10: TCA Flashcards

1
Q

TCA cycle function

A

Oxidizes carbon fuels for harvesting high energy electrons

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2
Q

Is TCA catabolic or anabolic?

A

Amphibolic

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3
Q

Where does TCA take place?

A

Mito

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4
Q

Acetyl coA is the active form of what?

A

Acetate

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5
Q

What macromolecules can form acetyl CoA?

A

Carbs, lipids, and proteins

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6
Q

Two ways lipids can form acetyl CoA

A

TAGs -> FAs -> acetyl coA

Ketone bodies -> acetyl coA

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7
Q

Five PDC coenzymes and the vitamins they are derived from

A
TPP: B1
FAD: B2
NAD+: B3
CoA: B5
Lipoic acid: not from a vitamin
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8
Q

Where does phosphorylation occur on the PDC?

A

E1 complex, via TPP

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9
Q

What happens in a phosphatase deficiency?

A

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

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10
Q

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

A

Increases

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11
Q

Reducing power of a cell

A

NADH:NAD+ ratio

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12
Q

Two major things high citrate does

A
  1. Inhibits PFK-1 in glycolysis

2. Activates ACC in FA synthesis

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13
Q

What does high citrate indicate in a cell?

A

ATP-rich state

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14
Q

How does fluoroacetate work?

A

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

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15
Q

Two major anaplerotic reactions of TCA

A
  1. Degradation of AAs

2. Carboxylation of pyruvate

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16
Q

Degradation of AAs replenishes what four molecules in TCA?

A
  1. OAA
  2. a-ketoglutarate
  3. Succinyl CoA
  4. Fumarate
17
Q

Carboxylation of pyruvate replenishes what molecules in TCA?

A

OAA

18
Q

What cofactor does pyruvate carboxylase require?

A

Biotin

19
Q

Are lipids anaplerotic?

A

No, they are degraded exclusively to acetyl CoA

20
Q

Two classic TCA disorders and two recently discovered ones

A

Two classic: fumarase deficiency, 2-oxoglutaric aciduria

Two new: SCS deficiency, mitochondrial depletion syndrome

21
Q

Overview of the two classical TCA disorders

A

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

22
Q

How to diagnose the two classic TCA disorders?

A

Urinalysis

23
Q

Oncometabolites

A

Compounds that can be harmful if they build up

24
Q

Two oncometabolites of TCA

A
  1. Citrate

2. 2HG (2-hydroxyglutarate)

25
Q

PEP carboxykinase abormalities does what?

A

Promotes cancer cell growth

26
Q

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

A

Non-metastatic breast carcinoma

27
Q

Citrate as an oncometabolite

A
  1. Reduces PDC activity -> more glycolysis
  2. Increased pyruvate accumulation -> lactic acid -> cancer growth
  3. activates ACC -> lipid synthesis -> tumorigenesis
28
Q

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

A

Mutations in IDH1 and IDH2

29
Q

Precursor of 2-hydroxyglutarate

A

A-ketoglutarates

30
Q

What does excess 2HG lead to?

A

Gliomas