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104 Cards in this Set

  • Front
  • Back
The Citric Acid Cycle is aka what?
Tricarboxylic Acid Cycle (TCA) or the (Hans) Krebs cycle
The CAC is involved in what kind of metabolism?
Aerobic catabolism
What does the CAC follow?
How much energy did glycolysis capture from glucose? Where does the rest go?
Only about 5% of the total energy in glucose is captured in glycolysis. The leftover energy resides in pyruvate.
? goes into the CAC from glycolysis and it requires ? conditions.
Pyruvate goes into the CAC from glyc. and it reqs AEROBIC conditions.
In stage one of the CAC one molecule of what is removed?
How does pyruvate enter into the CAC cycle?
It is transported from the cytosol into the mitochondria via the pyruvate carrier. Then it is activated by a 3-enzyme complex to become Acetyl-CoA.
What is the ^G'" of stage 1 of the CAC?
-33.4 ( Very Exergonic)
After activation by the 3-enzyme complex, how many of pyruvates carbons are in acetyl CoA?
Two of pyruvate's 3 carbons end up in Acetyl-CoA.
How many enzymes are involved in stage 1 of the CAC?
How many cofactors are involved in stage 1 of the CAC?
5 cofactors are involved:

1. TPP (from thiamine)

2. FAD (from riboflavin)

3. Coenzyme A (CoA, from pantothenate)

4. NAD (from niacin)

5. Lipoate

The first 4 are B vitamins. Lipoate is not a vitamin because we synthesize it ourselves.
A deficiency in what vitamins interferes with the CAC cycle?
The B vitamins which include : Thiamine, Riboflavin, Panthothenate, and Niacin. These must be taken into the body from outside sources.
Where does the CAC take place in the cell?
In eukaryotes it occurs in the mitochondria and in prokaryotes it occurs in the cytosol.
Coenzyme A is a ? : A ? ? compound.
It is a thioester : A high-energy compound.
How does Coenzyme-A combine with other molecules?
It combines by the Mercapto- group.
Lipoate is aka?
Lipoic acid
Lipoate can be observed in what form?
It can be in either an oxidized or reduced form.
What does lipoate have the ability to do?
It can bind an acetyl group in one part of the complex and move it to another part of the complex.
What is Arsenite?
It is much more dangerous than arsenAte to a cell. It attaches to lipoate and once bound you cannot get rid of it. Once this occurs you can no longer bind Acetyl CoA. This causes a shutdown of the Kreb's Cycle.
How many enzymes, cofactors, and regulatory proteins are involved in the pyruvate dehydrogenase complex?
5 Cofactors. 3 enzymes. 2 Regulatory proteins.
What is the Pyruvate dehydrogenase complex important for?
It plays a role in substrate channeling. So when the 3 enzymes involved are involved in rxns the product from one rxn becomes the reactant from the next, etc.
Briefly explain the transition from pyruvate to acetyl CoA? (ie. What goes in and what comes out of cycle?)
Co-enzyme A and NAD+ enter into the cycle.

