Practice - Gluconeogenesis: Videos & Practice Problems

3-phosphoglycerate kinase is a key enzyme in both glycolysis and gluconeogenesis, generating ATP from ADP. Glycolysis features irreversible steps, requiring distinct enzymes for gluconeogenesis, such as fructose 1,6-bisphosphatase, which counteracts phosphofructokinase. The conversion of pyruvate to phosphoenolpyruvate involves two steps, consuming ATP and GTP. Tight regulation prevents futile cycles between glycolysis and gluconeogenesis, ensuring energy efficiency. Understanding these pathways is crucial for grasping metabolic control and energy production in cells.

Practice - Gluconeogenesis

If you haven't answered question 31 yet, pause the video now. An enzyme that is used by both glycolysis and gluconeogenesis is 3-phosphoglycerate kinase. This is the first enzyme in the glycolytic pathway to generate ATP from ADP, and this is the enzyme that takes 1,3-bisphosphoglycerate and turns it into 3-phosphoglycerate; in the process, it generates an ATP. This is step number 7 of glycolysis. Now, these other enzymes are restricted to one pathway. Phosphofructokinase 1 is step 3 of glycolysis. Hexokinase is step 1 of glycolysis, and pyruvate kinase is step 10 of glycolysis. Glucose-6-phosphatase is the last step of gluconeogenesis, and that is the enzyme that removes the phosphate group from glucose and is only present in liver cells, you might recall. Now, an enzyme used in gluconeogenesis that reverses the action of the glycolytic enzyme phosphofructokinase is fructose-1,6-bisphosphatase. And you might remember the whole pattern of phosphatases reversing the action of kinases. Phosphofructokinase produces fructose-1,6-bisphosphate in the third step of glycolysis. And so fructose-1,6-bisphosphatase undoes the action of phosphofructokinase and actually removes a phosphate group from fructose-1,6-bisphosphate.

Moving on to question 33, which of the following statements about gluconeogenesis is false? And the answer is that it consists entirely of glycolytic enzymes that are reversible. Remember, there are those 3 glycolytic reactions that cannot be reversed. And so we have to use different enzymes. And actually, it takes 4 reactions to undo those 3 because the last reaction of glycolysis, that of pyruvate kinase, has to be undone by 2 reactions in gluconeogenesis.

And speaking of that, let's move on to question 34 because pyruvate cannot be directly converted to phosphoenolpyruvate, right? That's where pyruvate kinase takes phosphoenolpyruvate and turns it into pyruvate and we have to undo that in 2 steps in gluconeogenesis. So first, we have to convert pyruvate to oxaloacetate. B is actually wrong though because it costs an ATP and a GTP. Remember that converting oxaloacetate to phosphoenolpyruvate costs GTP, not ATP. C is also correct though. The reason that we have to undo it in 2 steps is that the action of pyruvate kinase is so energetically favorable, it cannot simply be undone by one reaction. So, the answer here is actually E both A and C.

Now, the last question about gluconeogenesis is, why are glycolysis and gluconeogenesis so tightly controlled? What's the point of all this? And the point is to prevent a futile cycle. If gluconeogenesis and glycolysis could occur at the same time, they would just undo each other, right? We'd be wasting energy because glycolysis goes in one direction, gluconeogenesis goes in the other. We would just be flip-flopping. We'd just be pointlessly carrying out reactions. We wouldn't actually be producing any products really from either reaction because the products of one reaction are the substrates of the other and they just kind of be flip-flopping back and forth. So, when glycolysis is in action, gluconeogenesis is not happening and when gluconeogenesis is in action, glycolysis is not happening. Remember that most of the enzymes are readily reversible between those two reactions and they're also shared by those two reactions. So, really, it's just controlling the few enzymes that carry out the irreversible steps that allow you to regulate glycolysis and gluconeogenesis.

Alright, let's flip the page and finish up with some questions on the pentose phosphate pathway.

Here’s what students ask on this topic:

What is the role of 3-phosphoglycerate kinase in glycolysis and gluconeogenesis?

3-phosphoglycerate kinase is an enzyme that plays a crucial role in both glycolysis and gluconeogenesis. In glycolysis, it catalyzes the conversion of 1,3-bisphosphoglycerate to 3-phosphoglycerate, generating ATP from ADP in the process. This reaction is part of step 7 in glycolysis. In gluconeogenesis, the enzyme works in the reverse direction, converting 3-phosphoglycerate back to 1,3-bisphosphoglycerate, utilizing ATP. This dual functionality makes 3-phosphoglycerate kinase a key player in cellular energy metabolism.

Why are glycolysis and gluconeogenesis tightly regulated?

Glycolysis and gluconeogenesis are tightly regulated to prevent a futile cycle, where both pathways would run simultaneously and cancel each other out, wasting energy. This regulation ensures that when glycolysis is active, gluconeogenesis is inhibited, and vice versa. The control is mainly exerted on the irreversible steps of these pathways, which involve distinct enzymes. This tight regulation is crucial for maintaining energy efficiency and metabolic balance within the cell.

Which enzymes are unique to gluconeogenesis and not found in glycolysis?

Several enzymes are unique to gluconeogenesis and are not found in glycolysis. These include glucose-6-phosphatase, which catalyzes the final step of gluconeogenesis, converting glucose-6-phosphate to glucose. Another key enzyme is fructose-1,6-bisphosphatase, which reverses the action of phosphofructokinase-1 by converting fructose-1,6-bisphosphate to fructose-6-phosphate. Additionally, pyruvate carboxylase and phosphoenolpyruvate carboxykinase (PEPCK) are involved in converting pyruvate to phosphoenolpyruvate (PEP) in a two-step process, bypassing the irreversible pyruvate kinase step in glycolysis.

How is pyruvate converted to phosphoenolpyruvate (PEP) in gluconeogenesis?

In gluconeogenesis, pyruvate is converted to phosphoenolpyruvate (PEP) through a two-step process. First, pyruvate is carboxylated to oxaloacetate by the enzyme pyruvate carboxylase, a reaction that requires ATP. Then, oxaloacetate is converted to PEP by phosphoenolpyruvate carboxykinase (PEPCK), which uses GTP as an energy source. This two-step process is necessary because the direct reversal of the pyruvate kinase reaction in glycolysis is energetically unfavorable.

What is the function of fructose-1,6-bisphosphatase in gluconeogenesis?

Fructose-1,6-bisphosphatase is a key enzyme in gluconeogenesis that catalyzes the conversion of fructose-1,6-bisphosphate to fructose-6-phosphate. This reaction is the reverse of the phosphofructokinase-1 (PFK-1) step in glycolysis, which converts fructose-6-phosphate to fructose-1,6-bisphosphate. By removing a phosphate group, fructose-1,6-bisphosphatase helps bypass the irreversible PFK-1 step, allowing gluconeogenesis to proceed and produce glucose from non-carbohydrate precursors.