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biochem 2
chapter 20 + 21
52
Chemistry
Undergraduate 4
04/25/2008

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Term

To understand or describe any pathway or cycle, start with the following paradigm for the TCA cycle.

Names:
Functions:
Substrates:
Products:
control Enzymes:
Regulation:
Compartment(s):
Tissues of interest:
Definition
Term

Name the four dehydrogenase enzymes of the TCA cycle. What are the substrates and products of each reaction?

Definition

[image]

Term

What is the approximate energy yield from the oxidation of one acetyl CoA molecule?

Definition
10 high energy bonds approximataley 70Kcal/mol
Term
Name the enzyme of the TCA cycle that catalyzes a substrate level phosphorylation.
Definition
succinate thiokinase catalyzes GDP to GTP
Term
What is the difference between a substrate level phosphorylation and oxidative phosphorylation?
Definition
O2 is not required
Term

Compare NADH and FADH with respect to: (1) Mechanism of accepting or donating electrons, (2) Affinity for the apoenzyme, (3) reactivity in solution, and (4) ability to act as a feedback inhibitor or activator

Definition

FAD accepts a single electron, NAD accepts a pair

FAD stays tightly bound to an enzyme, nad acts like a substrate

FAD is more reactive

NAD can have a regulatory role FAD stays bound and cannot.

Term
What is the purpose of the thioester bond in acetyl CoA and succinyl CoA?
Definition

activation of 2 carbons in the acetylCoA thioester.

Formation of a high energy bond.

Term

Name the five cofactors of the a-ketoglutarate dehydrogenase reaction. Name the vitamins from which four of them are derived! What is the advantage of a multienzyme complex?

Definition

thiamine pyrophosphate/thiamine

lipoate/none

FAD/

dihydrolipoyl dehydrogenase/

Efficients transfer without energy loss

Term

Several enzyme reactions in the TCA cycle are considered irreversible. Why?

Definition

large negative values for delta G o'

The concentrations never get high enough physiologically to push the reactions backwards

Term

Given the delta-G0! for each enzymatic step in a sequence of enzymatic reactions, be able to state the delta-G0! for the overall reaction.

Definition

add them up

Term

How is the rate of the TCA cycle linked to muscle contraction and the utilization of ATP?

Definition

through the ATP/ADP ratio

Term
Name two control enzymes of the TCA cycle
Definition

citrate synthase is regulated by its product

malate dehydrogenase is regulated by nadh

Term
Name four dietary sources of acetyl CoA!
Definition

vinegar

ethanol

sugar

fatty acids

Term
Which enzyme reaction in the TCA cycle is similar to the pyruvate dehydrogenase reaction? How could this relationship come about?
Definition

alpha ketoglutarate dehydrogenase

through a common ancestor

Term
Why are the symptoms for pyruvate dehydrogenase complex deficiency so apparent in the central nervous system and not in most other tissues?
Definition
Because nervous tissues derive their energy fro the oxidation of glucose to CO2
Term
Explain how the rate of the pyruvate dehydrogenase complex is related to the rate of utilization of ATP.
Definition

[image]

Term
Name five pathways which use TCA cycle intermediates as substrates. What is the effect of these pathways on the TCA cycle?
Definition
[image]
Term
If TCA cycle intermediates are constantly being removed for biosynthesis, why doesn't the cycle stop?
Definition
anaplerotic reactiosn constatly fill up the cycle
Term

Be able to fully describe the anaplerotic reaction that links glycolysis and the TCA cycle. Name the enzyme, substrate, product, biological compartment and tissues of interest. Name the regulatory factor (activator) and explain how the system regulates the production of the TCA cycle intermediate. What coenzyme is used in the reaction?

Definition
[image]
Term

Why are the symptoms for pyruvate carboxylase deficiency so apparent in the central nervous system and not in most other tissues?

Definition
it is essential to the formation of glutamine
Term

In addition to pyruvate, name two other classes of compounds that can be used to as substrates for anaplerotic reactions.

Definition
amino acids and CO2
Term
 Concerning Otto Shape, can succinate be oxidized without oxygen being consumed?
Definition
Yes
Term

Concerning Otto Shape, explain the effect of increased muscle contraction upon the concentrations of ATP, ADP, AMP, NADH, FAD(2H), and Acetyl Co A. What effect does this have upon the rate of the TCA cycle and the pyruvate dehydrogenase reaction?

Definition
usage of ATP decreases ADP AMP NADH FAD2H and Acetyl CoA.  Hence the TCA cycle speeds up to meet demand
Term

Concerning Otto Shape, explain the effect of increased muscle contraction upon the concentrations of ATP, ADP, AMP, NADH, FAD(2H), and Acetyl Co A. What effect does this have upon the rate of the TCA cycle and the pyruvate dehydrogenase reaction?

Definition
Ca speeds up the TCA cycle and the PDC complex
Term

Concerning Otto Shape, explain the effect of increased muscle contraction upon the concentrations of ATP, ADP, AMP, NADH, FAD(2H), and Acetyl Co A. What effect does this have upon the rate of the TCA cycle and the pyruvate dehydrogenase reaction?

