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Citric Acid Cycle (Test 1)

Terms in this set (59)

What enzyem links glycolysis to the citric acid cycle?
Pyruvate Dehydrogenase. (PDH)

Converting Pyruvate to Acetyl CoA
What is PDH inhibited by?
Acetyl CoA
NADH
Low Insulin Concentration
What stimulated PDH?
Insulin
NAD+
Calcium
Amphibolic
Both Catabolic and Anabolic!
Why is the citric acid cycle Amphibolic?
because it serves both degrative and synthetic roles!

Catabolism and Anabolism.
What are the citric acid cycle's catabolic activities?

(Important for the breakdown of fuels)
Oxidize 2 carbon atoms of Acetyl CoA to CO2

And thus generates compounds that will provide most of the cells energy via oxidative phosphorylation:
NADH x3
FADH x1
And reduced cofactors
What are the TCA anabolic activities?

(hint: Produces precursors)
Makes the starting materials for synthesis of glucose, heme, fatty acids, amino acids:
Citrate
α-ketoglutarate
Succinyl CoA
Oxaloacetate
(These are all INTERMEDIATES in the TCA cycle)
The TCA cycle intermediate α-ketoglutarate, which is a precursor for what?
Glutamate
The TCA cycle intermediate Succinyl CoA, which is a precursor for what?
Carbon for Heme synthesis
The TCA cycle intermediate oxaloacetate, which is a precursor for what?
Aspartate
The TCA cycle intermediate citrate, which is a precursor for what?
Carbon for fatty acid synthesis and controls glycolysis via PFK
Is the citric Acid cycle aerobic? Anaerobic? Or both?
Strictly! Aerobic

Why? Because it's dependent on ETC for NAD+ and FAD which can only happen if there is oxygen present.
Pyruvate Carboxylase makes _________ from _________?
Pyruvate carboxylase makes oxalocacetate from pyruvate +CO2 +ATP

Pyruvate +ATP +CO2 ------>. Oxaloacetate
[Pyruvate carboxylase]
Why is Pyruvate carboxylase important for the TCA cycle even though oxaloacetate is only an intermediate, and therefore NOT used up in the cycle?
Pyruvate carboxylase has to keep making more because the intermediate oxaloacetate gets removed by other stuff for other stuff.
what are the 3 controls of the Krebs cycle?
1. Availability of Acetyl CoA

2. Availability of O2

3. Energy charge (proportion of ATP and ADP and AMP)

4. Increase in NAD+ = Increase in TCA
Increase in NADH = decrease in TCA
What are the other names for the Citric Acid Cycle?
TCA, Krebs
What is the fuel for the citric acid cycle?
Acetyl CoA, NAD+ and FAD
From what metabolites is the fuel for the Krebs cycle derived?
Acetyl CoA is the fuel. It is derived from the breakdown of FA's, AA,s and glucose. Soooooo basically Glycolysis.
Where in the cell does the TCA cycle take place?
In the matrix mitochondria
What is the first step of the TCA cycle?
Acetyl CoA + Oxaloacetate + H2O ------------> Citrate

Citrate Synthase
How many reduced cofactors are produced by the oxidation of 1 molecule Acetyl CoA by the TCA cycle?
3xNADH
1xFADH2
What other high energy compound is generated by the TCA cycle?
GTP!

NOT ATP
Is ATP generated by the TCA cycle? If so, how much?
NO!
Why is Pyruvate carboxylase important to the TCA cycle?
Provides another means of adding carbons into the TCA cycle other than Acetyl CoA.

Adds carbons by generating oxaloacetate from Pyruvate.
What is Pyruvate carboxylase's allosteric effector?
Acetyl CoA
Why is PDH important?
Makes Acetyl CoA from Pyruvate in the mitochondria. It also releases energy in the form of NADH.



"Dehydrates Pyruvate".
Where does the "H" go? It goes to NADH!
The oxidation of one mole of glucose via glycolysis and c.a.c produces how many moles of ATP if you could GTP as ATP?
1mole glucose = about 30 moles ATP.
What does Acetyl look like?
CoA-S-C=O
I
CH3
What process oxidizes Acetyl CoA?
Citric Acid Cycle.
We lose a carbon at which two steps?
Isocitrate 6C ----> alpha-ketogluterate 5C

alpha-ketogluterate 5C ----> Succinyl CoA 4C
How many carbons does alpha-ketogluterate have?
5 carbons.
COO-
C=O
Ch2
Ch2
COO-
What does oxaloacetate look like?
COO-
C=O
Ch2
COO-
What enzyme helps Acetyl CoA + Oxaloacetate to become Citrate?
Is it spontaneous?