Acetyl Co-A (Co-enzyme bound to an acetyl group) and NADH (with energy captured) come out.
What is the problem with the oxidative decarboxylation of pyruvate?
A LACK OF THE VITAMIN THIAMINE in the diet can result in problems with this rxn (esp. in the brain, where aerobic oxidation is very important). It slows down the rxn.
What is a term that refers to a lack of the vitamin thiamine?
What is the net loss or gain of C in the CAC?
No net loss or gain of C. Two in and two out.
What energy do you get from the CAC?
You get 3 NADH, 1 FADH2, and 1 GTP or ATP.
How does oxaloacetate relate to step 1 of the CAC?
It is an intermediate in the matrix of the mitochondria.
What is "spun-off" in the rxn between Acetyl-CoA and Oxaloacetate in step 1 of the CAC?
Co-enzyme A
What is the ^G'" of the 1st step of the CAC? For what reason is this important?
-32.2. It is very exergonic and is important in moving the process along.
What is the net loss or gain of step 2 of the CAC?
There is no net loss or gain.
What is the ^G'" of the 2nd step of the CAC? What does this infer about this step?
+13.3. It is an endergonic process, so energy is required. It proceeds because it is coupled to step 1 and step 3 which are both exergonic. When this is taken into consideration it indicates that the ^G is probably actually around 0.
What is effectively reversed in step 2 of the CAC?
The H and OH of the citrate molecule (reactant) reverse in the isocitrate molecule (product).
What is formed in the 3rd step of the CAC? (energy-wise)
What is one NADPH approximately equivalent to?
It is basically equivalent to 1 NADH equivalent in energy.
What is the ^G'" of the 3rd step of the CAC?
It is -20.9; this step is exergonic even though it synthesizes NADPH.
Besides NADPH, what else is released in the 3rd step of the CAC?
What drives rxn 4 of the CAC to move forward?
The alpha-ketoglutarate complex catalyzes it. It is composed of 3 enzymes and 5 cofactors.
What re-enters in step 4 of the CAC?
What is formed in the 4th step of the CAC?
NADH is formed.
Besides NADH what else is formed in the 4th step of the CAC?
What is the ^G'" of the 4th step of the CAC?
The ^G'" of step five of CAC? What can be said about this?
-2.9kj/mol. It is slightly exergonic but it is practically a wash.
What does step 5 of the CAC form?
It forms either ATP or GTP.
What is released in step 5 of the CAC?
Co-A is released again.
Why is Co-A considered a cofactor in CAC?
It is considered a co-factor because it keeps entering and releasing from the CAC cycle.
In step 5 of the CAC, Succinyl-CoA becomes Succinate. What can be said about this?
Step 5 involves a higher energy compound going to a lower energy compound. Or "It is an endergonic hydrolysis of thioester bond coupled to formation of GTP or ATP (which is exergonic)"
What is energy transferred to in step 6 of the CAC?
It is transferred to FADH2. FAD is reduced to FADH2 and captures energy.
What is the ^G'" of step 6 of the CAC?
0 kj/mol
Succinate becomes fumarate in step 6 of the CAC. What can be said about this?
Again, a higher energy compound becomes a lower energy compound. The energy is captured in FADH2.
What does step 7 of the CAC illustrate?
It illustrates stereospecificity in both the recognition of substrate and the formation of product.
Explain how step 7 of the CAC illustrates stereospecificity.
It recognizes Fumarate (trans) but does not recognize Maleate (cis) as a substrate. It also forms L-malate as a product but D-malate is never formed.
What is the ^G'" of step 8 of the CAC?
The standard ^G'" of step 8 of the CAC is is very endergonic. Explain how the CAC cycle is still able to proceed?
The oxaloacetate concentration inside of the cell is actually quite low. This actually causes the ^G to be less endergonic. This along with the fact that it is coupled with the next reaction in the cycle (which is step one and is very exergonic) allows it to proceed.
What is energy transferred to in step 8 of the CAC?
In the reaction; 2 pyruvate -> 2 Acetyl CoA; what is formed? Explain.
2 NADH are directly formed but ultimately 5 ATP are formed. Every molecule of NADH and FADH2 can be converted into ATP energy (and they will be).
Give the conversion ratios of energy transformation from NADH and FADH2 to ATP.
2 NADH becomes about 5 ATP. 2 FADH2 becomes about 3 ATP.
What is the energy in ultimate ATPs produced by glycolysis?
What is the energy in the form of NADH that is formed from glycolysis? How many ATPs does this produce ultimatlely?
2 NADH. It yields about 3-5 ATP.
How many G/ATP are produced by the CAC? How many ATPs does this ultimately produce?
2 G/ATP. This results in 2 ATPs.
How many NADH are produced in the CAC? How many ATPs does this result in ultimately?
6 NADH. This results in about 15 ATP.
How many FADH2 are produced in the CAC? How many ATPs does this ultimately produce?
2 FADH2. This leads to 3 ATP ultimately.
How many ATP equivalent do you get in total from the combined metabolism of Glycolysis and the CAC?
You get about 30-32.
? metabolism of glucose yields about 5 times as much ATP as ?. (30-32 vs. 5-7)
Aerobic metabolism yields more than anaerobic.
The CAC also plays a role in anabolism. What does this indicate?
It indicates that the CAC generates compounds. It is not just for the purpose of getting energy out.
Metabolic pathways have much overlap between different cycles. Give an example of how this is illustrated in the CAC.
Bypass number 1 from gluconeogenesis is involved in the CAC. This is the reaction that involves pyruvate and oxaloacetate that bypasses step 10 of glycolysis.
Alpha-ketoglutarate (an intermediate in the CAC) is involved in a side reaction that produces glutamate. What does this rxn go on to be involved in?
It is involved in the metabolism of a.a.s.
What is an Amphibolic pathway? Give an example.
It is a pathway that displays catabolic and anabolic roles. An example is the CAC.
What is an Anaplerotic reaction?
It is a rxn that replenishes intermediates when they are removed to become precursors of other molecules.
How many Anaplerotic reactions are involved in the CAC?
There are 4 anaplerotic reactions. You are not required to memorize them but it is key to know that :