Definition

Be increasing vascular effiecieny thus allowing more O2 to reach the working muscles

Term

Concerning a patient who suffers from anorexia nervosa and may have developed subclinical deficiencies of many vitamins, which vitamins would you prescribe to be positive that the pyruvate dehydrogenase and the pyruvate carboxylase reactions would have an adequate amount of cofactors?

Definition

biotin

Term
Concerning Al Martini who is an alcoholic, why does he have a thiamine deficiency?
Definition

ethanol consumption interferes with thiamine absorption

Term

Concerning Al Martini: Given that a-ketoacids build up in the heart in wet beriberi, develop a scenario that would explain why peripheral vessels dilate and cardiac muscles loose their contractility.

Definition

perhaps a change in osmotic gradients due to the ketoacids all stay near the heart?  Thiamine injections resolve the issue.

Term
Be able to draw a cartoon demonstrating oxidative phosphorylation. Include NADH, complexes I, II, III and IV, CoQ, cytochrome c, and ATP synthase. Demonstrate the sites for the pumping of protons and the direction of movement. Indicate the excess protons on one side of the membrane. Draw equations showing the synthesis of H2O and ATP.
Definition

[image]

Term
Why does the movement of protons produce ATP?
Definition

Because they are linked by the ATP synthase enzyme

Term

Where is complex II found? What reaction of the TCA cycle does it catalyze? How much ATP is produced when 2 electrons of succinate are passed through the chain to O2? Which complexes couple proton pumping and succinate oxidation?

Definition

In the intermembrane/matrix membrane.  The reoxidation of NADH. 

-7Kcal 

Succinate dehydrogenase.

Term

What is the function of an electron in the electron transport chain?

Definition

to power the movemet of protons against their concentration gradient

Term

What is a cytochrome?

Definition

a heme group associated with a protien

Term

Explain how iron deficiency anemia affects oxygen transport in the blood and oxidative phosphorylation in mitochondria.

Definition

It causes fatigue by not providing enough heme groups for the electron transport chain.

Term
What reaction is catalyzed by cytochrome oxidase?
Definition
transfer of electrons from cytochrome c to cytochrome aa
Term
Be able to state the chemiosmotic theory!
Definition
energy for ATP synthesis is produced by an electrochemical gradient across the inner mitochondrial membrane.
Term

How many ATPs are synthesized by ATP synthase for each NADH oxidized by the electron transport chain? How many for FAD(2H)?

Definition

NAD = 3 ATP

 

FAD = 2 ATP

Term
Is oxidative phosphorylation a reversible reaction? Why?
Definition

Yes if there is a lack of oxygan it will run backwards.

Term

What portion of the ETC is inhibited by CN-? What is the effect of cyanide inhibition upon proton pumping and ATP synthesis?

Definition

The heme portion of cytochrome aa in cytochrome c oxidase.  It stops electron transport

Term

Why does an impairment of the electron transport chain result in lactic acidosis?

Definition

It impairs oxidation of fatty acids

pyruvate builds up

excess pyruvate is converted to lactate

Term
How does shivering generate heat?
Definition
by burning ATP and running the electron transport chain.  ETC gives off a lot of heat.
Term
Be able to go through the series of events whereby increases ATP utilization is coupled to increased O2 utilization.
Definition
decreased ATP leads to a build up of ADP which will almost pull the reaction forward.  Not to mention all the feed back mechanisism of the TCA cycle.
Term
Be able to go through the series of events whereby pyruvate dehydrogenase is activated by increased ATP utilization.
Definition
Term

Understand how a chemical uncoupler works. What happens to heat production, proton pumping, ATP synthesis, and NADH utilization following uncoupling?

Definition

An uncoupler allows protons to leak back across from the cytosol to the matrix space.  This decreases the proton gradient and slows production of ATP

Term

What is the difference between an inhibitor of electron transport and an uncoupler of electron transport with respect to NADH utilization, proton pumping, and ATP synthase

Definition

Uncouplers disengage the clutch

Inhibitors like Cyanide stop the engine.

Term
Give an example of both a symport and an antiport that functions in the mitochondrial membrane
Definition

Symport= phosphate transporter translocate two molecules of different charge

 

antiport = ANT trasports one molecule for another of similar charge.  works by have the same charge but less of it thus powered by the proton gradient.

Term

Concerning Cora Nari: She had a heart attack. Why was nasal oxygen administered? Why was her blood pressure lowered? What might have been the effect on ATP production if nitroprusside had been continued for several days?

Definition

To supply oxygen to the blocked tissues.

To reduce demand on the heart?

It would convert to cyanide and stop the electron transport chain

Term

Concerning Cora Nari: What is TPA and how does it dissolve blood clots?

Definition

A recombinant tissue plasminogen activator.  it stimulates conversion of plasminogen back to plasmin

Term

Concerning Cora Nari: How did the change in the ratio of ATP to ADP and AMP affect anaerobic glycolysis? How did this affect the pH?

Definition

Anaerobic glycolysis picks up to generate some energy in the abscence of oxygen.  This creates lactic acid and lowers Ph

Term

Concerning X.S.Teefore, Explain how the affect of excess thyroid hormone on oxidative phosphorylation could explain increased appetite and sweating?

Definition

The electron transport chain is running to fast thus increasing the need for fuel and creating excess heat.

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