Acetyl CoA + Oxaloacetate -----> Citrate

(Step 1)
Citrate Synthase!

Of course it's spontaneous!
What catalyzes the reaction of isocitrate to alpha-ketogluterate?

3rd step of TCA cycle
Isocitrate dehydrogenase

(This step also takes away a carbon in CO2)
What catalyzes the reaction of
Citrate ----------> isocitrate?

Step 2
Citrate -------> Isocitrate
Aconitase

I "CON TASTE" an orange. And after biting it, it's a different shape! Aconitase
AlphaKeto ---------> Succinyl CoA

What enzyme catalyzes this reaction?

Step 4
AlphaKetogluterate Dehydrogenase
What step in the TCA cycle makes GTP?
Succinyl CoA -------> Succinate

Using Succinate Thiokinase (Succinyl CoA Synthetase)
Succinyl CoA ----------> Succinate

What enzyme catalyzes this reaction?
Succinate Thiokinase
Succinate -----> Fumerate

What enzyme catalyzes this reaction?
Succinate Dehydrogenase

(Takes away 2 Hydrogens)
(Makes FADH2)
Which step in TCA cycle makes FADH2?
Succinate -----> Fumerate

By Succinate Dehydrogenase.

Remember it takes 2 Hydrogens away from Succinate
Fumerate ------> Malate

What enzyme catalyzes this reaction?
Fumerate Hydratase

Adds an OH using Water.
Malate -------> Oxaloacetate

What enzyme catalyzes this reaction?
Malate dehydrogenase of course!
Where are ALL of the enzymes used in the TCA cycle?
Mitochonria!
Is Pyruvate Converted to Acetyl CoA inside or outside the mitochondria.

Hint: all of glycolysis occurs in the cytosol
PDH converts Pyruvate to Acetyl CoA in the mitochondria. this is NOT part of the TCA cycle.

Haha! it was a bad hint!
Which cycle is PDH apart of?

Hint: It's in the mitochondria where the Kreb cycle occurs.
Trick question! It is not a part of any cycle!

It convert Pyruvate to Acetyl CoA, in between glycolysis and TCA cycle.
Which metabolic process is Pyruvate Carboxylase part of?

Hint: this quizlett is about the Kreb's cycle.
Bad hint! It's a trick!

Pyruvate Carboxylase turns Pyruvate into Oxaloacetate. This is used as the first step in Gluconeogenesis OR Krebs cycle.
Where is PDH?
Mitochondria
Where is citrate found?

What does citrate do?
lives inside and outside the mitochondria

Inside - intermediate in TCA

Outside - carbon for fatty acid synthesis and
INHIBITS glycolysis (via PFK-1)
What does alphaketogluterate participate in?
In mitochondria - intermediate for TCA
Also lives outside of the TCA cycle.

glutamate by transamination.
What does Succinyl CoA, glycine, Iron make?
Heme
What role does Succinate play in the retina?
Succinate produced in the mitochondria control vascular proliferation.

Succinate receptor GPR91 in neurons plays a major role in retinal angiogenesis
Oxaloacetate
Participates in glucose synthesis and Gluconeogenesis.

Aspartate by transamination
What does anaplerosis mean?
"To fill up"

Anaplerosis is the act of replenishing TCA cycle intermediates that have been extracted for biosynthesis
What probably governs the speed of the TCA cycle?
Isocitrate dehydrogenase
How does O2 impact the TCA cycle?

What direct role does it play in the TCA cycle?
IT PLAYS AN INDIRECT ROLE! Not a direct role!

It is the final electron accepter of the ETC, which replenishes the fuel for the TCA cycle. Without Oxygen, the TCA cycle could not continue.
INDIRECTLY!
What are the starting reactants and ending products in the TCA cycle?
(Summary)
Acetyl CoA, 3NAD+, 1FAD, GDP, Pi.

----------------------->

2CO2, 3NADH, 1FADH2, 1GTP, CoASH, 3H+
Pathology.
What two enzymes are linked to mitochondrial dysfunction and cancer?
Succinate dehydrogenase and
Fumerate Hydratase.
Accumulated Succinate or Fumerate inhibit hydroxyl action a of proline on hypoxia-inducible factors (HIF's), which leads to what?
Cell proliferation and angiogenesis
Cell proliferation and angiogenesis can be caused by the accumulation of what two intermediates in the TCA cycle?
Succinate and Fumerate
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