Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
35 Cards in this Set
- Front
- Back
|
What is the key function of the tca cycle
|
allows the oxidation of common metabolic intermediates to CO2 and H2O in a manner that allows the energy to be captured by NADH, FADH2, and GTP
|
|
|
One full turn of the TCA cycle converts how many carbons to CO2?
|
2 (note that they are not those most recently from acetyl CoA)
|
|
|
Where does the TCA cycle take place
|
in the mitochondrial matrix
|
|
|
What is the role of citrate synthase in the TCA cycle? Which product is favored
|
Catalyzes the condensation of incoming acetyl CoA with OAA. The equlibrium lies highly to isocitrate because of hydrolysis of the thioester bond
|
|
|
In the second step of the TCA cycle citrate is converted to____ via___. Where is the equilibrium?
|
Citrate is converted to cis aconitate and then imediately rehydrated to isocitrate. The equilibrium constnat is ~1.
|
|
|
What is the purpose of the aconitase reaction?
|
Aconitase moves the hydrodroxyl group from the C3 of citrate to the C2 position. This is necessary because the C3 OH of citrate cannot be oxidized to a ketone but once it is isomerized, the oxication can take place.
|
|
|
An important structural feature of the aconiate enzyme active site is...
|
iron sulfur center, helps position the substrate, vulnerable to oxidative stress
|
|
|
What happens after citrate isomerized to isocitrate by aconitase?
(What is made next, what enzyme does it?) |
Isocitrate is converted to aKG by isocitrate dehydrogenase
CO2 is lost and NADH is made |
|
|
What type of reaction is the isocitrate dehydrogenase reaction (isocitrate=>aKG)? What cofactors are involved?
|
This is the first oxidative decarboxylation step of the TCA cycle. The OH group on the C2 of isocitrate is oxidized to the carbonyl group of aKG. NAD is converted to NADH., CO2 is lost.
|
|
|
In which direction does the equilibrium of the isocitrate dehydrogenase reaction lie?
|
The reaction is driven forward (to aKG) because CO2 is lost.
|
|
|
aKG is converted to ___ via____
|
aKG is converted to sucinyl CoA by aKG dehydrogenase. This is the second oxidation of the TCA cycle
CO2 is lost and NADH is produced |
|
|
What type of reaction is the aKG dehydrogenase rxn (aKG=>succinyl CoA) What cofactors are invovled
|
the aKG reaction is an oxidative decarboxylation. NAD is converted to NADH and CO2 is lost
The rxn is similar to the PDH complex so TPP, FAD, and lipoic acid act as cofactors.Thamine (vitamin) is necessary for this to occur similate to PDH and trasketolase |
|
|
What are the substrates of the aKG dehydrogenase reaction
|
CoASH, NAD, aKG
|
|
|
Succinyl CoA is converted to___ via ___
|
Succinyl CoA is converted to succinate viat succinyl coA synthetase
This is an SLP reaction |
|
|
What type of reaction is the succinyl CoA synthetase raction
|
SLP
The high energy bond of succinyl-CoA is used to make GTP, succinate is the product |
|
|
How far carn the carbons originating in acetyl CoA be trakced? Why is this so?
|
They can be tracked until succinyl CoA but succinate has a plane of symmetry between C2 and C3 so the two ends cannot be distinguished. All we know is that in each succinate, one carboxylate is from C1 of acetyl CoA and one CH2 group is from the methyl group of acetyl CoA
|
|
|
Succinate is converted to ___ via ____
|
Succinate is converted to fumarate via succinate dehydrogenase.
