reaction of glycolysis.

 

[osli]

Yeah, I get that, it just isn't how they worded the question. Very poorly written.

 

[indo]

Oh, well yeah. If med school involved understandable questions we'd all get perfect grades.

 

[osli]

True that. I remember one particularly good physiology question covering muscle prestretch/passive tension/active tension etc. It started something like "you're about to pick up a mug of coffee..." and left you guessing as to whether that meant you were just contemplating picking it up, or had actually grabbed it and taken up all the slack in your muscle and were just about to get it to lift off the table...

 

[Its_MurDAH]

Yesterday I had a question about a patient with respiratory distress who takes ziluton and something called "salsalate". Had to guess the condition.

I guessed asthma exacerbation (via ziluton).

Turned out it was a partially compensated combined metabolic acidosis / resp alkalosis. Evidently salsalate = ASA. The combination makes sense, but the misspelling...

It's funny I remember a question just like that in kaplan qbank and I was pissed that they missspelled it.
That was until I came across this:
http://0-www.nlm.nih.gov.catalog.llu.edu/medlineplus/druginfo/medmaster/a682880.html

Apparently, a drug called salsalate does exist and it is, in fact, an nsaid.

 

[DrFraud]

Oh... so they were saying that this cell expends energy in a reaction usually catalyzed by phosphoglycerate kinase that produce ATP in other cells, but not catalyzed by that enzyme when this cell uses the alternative non-ATP producing pathway.

Well, if they would have just said that...

BTW, I went back and looked at the question, and the wording is almost identical to what I wrote above. It really is that poorly written.

Yeah, I had a problem with this one too. I checked with someone who had a grad degree in biochem. I also looked it up just in case I was having a brain hickup, but I still think the stem has a flaw:

"They expend energy in a reaction catalyzed by phosphoglycerate kinase rather than producing ATP with the energy..."

and i thought, after reading the explaination, it should read:

"They expend energy in a reaction catalyzed by phosphoglycerate mutase rather than producing ATP with the energy..."

I even went so far as to write UW, but I did not get a response. So after I had this question, I stopped taking everything that I read in UW as dogma, and I double checked when ever I read something like this that didn't make any sense and I didn't second guess myself.

There still might be something I don't understand, so if anyone can also clarify this further for me, please let me know.

 

[hdu]

Glycolysis is the same in RBC until the formation of 1,3 bisphosphoglycerate. Once it is formed, it can follow two ways (there is a bisphosphoglyceromutase in RBC that allows other reaction)


2,3 bis (P) glycerate-<--1,3 bis (P) glycerate--> 3 (P) glycerate + ATP
_________________MUTASE___________________KINASE________________


In Red Blood Cells, only 75 to 85 % of the glucose follows the classic glycolytic pathway, through the glyceroKINASE reaction (3 (P) glycerate-> 2 (P) glycerate, etc)

In this classic way, as you know, two net ATP of anaerobic glycolysis are produced:

Glucose to glucose 6 (P)______________________________-1 ATP
Fructose 6 (P) to Fructose 1, 6 di (P)____________________- 1 ATP
1,3 bis (P) glycerate --> 3 (P) glycerate x2)______________+ 2 ATP
(P) enol pyruvate to Pyruvate (x2)______________________ + 2 ATP
-----------
NET______________________________________________ + 2 ATP

The other 25 to 15 % of glucose is converted, in a reaction catalyzed by Bis phosphoglycerateMUTASE, to 2,3 bis (P) glycerate, a compound necessary for the regulation of the affinity of hemoglobin for Oxygen.

The ulterior degradation of 2,3 bis(P) glycerate is

2,3 bis (P) glycerate -> 3 (P) glycerate + (P) , (catalyzed by a Phosphatase, so, there is not gain of ATP like in the glycolytic reaction of 1,3 bis (P) glycerate to 3 phosphoglycerate by the phosphogycerate kinase)

The energetic balance using this way, that is called the Bisphosphoglycerate (BPG) shunt, is:

Glucose to glucose 6 (P)_______________________________ -1 ATP
Fructose 6 (P) to Fructose 1, 6 di (P)_____________________- 1 ATP
(P) enol pyruvate to Pyruvate (x2)_______________________+ 2 ATP
-------------
NET ________________________________________________ 0 ATP

So, in the Red Blood Cells, a certain quantity of glucose follows the classic glycolytic pathsway to produce energy for the red blood cell, while some molecules follow the bisglycerophosphate shunt to produce 2,3 bisphosphoglycerate, necessary for the regulation of the binding of Oxygen to Hemoglobin.

I hope it helps.

(My blog: www.biochemistryquestions.wordpress.com)

 

[osli]

Yeah, that helps solidify things again for me, but it doesn't help the error in the UWorld question stem.