Talk:Gluconeogenesis

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Disputed Image

I'm no specialist, so have not edited. Cannot gluconeogenesis also be caused by excess and/or too rapid protein intake? MIchael 07:56, 24 July 2006 (UTC) Douglas Michael Massing

The diagram "showing" gluconeogenesis is actually of glycolysis. This is a significant error and needs to be changed. Here is a very brief illustration that provides a better overview of gluconeogenesis.

--Dbrouse 00:02, 17 August 2006 (UTC)

The above illustration is a terrible instance of gluconeogenesis. The only problem with the diagram in the main article is its lack of distinction with glycolysis, which could be facilitated by the addition of enzymes.

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By "terrible" - I am assuming that you are meaning that the illustration I provided as an idea is missing the detailed steps of metabolism. Note that I never proposed it was appropriate for the article page. If my interpretation of your meaning of "terrible" is wrong, please reply what it is about the illustration that is terrible. The illustration I submitted to this discussion page was created to show that the concept of gluconeogenesis really is NOT just a reversal of glycolysis. Glycoylsis is the metabolic pathway that converts 1 glucose into 2 pyruvates. Gluconeogensis represents the pathways that allow for new glucose to be made from glycerol, and some amino acids. Gluconeogenesis does utilize a pathway that can be thought of as a reversal of glycolysis but it is MORE than that.

My experience has been that biochemists have a tendency to think of gluconeogenesis as a reversal of glycolysis -- with a few modifications. (Berg,Tymoczko, & Stryer, Biochemistry, fifth Ed - online via Entrez Bookshelf) But physiologists, and others who study metabolism at the systemic and organism levels have a broader view of gluconeogensis. (Guyton & Hall, Textbook of Medical Physiology, 9th Ed.)They have a tendency to ALSO include the triglyceride mobilization from adipocytes and utilization of amino acids as part of overall process of gluconeogenesis. This is probably because at the organ/system/organism levels of organization it is important to understand how the different tissues and organs are regulated to provide the raw materials to make the new glucose.

Anyway, I notice that the diagram that initiated this discussion has been removed from the article page. If someone has an appropriate diagram that includes the broader view of gluconeogenesis, it would be great to have something to look at. I think that the broader view, that I have attempted to describe, should be used as it better represents dictionary definitions of gluconeongenesis (I looked at several including Tabers 20th ed.) and it INCLUDES the narrower veiw (reversal of glycolysis with modifications) of gluconeogenesis that is used by some groups of people. I could always request that my students help me make a new diagram for Wikipedia when we study metabolism next term... I hope it doesn't come to that because I have been known to make terrible illustrations. :-) Dbrouse

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The diagram in the main article does illustrate a very vague gluconeogenesis route. No enzymes are shown. However, the Gluconeogenesis pathway is similar to the reverse of Glycolysis except for the use of four different enzymes (Pyruvate carboxylase, Phosphoenolpyruvate carboxykinase, Fructose-1,6 bisphosphatase, and Glucose-6 phosphatase) which is why they look similar. You can see the Gluconeogenesis route on the right of the pathway but a better diagram should be used to see the enzymes used.

-AndyKarlesky

Dispute

The accuracy of this article is disputed as the diagram shows glycolysis and not gluconeogenesis. The reverse reactions of glycolysis (shown in the image) can cause "new" glucose to be formed from small metabolites but there is more to gluconeogensis than just a reverse of glycolysis. Glycerol, from lipids, and deaminated amino acids are the major raw materials for forming new glucose.—Preceding unsigned comment added by Dbrouse (talk • contribs) Moved from article --Wafulz 05:38, 22 October 2006 (UTC)

i concur

- Mike Brubaker, Whitman College

The problem also exists for the section titled Pathway. It begins with pyruvate, but doesn't outline how substances such as lactic acid are converted to pyruvate to begin with. perhaps the problem is that different substances (amino acids, fatty acids, glycerol, etc.) are metabolized differently? Lactic acid, for example, is converted to pyruvate by the Cori cycle. Perhaps if only a few pathways exist to convert different classes of substances to pyruvate, these could all be described seratley, or a wikilink could be provided to an article describing each pathway? Theonly pathway currently mentioned in the article is the Cori cycle, which metabolizes lactic acid.

AhsenM (talk) 01:19, 8 September 2009 (UTC)

The illustration on the page now doesn't create glucose; it's a similar molecule but it is missing a carbon (C6).

When gluconeogenesis occurs.

The article implies that gluconeogenesis only occurs during starvation or intense excercize. This is quite misleading. Gluconeogenesis is an ongoing process in the body and not isolated to specific stresses. It is essential to reuse the lactate that accumulates during excercize back into pyruvate and then into glucose. It is also the major route for glycerol metabolism. It is an important biological pathway for many other purposes.

No futile cycle?

In the statement concerning the existence of a futile cycle, the article implies that glycolysis and gluconeogenesis are independent processes. This is an unfortunate conceptual error in understanding of the regulatory mechanisms of the two pathways. Both processes DO occur at the same time; thus, a futile cycle is continually in effect to a certain degree. The key is that one pathway is upregulated while the other is inhibited depending upon the given physiological state (ie. the presence of glucagon, insulin, epinephrine, etc). The cellular benefit gained from allowing the seemingly wasteful futile cycle is that it allows a very rapid response by hepatocytes (kidney cortex, too) to systemic change in serum glucose levels...a very good thing indeed if one is being chased by an angry lion!

If there are no disputes, I will come back and make the corrections with appropriate citation.

