10: TCA

Question 1

TCA cycle function

Answer 1

Oxidizes carbon fuels for harvesting high energy electrons

Question 2

Is TCA catabolic or anabolic?

Answer 2

Amphibolic

Question 3

Where does TCA take place?

Answer 3

Mito

Question 4

Acetyl coA is the active form of what?

Answer 4

Acetate

Question 5

What macromolecules can form acetyl CoA?

Answer 5

Carbs, lipids, and proteins

Question 6

Two ways lipids can form acetyl CoA

Answer 6

TAGs -> FAs -> acetyl coA

Ketone bodies -> acetyl coA

Question 7

Five PDC coenzymes and the vitamins they are derived from

Answer 7

TPP: B1
FAD: B2
NAD+: B3
CoA: B5
Lipoic acid: not from a vitamin

Question 8

Where does phosphorylation occur on the PDC?

Answer 8

E1 complex, via TPP

Question 9

What happens in a phosphatase deficiency?

Answer 9

PDC always inactive -> glucose goes to lactate -> lactic acidosis -> affects CNS

Question 10

What does TCA do when there’s low cellular ATP?

Answer 10

Increases

Question 11

Reducing power of a cell

Answer 11

NADH:NAD+ ratio

Question 12

Two major things high citrate does

Answer 12

1. Inhibits PFK-1 in glycolysis

2. Activates ACC in FA synthesis

Question 13

What does high citrate indicate in a cell?

Answer 13

ATP-rich state

Question 14

How does fluoroacetate work?

Answer 14

Reacts with CoA -> fluoroacetyl CoA -> competitive inhibitor of aconitase -> inhibited aconitase leads to citrate buildup -> inhibits citrate synthase

Question 15

Two major anaplerotic reactions of TCA

Answer 15

1. Degradation of AAs

2. Carboxylation of pyruvate

Question 16

Degradation of AAs replenishes what four molecules in TCA?

Answer 16

1. OAA
2. a-ketoglutarate
3. Succinyl CoA
4. Fumarate

Question 17

Carboxylation of pyruvate replenishes what molecules in TCA?

Answer 17

OAA

Question 18

What cofactor does pyruvate carboxylase require?

Answer 18

Biotin

Question 19

Are lipids anaplerotic?

Answer 19

No, they are degraded exclusively to acetyl CoA

Question 20

Two classic TCA disorders and two recently discovered ones

Answer 20

Two classic: fumarase deficiency, 2-oxoglutaric aciduria

Two new: SCS deficiency, mitochondrial depletion syndrome

Question 21

Overview of the two classical TCA disorders

Answer 21

Rare disorders with global developmental delays and severe neurological issues, with variable severity and typically lethal in first ten years of life

Question 22

How to diagnose the two classic TCA disorders?

Answer 22

Urinalysis

Question 23

Oncometabolites

Answer 23

Compounds that can be harmful if they build up

Question 24

Two oncometabolites of TCA

Answer 24

1. Citrate

2. 2HG (2-hydroxyglutarate)

Question 25

PEP carboxykinase abormalities does what?

Answer 25

Promotes cancer cell growth

Question 26

What type of cancer has been found linked to TCA dysfunctions?

Answer 26

Non-metastatic breast carcinoma

Question 27

Citrate as an oncometabolite

Answer 27

1. Reduces PDC activity -> more glycolysis 2. Increased pyruvate accumulation -> lactic acid -> cancer growth 3. activates ACC -> lipid synthesis -> tumorigenesis

Question 28

What mutations cause accumulation of 2HG (2-hydroxyglutarate)?

Answer 28

Mutations in IDH1 and IDH2

Question 29

Precursor of 2-hydroxyglutarate

Answer 29

A-ketoglutarates

Question 30

What does excess 2HG lead to?

Answer 30

Gliomas