1. Malate is from Pyruvate

2. OAA is from Pyruvate or PEP

(These 2 key notes basically summarize all 4 reactions, see slide # 26)
What is typically occuring during the 4 anaplerotic rxns of the CAC? What is an example of this?
Typically a 4 C molecule receives a Bicarbonate group to make a 5 C molecule. Biotin is an example of this.
What is Biotin?
It is a B vitamin. So it is attained from diet. It is also a cofactor for several CAC anaplerotic reactions. It transfers CO2 from HCO3- to other molecules.
How many anabolic side reactions is the CAC involved in?
What are the 4 methods of regulation?
1. By substrate

2. By product

3. Allosteric

4. Covalent
How is substrate concentration related to the regulation of a reaction?
The higher the [substrate] the higher the more exergonic the reaction will be. Will cause a more negative ^G.
How is product concentration related to the regulation of a reaction?
The higher the [product] the more endergonic a reaction will be. Will cause a more positive ^G.
How is a reaction regulated allosterically?
It involves some molecule acting on an enzyme.
How is a reaction regulated covalently?
It involves the addition or removal of a component by enzyme to either speed up or slow down the reaction.
Which steps (rxns) of the CAC are allosterically regulated?
The Lead-in reaction, plus steps 1, 3, and 4.
What are the allosteric inhibitors of the reaction that leads into CAC?
1. Acetyl-CoA (This is a PRODUCT of the CAC and feeds back)

2. ATP and NADH (these are ENERGY products that inhibit once there is a sufficient amount)
What are the "allosteric activators" or the reaction that leads into the CAC?
1. CoA and NAD+ (These are considered SUBSTRATES that activate the rxn)

2. AMP, and NAD+ (These signify LOW ENERGY)

3. Ca++ (specifically in muscle tissue)
What are the allosteric inhibitors of step 1 of the CAC?
1. Citrate, Succ. CoA (A PRODUCT INH)

What are the "allosteric activators" of step 1 of the CAC?
What are the allosteric inhibitors of step 3 of the CAC?
What are the allosteric activators of step 3 of the CAC?

2. Ca++
What are the allosteric inhibitors of step 4 of the CAC?

What are the allosteric activators of the 4th rxn of the CAC?
What does increased substrate concentration do to a reaction?
It moves the reaction forward.
What does increased product do to a reaction?
It slows a rxn down.
What do increased energy molecules do to a reaction?
They slow it down.
What does decreased energy do to a reaction?
It moves the reaction forward.
It is important to remember what CAC is ultimately doing. What is that?
It is turning energy from pyruvate into ATP and NADH which is usable by a cell.
The regulation of the feed-in step by pyruvate dehydrogenase is an example of what?
It is an example of COVALENT modification.
What does the regulation of the feed-in step by covalent modification involve?
3-enzymes, 5-cofactors, 2-regulatory molecules
What are the two regulatory molecules that are involved in covalent modification of the feed-in step (Pyruvate Dehydrogenase) of the CAC?
1. Kinase

2. Phosphatase
Which form of pyruvate dehydrogenase is active?
When it is dephosphorylated it is active. Phosphorylated is inactive.
What activates Pyruvate dehydrogenase?
Phosphatase. It dephosphorylates the enzyme, making it active.
What inactivates Pyruvate dehydrogenase?
Kinase. It phosphorylates it; making it inactive.
What activates Kinase?
ATP activates kinase. Kinase then goes on to inactivate pyruvate dehydrogenase by phosphorylating it.
Pyruvate dehydrogenase is similar to ? ? and the opposite of ? ?.
It is similar to Glycogen synthase and the opposite of Glycogen phosphorylase.
What methods of regulation are involved in CAC regulation?
Allosteric and Covalent
What is the Glyoxylate Cycle?
It converts Fatty Acids and Amino Acids into Carbohydrates. This occurs in PLANTS ONLY because WE CAN NOT CONVERT FAs INTO CARBS. However, we can convert carbs into FAs.
What is the ultimate product of the Glycoxylate cycle?
What begins the glyoxylate cycle?
What is added into the Glycoxylate cycle?
Acetyl-CoA is added into the cycle twice.