Awbacon 05:12, 8 September 2007 (UTC)

In my reading of it, it doesn't seem to imply separate cycles. A futile cycle, however, would be when both pathways are operating at their full ability (thus negating each other physiologically). While both are continuously running, the inhibition of each cycle on the other through the three regulatory enzymes prevents it from becoming actually "futile". Schu1321 (talk) 07:41, 12 May 2008 (UTC)

You mention some very relevant information. Perhaps add a section on the usefullness of gluconeogenesis, and another on the physiological states that inhibit or promote it? The clarification about the futile cycle would probably bes tfit into the section on usefullness. AhsenM (talk) 01:17, 8 September 2009 (UTC)

WikiProject class rating

This article was automatically assessed because at least one WikiProject had rated the article as start, and the rating on other projects was brought up to start class. BetacommandBot 16:27, 10 November 2007 (UTC)

New image, editing

I added a new image I made for the article and also reworked a large amount of the article text. I have the original image and can make changes easily, so if you notice any errors feel free to let me know and I can upload a revision. Schu1321 (talk) 07:43, 12 May 2008 (UTC)

I do not know how to make a new topic, but glucose is drawn incorrectly in the gluconeogenesis pathway diagram. The sugar that is labeled as glucose is a pentose, not a hexose, so it cannot be glucose. The 6th carbon needs to be drawn coming from C5 (the carbon to the left of the O in the ring). The hydroxyl group that is currently attached to C5 should be attached to C6.173.197.152.66 (talk) 18:07, 29 October 2013 (UTC)

Overview

Hey, just remembering that we need an overview in this page of the process (how many substances created and destroyed, etc). Khullah (talk) 03:21, 1 December 2008 (UTC)

"As there is no known mechanism to transport phosphoenolpyruvate from the mitochondrion into the cytosol, the cytosolic enzyme is believed to be the isozyme important for gluconeogenesis."

Lehninger and other texts show PEP transport from the mitochondrial matrix to the cytosol. Is there a reference for the statement above? If not, it should be removed. —Preceding unsigned comment added by Phonecord (talk • contribs) 22:06, 18 August 2009 (UTC)

Um?

In organisms in which glycerol is derived from glucose (e.g., humans and other mammals), glycerol is sometimes not considered a true gluconeogenic substrate, as it cannot be used to generate new glucose. I am not sure I understand. What do you think the butter I eat becomes after removing the fatty acids? --88.75.225.144 (talk) 19:14, 16 July 2010 (UTC)

Fatty Acid Issue

I have been trying to settle the question of whether free fatty acids (FFA) can be used in gluconeogenesis. Our article suggests, in accordance with many of the textbooks that, "Fatty acids cannot be converted into glucose in animals with the exception of odd-chain fatty acids". Biochemistry by Metzler and Metzler, among other sources, confirms this. The text describes the beta oxidation of FFA (with an even number of carbons) to acetyl-CoA (and acetoacetyl-CoA). Acetyl-CoA can, of course, enter the TCA and generate energy, but when there is excess acetyl-CoA, it begins to generate ketone bodies. This text avers that the animal body has an "inability to form the glucose precursors, pyruvate or oxaloacetate, from acetyl units..." which can lead to ketosis (the formation of ketone bodies from the excess acetyl). This seems to be the basis for the ubiquitous claim that FFA cannot be converted to glucose. However, a bit later on in the text, it is noted that acetone (one of the ketone body species formed from the oxidation of FFA) can be converted through a series of steps to pyruvate. In addition, another pathway is present for the conversion of acetone to pyruvate via 1,2-propanediol. The book than says, "As much as two thirds of this [acetone] may be converted to glucose". Hmm? Is this a splitting of hairs issue? It seems to me that while a FFA with an even number of carbons cannot directly be used in gluconeogenesis, it can be oxidized to acetyl-CoA which can be converted to ketone bodies, which can be used in gluconeogenesis. I found a paper that confirms this. (see edits) In addition, it looks like this question is a longstanding one in biochemistry, so I have amended the article to reflect some of the research.Michaplot (talk) 14:07, 11 September 2010 (UTC)

Formation of carbohydrate from fats - from gluconeogenesis?

There seem to be a bit of confusion about whether "fats" in general can be converted into glucose by this process. My college and I had a discussion that we have been taught that only protein takes part in gluconeogenesis...but the following book Guyton & Hall, Textbook of Medical Physiology|year, 2000, 10th Edition| pages=780, has the following headline in bold

Formation of carbohydrates from proteins and 'fats - gluconeogenesis

In terms of fat, it is later referred to the glycerol portion excluding the fatty acid - now can someone help me define the fat in this context? Is it the fat found in vegi oil and french fries - those are cholesterol => steroids? Also is fatty acid part of fat? Please help me clarify this aspect. Flowright138 (talk) 07:47, 18 September 2011 (UTC)

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Disputed Frontline Image

The current image: https://upload.wikimedia.org/wikipedia/commons/6/6b/Gluconeogenesis.png shows glycolysis as part of gluconeogenesis, which is incorrect. As mentioned in the above discussion for Disputed Image (on the prior image), gluconeogenesis is the reverse pathway of glycolysis, although there are differences in participating enzymes. I personally quite like the libretext image comparing the two: https://chem.libretexts.org/@api/deki/files/126125/Glycolysis_overview.svg?revision=1&size=bestfit&width=543&height=851 I'm not quite sure on the licensing yet for this image and will follow up later. Leaving a note for now. — Preceding unsigned comment added by 2601:246:CD80:7790:C52:AB7C:19E2:A841 (talk) 14:55, 29 March 2021 (UTC)