The Krebs cycle plays a central role in our metabolism. In all the classes I give about metabolism, the Krebs cycle is present...
As I mentioned in previous posts, this process is composed by 8 steps, 3 of which are catalyzed by regulatory enzymes. These enzymes are citrate synthase (1st reaction), isocitrate dehydrogenase (3rd Reaction) and alpha-ketoglutarate dehydrogenase (4th reaction).
In this post I will talk a little about the main activators and inhibitors of each. As you will see, there are many modulators that are common to more than one enzyme, which makes life easier for those who have to study this metabolic pathway. :)
Citrate synthase:
As I mentioned in previous posts, this process is composed by 8 steps, 3 of which are catalyzed by regulatory enzymes. These enzymes are citrate synthase (1st reaction), isocitrate dehydrogenase (3rd Reaction) and alpha-ketoglutarate dehydrogenase (4th reaction).
In this post I will talk a little about the main activators and inhibitors of each. As you will see, there are many modulators that are common to more than one enzyme, which makes life easier for those who have to study this metabolic pathway. :)
Citrate synthase:
Inhibitors
Succinyl-CoA - it is an intermediate of Krebs cycle. More specifically, it is the 4th intermediate of Krebs cycle, that means, it is formed in a reaction after the reaction that we are considering. So if we have an accumulation of intermediates formed in further reactions, it makes sense that these may inhibit the initial reactions of the pathway in question, in this case the first.
Citrate - it is the product of the reaction, so it makes sense that it might inhibit its own synthesis.
ATP - the Krebs cycle is a catabolic pathway, ie, its main goal is to produce energy (ATP). If the cell already has energy, the process is inhibited.
NADH - The reasoning is equivalent to that made for the ATP. That is, the NADH has a high energy potential, since in cellular respiration it can lead to the production of ATP, therefore it is logical that NADH functions as an inhibitor of Krebs cycle.
Long Chain fatty acid-CoA - it is not completely understood the inhibitory role of the long chain fatty acids in the Krebs cycle, but it is believed that this property is related to the fact that they behave as detergents because they are amphipathic compounds consisting of one polar part (carboxylic group) and one part apolar part (hydrocarbon chain). Oleic acid (18 carbons and one double bond at carbon 9) appears to be the major fatty acid inhibitor of citate synthase.
Activators
ADP - ADP signals an energy deficit in the cell because it is produced when ATP is spent for energy. So it makes sense that it activates the Krebs cycle, because the main objective of this pathway is the production of energy.
Isocitrate dehydrogenase:
Succinyl-CoA - it is an intermediate of Krebs cycle. More specifically, it is the 4th intermediate of Krebs cycle, that means, it is formed in a reaction after the reaction that we are considering. So if we have an accumulation of intermediates formed in further reactions, it makes sense that these may inhibit the initial reactions of the pathway in question, in this case the first.
Citrate - it is the product of the reaction, so it makes sense that it might inhibit its own synthesis.
ATP - the Krebs cycle is a catabolic pathway, ie, its main goal is to produce energy (ATP). If the cell already has energy, the process is inhibited.
NADH - The reasoning is equivalent to that made for the ATP. That is, the NADH has a high energy potential, since in cellular respiration it can lead to the production of ATP, therefore it is logical that NADH functions as an inhibitor of Krebs cycle.
Long Chain fatty acid-CoA - it is not completely understood the inhibitory role of the long chain fatty acids in the Krebs cycle, but it is believed that this property is related to the fact that they behave as detergents because they are amphipathic compounds consisting of one polar part (carboxylic group) and one part apolar part (hydrocarbon chain). Oleic acid (18 carbons and one double bond at carbon 9) appears to be the major fatty acid inhibitor of citate synthase.
Activators
ADP - ADP signals an energy deficit in the cell because it is produced when ATP is spent for energy. So it makes sense that it activates the Krebs cycle, because the main objective of this pathway is the production of energy.
Isocitrate dehydrogenase:
Inhibitors
Succinyl-CoA - the reasoning that was made for the citrate synthase applies in this situation.
ATP - the reasoning that was made for the citrate synthase applies in this situation.
NADH - the reasoning that was made for the citrate synthase applies in this situation.
Activators
ADP - the reasoning that was made for the citrate synthase applies in this situation.
Ca2 + (muscle) - as I mentioned in a previous post, about the regulation of pyruvate dehydrogenase complex, Ca2+ is an intracellular messenger whose concentration increases during muscle contraction. Therefore, in this context contracting cells will require energy, so catabolic processes and, in particular, the Krebs cycle, is activated.
Alpha-ketoglutarate dehydrogenase:
Succinyl-CoA - the reasoning that was made for the citrate synthase applies in this situation.
ATP - the reasoning that was made for the citrate synthase applies in this situation.
NADH - the reasoning that was made for the citrate synthase applies in this situation.
Activators
ADP - the reasoning that was made for the citrate synthase applies in this situation.
Ca2 + (muscle) - as I mentioned in a previous post, about the regulation of pyruvate dehydrogenase complex, Ca2+ is an intracellular messenger whose concentration increases during muscle contraction. Therefore, in this context contracting cells will require energy, so catabolic processes and, in particular, the Krebs cycle, is activated.
Alpha-ketoglutarate dehydrogenase:
Inhibitors
Succinyl-CoA - it is the product of the reaction so, it makes sense that this molecule may inhibit its own synthesis.
ATP - the reasoning that was made for the citrate synthase applies in this situation.
NADH - the reasoning that was made for the citrate synthase applies in this situation.
Activators
Ca2 + (muscle) - the reasoning that was made for isocitrate dehydrogenase applies in this situation.
Succinyl-CoA - it is the product of the reaction so, it makes sense that this molecule may inhibit its own synthesis.
ATP - the reasoning that was made for the citrate synthase applies in this situation.
NADH - the reasoning that was made for the citrate synthase applies in this situation.
Activators
Ca2 + (muscle) - the reasoning that was made for isocitrate dehydrogenase applies in this situation.
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