Biochem FA clarification

[NYMed]

So I noticed that one of the FA corrections says that the rate-limiting step of gluconeogenesis is fructose 1,6 bisphosphate and not pyruvate carboxylase. I was just going through questions on USMLERx, and one of the question directly asked me what the rate limiting step was. I put down fructose 1,6 bisphosphate, but the correct answer was pyruvate carboxylase. I looked it up in Lippincott's Biochem and BRS biochem, and neither one mentions which is the rate-limiting step, although both list pyruvate carboxylase as the first step. Can somebody clarify this for me? Do you think USMLERx has pyruvate carboxylase as the answer because that's what it says in FA and it's made by the same people? Or is that actually the answer? Thanks!

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[alpha06]

So I noticed that one of the FA corrections says that the rate-limiting step of gluconeogenesis is fructose 1,6 bisphosphate and not pyruvate carboxylase. I was just going through questions on USMLERx, and one of the question directly asked me what the rate limiting step was. I put down fructose 1,6 bisphosphate, but the correct answer was pyruvate carboxylase. I looked it up in Lippincott's Biochem and BRS biochem, and neither one mentions which is the rate-limiting step, although both list pyruvate carboxylase as the first step. Can somebody clarify this for me? Do you think USMLERx has pyruvate carboxylase as the answer because that's what it says in FA and it's made by the same people? Or is that actually the answer? Thanks!

Yes. USMLERx and FA are both wrong. The rate-limiting enzyme for gluconeogenesis is fructose-1,6-bisphosphatase.

My source: RR biochem 2nd ed. by pelley and goljan. p.95

 

[agranulocytosis]

My Kaplan Biochem text technically doesn't state that fructose-1,6-bisphosphatase is the rate-limiting enzyme like it does for other processes. BUT, for all intents and purposes, this is the enzyme that's most regulated and thus serves the function of a rate-limiting enzyme (i.e. activation by ATP and inhibition by AMP and fructose-2,6-bisphosphate).

"f-1,6-bpase in the cytoplasm is a key control point of gluconeogenesis" as quoted from Kaplan.

 

[DwyaneWade]

Yes. USMLERx and FA are both wrong. The rate-limiting enzyme for gluconeogenesis is fructose-1,6-bisphosphatase.

My source: RR biochem 2nd ed. by pelley and goljan. p.95

Yes, I got a similar question wrong OP and looked it up in the big ol' biochem text. It's F6BP

 

[hdu]

Allow me some observations with my best intention:

NYMed: "So I noticed that one of the FA corrections says that the rate-limiting step of gluconeogenesis is fructose 1,6 bisphosphate and not pyruvate carboxylase"

DwyaneWade "Yes, I got a similar question wrong OP and looked it up in the big ol' biochem text. It's F6BP"

Comments:

fructose 1,6 bisphosphate is a metabolite. It can not be the rate limiting step. You can say "the formation of Fructose 1,6 bisposphate is the rate limiting step" or "the degradation of Fructose 1,6 bisphosphate is the rate limiting step..." but not the metabolite per se. The name of the enzyme is fructose 1,6 bisphosphatase.

F6BP is not this metabolite name. F1,6BP is. If you say F6BP you are saying Fructose 6 Bisphosphate. It would mean a fructose with two phosphates in position 6.
F2,6BP is a different metabolite that is very important in the regulation of gluconeogenesis and glycolysis. Be aware of the differences and be specific about the metabolite name and the position of the two phosphates in fructose.

Do not hesitate to contact me if you think I can be of some help

My blog www.biochemistryquestions.wordpress.com
.

 

[DwyaneWade]

Allow me some observations with my best intention:

NYMed: "So I noticed that one of the FA corrections says that the rate-limiting step of gluconeogenesis is fructose 1,6 bisphosphate and not pyruvate carboxylase"

DwyaneWade "Yes, I got a similar question wrong OP and looked it up in the big ol' biochem text. It's F6BP"

Comments:

fructose 1,6 bisphosphate is a metabolite. It can not be the rate limiting step. You can say "the formation of Fructose 1,6 bisposphate is the rate limiting step" or "the degradation of Fructose 1,6 bisphosphate is the rate limiting step..." but not the metabolite per se. The name of the enzyme is fructose 1,6 bisphosphatase.

F6BP is not this metabolite name. F1,6BP is. If you say F6BP you are saying Fructose 6 Bisphosphate. It would mean a fructose with two phosphates in position 6.
F2,6BP is a different metabolite that is very important in the regulation of gluconeogenesis and glycolysis. Be aware of the differences and be specific about the metabolite name and the position of the two phosphates in fructose.

Do not hesitate to contact me if you think I can be of some help

My blog www.biochemistryquestions.wordpress.com
.

I know the difference

Sue me for abbreviating fructose 1 6 bisphosphatase as F6BP. Dropped a 1.

Thanks for the offer though!

 

[osli]

Nevermind

 

[NYMed]

Allow me some observations with my best intention:

NYMed: "So I noticed that one of the FA corrections says that the rate-limiting step of gluconeogenesis is fructose 1,6 bisphosphate and not pyruvate carboxylase"

DwyaneWade "Yes, I got a similar question wrong OP and looked it up in the big ol' biochem text. It's F6BP"

Comments:

fructose 1,6 bisphosphate is a metabolite. It can not be the rate limiting step. You can say "the formation of Fructose 1,6 bisposphate is the rate limiting step" or "the degradation of Fructose 1,6 bisphosphate is the rate limiting step..." but not the metabolite per se. The name of the enzyme is fructose 1,6 bisphosphatase.

F6BP is not this metabolite name. F1,6BP is. If you say F6BP you are saying Fructose 6 Bisphosphate. It would mean a fructose with two phosphates in position 6.
F2,6BP is a different metabolite that is very important in the regulation of gluconeogenesis and glycolysis. Be aware of the differences and be specific about the metabolite name and the position of the two phosphates in fructose.

Do not hesitate to contact me if you think I can be of some help

My blog www.biochemistryquestions.wordpress.com
.

Sorry, I meant to say fructose 1,6 bisphosphatase

 

[LUBDUBB]

F16BPase is the rate-limiting step in gng. However, the question does bring up an important concept though, which is: Pyruvate handling in fasting(GNG) vs. Fed state (krebs cycle, Fatty acid synthesis).

In Fed state, glycolysis -> pyruvate --> acetyl CoA - VIA PDH

In the fasting state, when you need gluconeogensis, PDH is inhibited (and Pyruvate Carboxylase is turned on) by acetylCoa/NADH from B-oxid of FA;this is to ensure that PYR (made from substrates) is shunted to OAA to make glucose and not futilely cycled through krebs.

Another major major regulatory point, I believe, is PEPCK, whose gene transcription is induced by Glucagon.