01b: PDH, TCA Cycle, Urea Cycle

Question 1

Overall PDH rxn: what goes in?

Answer 1

Pyruvate, NAD, CoA

Question 2

Overall PDH rxn: what comes out?

Answer 2

Acetyl-CoA, CO2, NADH

Question 3

PDH: (oxidation/reduction) must occur to produce acetyl-CoA. Otherwise, (carboxylation/decarboxylation) will produce a(n) (X).

Answer 3

Oxidation (thus, NAD reduction);
Decarboxylation;
X = acetyladehyde

Question 4

Dehydrogenation is essentially (oxidation/reduction)

Answer 4

Oxidation

Question 5

List the three components of PDH and their cofactors.

Answer 5

1. PDH (ft. TPP)
2. Dihydrolipoyl transacetylase (ft. Lipoic acid)
3. Dihydrolipoyl dehydrogenase (ft. FAD)

Question 6

Vit B1 is (X), B2 is (Y). Which cofactor is each important for?

Answer 6

X = thiamine (TPP)
Y = riboflavin (FAD)

Question 7

Lipoic acid is cofactor for (X) of PDH complex. It attaches to (Y) residue of (X).

Answer 7

X = Dihydrolipoyl transacetylase;
Y = lysine

Question 8

E3 of PDH complex is important for regenerating (lipoic/dihydrolipoic) acid from (lipoic/dihydrolipoic) acid. Star the reduced form of the compound and state whether this reaction is an oxidation or reduction.

Answer 8

Lipoic;
Dihydrolipoic*

(Thus, this is an oxidation reaction)

Question 9

E3 has to (oxidize/reduce) (X) to regenerate (lipoic/dihydrolipoic) acid.

Answer 9

Reduce;
X = FAD
Lipoic

Question 10

(X) component of PDH (oxidizes/reduces) (FAD/FADH2) via (oxidation/reduction) of (NAD/NADH).

Answer 10

X = E3 (dihydrolipoyl dehydrogenase);
Oxidizes FADH2 (back to FAD);
Reduction of NAD

Question 11

T/F: Acetyl-CoA cannot be converted back to glucose.

Answer 11

True (hence importance of PDH regulation)

Question 12

High values for which ratios inhibit PDH?

Answer 12

1. Acetyl-CoA:CoA

2. NADH:NAD

Question 13

High values for which ratios activate PDH kinase, thus (activating/inhibiting) PDH?

Answer 13

Inhibiting;

1. Acetyl-CoA:CoA
2. NADH:NAD
3. ATP/ADP

Question 14

PDH Phosphatase is activated by (X), which then are indirect (stimulators/inhibitors) for PDH.

Answer 14

Stimulators;

X = Insulin, Pyruvate, Ca

Question 15

How would you expect PDH deficiency to impact lactate levels? Pyruvate?

Answer 15

Both elevated

Question 16

PDH deficiency is commonly inherited/transmitted in (X) manner. It may result in death of newborn due to severe (Y)

Answer 16

X = X-linked
Y = lactic acidosis

Question 17

The fundamental issue in PDH deficiency is one of (synthesis/degradation/transport).

Answer 17

Transport of E1a into mitochondria

Question 18

TCA Cycle (uses/produces) (X) molecules of CO2 per cycle.

Answer 18

Produces;

X = 2

Question 19

TCA Cycle produces (X) NADH and (Y) FADH2 and (Z) ATP.

Answer 19

X = 3
Y = 1
No ATP, but 1 GTP

Question 20

Production of (X) in TCA Cycle is example of substrate level phosphorylation.

Answer 20

X = GTP

Question 21

(X) component of TCA Cycle can branch off and become Phosphoenolpyruvate, which can enter (Y) reaction.

Answer 21

X = oxaloacetate;
Y = gluconeogenesis

Question 22

FA synthesis can occur when (X) component of TCA Cycle becomes (Y) compound.

Answer 22

X = citrate (exits to cytoplasm);
Y = acetyl-coa (by releasing oxaloacetate FYI)

Question 23

(X) enzyme of TCA Cycle is similar to PDH in structure/cofactors, but differs in which regulation mechanism?

Answer 23

X = alpha-ketoglutarate dehydrogenase;

Not regulated by phosphorylation

Question 24

List the enzymes in TCA cycle that carry out reduction of NAD.

Answer 24

1. Isocitrate dehydrogenase
2. Alpha-ketoglutarate dehydrogenase
3. Malate dehydrogenase

Question 25

Succinyl-CoA inhibits (X) enzyme of TCA Cycle.

Answer 25

X = Alpha-ketoglutarate dehydrogenase

Question 26

Arsenic poisoning is a reaction with (X), which (stimulates/inhibits) (Y) key enzymes.

Answer 26

X = lipoic acid Inhibits; Y = PDH and Alpha-ketoglutarate dehydrogenase

Question 27

Isocitrate dehydrogenase enzymes differ in their (oxidation/reduction) of (X).

Answer 27

Reduction; | X = NAD or NADP

Question 28

Mutations in (X) isozymes of isocitrate dehydrogenase result in (loss/gain) of function.

Answer 28

X = IDH1 or IDH2 | Gain (oncogenic mutations)

Question 29

Two major systems for degrading proteins are:

Answer 29

1. Lysosomes | 2. Ubiquitin-proteosome

Question 30

The toxic byproduct of AA metabolism is (X). (Y) organ takes care of this by converting it to (Z).

Answer 30

``` X = Free ammonia Y = liver Z = non-toxic urea ```

Question 31

List the enzymes of the urea cycle in order of action. Star the ones in the cytosol. Where are the others?

Answer 31

1. Carbamoyl-P Synthetase 2. Ornithine transcarbamoylase 3. Argininosuccinate synthetase* 4. Argininosuccinase* 5. Arginase* Mitochondrial matrix

Question 32

In urea cycle, (X) is transported out of mito in exchange for (Y) coming in.

Answer 32

``` X = citrulline Y = ornithine ```

Question 33

The importance for compartmentation of (X) enzymes in urea cycle is that (Y) is also an intermediate for (Z) pathway.

Answer 33

``` X = Carbamoyl-P synthetase and ornithine transcarbamoylase Y = carbamoyl-P Z = pyrimidine biosynthesis (in cytoplasm) ```

Question 34

The two forms of (X) enzyme are important control points for urea cycle and pyrimidine biosynthesis. Which reaction/enzyme is compartmentalized in mito?

Answer 34

X = carbamoyl-P synthetase (1 and 2) Carbamoyl-P synthetase 1 (for urea cycle)

Question 35

A total of (X) ATP are (produced/used) by one round of urea cycle. How many ADP/AMP are (used/produced)

Answer 35

X = 3 2 ADP, 1 AMP produced

Question 36

Big picture: what are the components that go into urea cycle?

Answer 36

CO2, NH4, 3 ATP, Asp, 2 H2O

Question 37

Big picture: what are the products of the urea cycle?

Answer 37

Urea, 2 ADP, 2 Pi, AMP, PPi, fumarate

Question 38

(Asp/fumarate) is needed for the urea cycle. Then, (X) enzyme produces (asp/fumarate) when (Y) is produced.

Answer 38

Asp; X = argininosuccinase Fumarate Y = arginine

Question 39

TCA Cycle enzymes are important for urea cycle in conversion/recycling of (X) to (Y).

Answer 39

``` X = fumarate Y = aspartate ```

Question 40

Excess nitrogen from the metabolism of amino acids in muscle is largely transferred to the liver in the form of:

Answer 40

Alanine