Lecture 8 Flashcards
What are the regulatory enzymes and thus, the irreversible steps of the pathway?
Citrate synthase, Isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase complex.
What can all enter the citric acid pathway?
carbs, amino acids, and fatty acids.
Which intermediates undergo a oxidative decarboxylation reaction in the citric acid cycle?
Isocitrate and alpha-ketoglutarate. At both of the these steps CO2 is release and NADH is made.
Which intermediate goes through substrate-level phosphorylation?
Succinyl-CoA converting to Succinate creates GTP from GDP in the process. And depending on the isoform of Succinyl-CoA it can create ATP from ADP.
Where does the energy come from in step 5 of the citric acid cycle to make ATP?
The energy comes from the Thioester bond. Similar to Pyruvate Dehydrogenase Complex, Alpha-Ketogluterate Complex will create a thioester bond. Alpha-Ketogluterate Complex will produce succinyl-CoA instead of acteyl-CoA.
Redox reaction gave energy to the thioester bond and the thioester bond gave energy to create ATP or GTP.
Complex II in the Electron Transport Chain is also called what in the citric acid cycle?
Succinate Dehydrogenase. The citric acid cycle - one of the enzyme is the same enzyme in the ETC. The FADH2 from succinate deyhdrogenase never leves itself and passes electrons through itself.
Oxaloacetate is in high or low concentration?
Very low concentration in the matrix of the mitochondria (only 50 to 70 molecules). The reason why is because the reaction catalyzed by malate dehydrogenase is +29 kl/mol. Because oxaloacetate is so low, the energy in Acetyl-CoA is used to drive the reaction.
*What would happen to the rate of the citric acid cycle if malate/OAA was siphoned off for glucose production?
A) It would go up
B) It would go down
C) It would not change
B) It will go down. This is important because there are a lot of things that will take away from the citric acid cycle. And this reduces the pool or concentration of the intermediates in the citric acid cycle. There are two different types of process that affect this.
What are Cataplerotic reactions? What are Anaplerotic reactions? And what are the examples?
cataplerotic- Removing intermediates from the pathway. This will reduce flux through the pathway.
Ex: Citrate can be removed from the citric acid cycle to make fatty acids.
And anaplerotic reaction?- Give back to the pathway. INcrease Flux - INcrease OAA.
Ex: Pyruvate Carboxylase will make Oxaloacetate from Pyruvate, PEP, Pyruvate can be made into Malate. Glutamine can be used to make glutamate, and glutamate can be used to make alph-ketoglutarate.
*Would the production of acetyl-CoA from fatty acids be “anaplerotic”?
No! Becuase it has to use four carbons in the cycle to get right back to the same four carbons in the cycle.
Both of the carbons from Acetyl-CoA are given off as CO2.
However, anything being converted to Oxaloacetate will however be anaplerotic.
If Fatty Acid Synthesis INcreases, what happens to the Citric Acid Cycle?
Citrate will DEcrease and thus will DEcrease OAA at the end of the pathway– and that will then slow the next reaction of the cycle and reaction of citrate synthase will decrease.
If Citrate synthase reaction decreases then, flux through the whole cycle goes down – Acetyl-CoA will then go up in concentrations. –Pyruvate which can be converted to OAA by Pyrvuate Carboxylase and it turns out that Acetyl-CoA is an allosteric activator of Pyruvate Carboxylase. This will increase OAA by the conversion of Pyruvate to OAA. This help balance the steady state of metabolism.
How does ATP, NADH, ADP/AMP, and NAD+ regulate the citric acid cycle?
ATP and NADH are negative feedback loops.
NAD+ and ADP/AMP are activators of the pathway if ATP is low or there is not enough NADH.
What are the consequences of Citrate being pulled out of the citric acid cycle for fatty acid synthesis?
There will be less citrate then to go through the citric acid cycle to be reused in making OAA. This means that citrate synthase will decrease in activity as there is less OAA to be used to make citrate and this means that Acetyl CoA will accumulate.
This means Flux through the Citric Acid Cycle will go down and even fatty acid synthesis will go down as well.
What happens to Pyruvate Carboxylase when Acteyl CoA concentrations go up?
Aceteyl CoA is an activator of Pyruvate Carboxylase and then this will increase the conversion of pyruvate to OAA to increase flux once again through the Citric Acid Cycle.
That is one example of how the cell maintains steady state flux through the Citric Acid Cycle.
True or False: If anaplerotic reactions increase in the citric acid cycle then cataplerotic reactions will also have to increase in the citric acid cycle.
True. This is how the cell maintains a steady state.