This is an oxdation that produces FADH2. Note that succinate dehydrogenase is complex II of the ETC |
|
|
How does succinate dehydrogenase differet "geographically" from the other enzymes of the TCA cycle
|
succinate dehydrogenase is located in the inner mitochondrial membrane whereas the other enzymes are in the matrix
|
|
|
Fumarate is converted to ___ via____
What type of reaction is this? |
fumarate is converted to malate via fumarase
This is a hydration, it adds an OH across the double bond of fumarate to set up for the oxidation back to OAA> |
|
|
Malate is converted to ___ via
what type of reaction is this |
malate is converted to OAA via malate dehydrogenas
this is an oxidation that produces NADH |
|
|
The equilibrium of the malate dehydrogenase reaction is unfavorable in the direction needed for the TCA cycle. How is this overcome
|
Reaction of OAA with incoming acetyl-CoA pulls the reaction forward
|
|
|
What are the oxidative steps of the TCA cycle
(what kind are they and what do they make?) |
4 total
-2 oxidative decarboxylations that make NADH: isocitrate dehydrogenase and aKG dehydrogenase -1 makes FADH2: succinate dehydrogenase -1 makes just NADH:malate dehydrogenase |
|
|
Which step of the TCA cycle is SLP
|
succinylCoA sythetase,
succinyl-CoA=> succinate, makes GTP |
|
|
What role does prochirality play in the TCA cycle/ what did we figure out from this
|
-it was shown that only succinyl CoA is formed even through acetyl CoA and OAA would be expected to be both acetyl CoA and CO2
-we figure out the the TCA enzymes can distinguish prochiral groups -the molecule is prochiral in the eyes of the enzyme |
|
|
What are the key regulated steps of the TCA cycle
|
1. Citrate synthase
2. Isocitrate dehydrogenase 3. aKG dehydrogenase (the committed step and the irreversible oxidative decarboxylations) Note that PDH complex while not part of the TCA cycle is a key step of upstream regulation |
|
|
How is citrate synthase regulated? What inhibits it
|
It is inhibited by ATP, NADH, and succinyl-CoA in vitro but the main physiological control is believed to be the availibility of OAA (the concentration of OAA is usually lower than its Km for citrate synthase)
|
|
|
How is isocitrate dehydrogenase regulated
What inhibits What activates |
This is the key regulated step of the TCA cycle
inhibited by ATP and NADH activated by ADP and AMP |
|
|
Although several steps of the TCA are regulated, the key regulated step is
|
isocitrate dehydrogenase
|
|
|
How is aKG dehydrogenase regulated?
Inhibited? Activated? |
inhibited by ATP, GTP, NADH, and succinyl CoA (latter 2 are products)
ATP and GTP signal the cell has enough energy |
|
|
List 4 sources of acetyl CoA for the TCA cycle
|
1. PDH complex
2. FA oxidation 3.AA's 4. ethanol |
|
|
Explain how alcohol consumption an lead to hypoglycemia
|
Alcohol is oxidied to acetyl CoA which goes to the TCA cycle. As alcohol is oxidized, it uses alot of NADH which interferst ith glycolysis. Since alcohol is a 2 carbon molecule, it cannot maintain blood glucose
|
|
|
List four reactions that can deplete TCA cycle intermediates. Which intermediate do they deplete
|
1. Gluconeogenesis-OAA is converted to malate and sent out
2. Lipid biosynthesis-citrate is transported to the cytosol 3. AA synthesis-uses OAA and aKG 4. Porphyrin biosynthesis-requires succcinyl-CoA |
|
|
name 4 reactios that can replenish TCA cycle intermediates. Where do they feed in?
|
1. Pyruvate carboxylase convertes pyruvate to OAA
2. AA degradation feds into multiple points 3. Odd chain and branched FA's are metabolized to succinyl-CoA 4. purine nucleotide cycle feds in as fumarate |
|
|
Pyruvate carboxylase catalyzes the formation of OAA from pruvate. The fate of the OAA depends on the energy of the cell. Explain where the OAA goes in both the low and high energy state
|
1. Low ATP/ADP= OAA is used in TCA cycle to make more ATP. When ATP/ADP ratio is low due to lack of OAA to do TCA, the build up of acetyl CoA activates pyruvate carboxylase to make more OAA
2. High ATP/ADP. If there is plenty of OAA and acetyl CoA acumulates for anthoer reason, the acetyl CoA will activate pyruvate carboxylase but the OAA will be exported as either malate or aspartate and used for gluconeogenesis. |
|
|
What are the 5 locations of energy capture in the TCA cycle
|
1. isocitrate dehydrogenase (NADH)
2. aKG dehydrogenase (NADH) 3. succinyl CoA synthase (SLP) 4. succinate dehydrogenase (FADH2) 5. malate dehydrogenase (NADH) |
