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Week 10-SHANE > PDH Complex and the CAC (TCA) > Flashcards

PDH Complex and the CAC (TCA) Flashcards

1
Q

What are the some of the sources of Acetyl CoA for the TCA cycle?

A
  • *1) glycolysis- conversion from pyruvate by pyruvate dehydrogenase
    2) oxidizing amino acids
    3) fatty acid B oxidation
    4) two carbons (like ethanol or acetate) and convert them
    5) ketone body metabolism
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2
Q

Where does the TCA cycle take place?

A

the mitochondrial matrix

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3
Q

How does pyruvate enter the mitochondria?

A

through porin molecules on the outer membrane (note that the inner membrane will not let pyruvate pass through- too tight)

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4
Q

How does pyruvate pass through the inner mitochondrial membrane?

A

through pyruvate carriers

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5
Q

Where does pyruvate dehydrogenase exist in the cell?

A

inside the mitochondrial matrix

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6
Q

What are the three enzyme activities of pyruvate dehydrogenase?

A

1) pyruvate decarboxylase (E1)
2) dihydrolipoyl transacetylase (E2)
3) dihydrolipoyl dehydrogenase (E3)

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7
Q

What is the function of the E1 domain of pyruvate dehydrogenase?

A

decarboxylates pyruvate

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8
Q

What is the function of the E2 domain of pyruvate dehydrogenase?

A

transfers acetyl group to CoA

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9
Q

What is the function of the E3 domain of pyruvate dehydrogenase?

A

reoxidizes dihydrolipoamide

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10
Q

What cofactor does E1 need in order to convert pyruvate to Acyl-TPP

A

thiamine pyrophosphate (TPP)

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11
Q

What cofactor does E2 need in order to convert Acyl-TPP to Acyl-lipoate?

A

lipoic acid with sulfur-sulfur bond

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12
Q

The term ‘dehydrogenase’ means taking off how many electrons?

A

2

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13
Q

What is the first step of the TCA cycle?

A

this is a condensation run

combine acetyl-CoA to oxalaoacetate (a 4-carbon dicarboxylic acid) to make citrate (a tricarboxylic acid)

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14
Q

What enzyme catalyzes the conversion of acetyl-CoA and oxaloacetate to citrate?

A

citrate synthase

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15
Q

How does citrate synthase work?

A

initially it gets oxaloacetate to bind to the protein which causes a change in structure and creates a new binding site for acetyl-CoA. The presence of both then causes another conformational change that stimulates conversion to citrate

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16
Q

What are the two fates of citrate?

A

1) continue through the TCA cycle
2) be exported to the cytosol to be reconverted to acetyl coA (and oxaloacetate) for fatty acid synthesis. Note that acetyl coA does not have a transporter in the mitochondria so it can only be recycled to the cytosol this way (conversion to acetyl-CoA and oxaloacetate happens by ATP-citrate-liase)

17
Q

What happens to citrate in the TCA cycle?

A

it is converted to isocitrate (through an intermediate- cis-Aconitate) by aconitase

18
Q

How does Aconitase work?

A

it shifts a central hydroxyl group to permit formation of an alpha-leto acid. This process works by removing water to make cis-aconitate and then re-adding water to make isocitrate (which has the hydroxyl group on a different carbon)

19
Q

What happens to isocitrate in the TCA cycle?

A

It is oxidized by isocitrate dehydrogenase to make a-ketogluterate (by giving off Co2 and making NADH)

20
Q

What are the fates of a-ketogluterate?

A

1) continue through TCA
2) use as a pre-cursor for amino acid synthesis (for glutamic acid, glutamine, proline etc).- only going to do this in an energy-rich situation

21
Q

What happens to a-ketogluterate in the TCA cycle?

What are the bi-products?

What enzyme?

A

it is converted to succinyl-coA by adding CoA-SH and through the enzyme a-ketogluterate dehydrogenase

Bi-products: Co2 and NADH

22
Q

How many carbons does succinyl-CoA have?

A

4

23
Q

What happens to succinyl-CoA in the TCA cycle?

What are the bi-products?

What enzyme?

A

it is converted to succinate by saucily CoA synthesase

Bi-porducts: CoA-SH, GTP (which is converted to ATP)

this reaction is reversible

24
Q

What happens to succinate in the TCA cycle?

What are the bi-products?

What enzyme?

A

it is converted to fumigate by succinate dehydrogenase

Bi-products: FAHD2

25
Q

What happens to fumerate in the TCA cycle?

What are the bi-products?

What enzyme?

A

It is converted to malate by fumarase (and through addition of water)

no bi-products

26
Q

What happens to malate in the TCA cycle?

What are the bi-products?

What enzyme?

A

it is converted to oxaloacetate by malate dehydrogenase

bi-product: NADH

27
Q

What is the only enzyme in the TCA cycle that is a membrane bound protein?

A

succinate dehydrogenase (has a FAD bound to it that allows binding of succinate)

28
Q

What AAs can oxaloacetate be used to make?

A

aspartic acid and asparagine

29
Q

What is succinyl-CoA a pre-cursor for?

A

it can leave the TCA and be a pre-cursor for porphyrins (for heme synthesis)

30
Q

How can oxaloacetate by replenished for the TCA?

A

conversion of pyruvate to oxaloacetate using pyruvate carboxylase (and ATP)

31
Q

What will activate conversion of pyruvate to oxaloacetate by pyruvate carboxylase?

A

high levels of acetyl CoA

32
Q

Using AAs to make intermediates of the TCA is called what?

A

anaplerotic rxns

33
Q

What are the main end-products of the TCA?

A

ATP and NADH (so high levels of either would inhibit the cycle)

34
Q

What steps of the TCA are regulated?

A

1) pyruvate to acetyl-CoA
2) Acetyl- CoA and oxaloacetate to citrate
3) isocitrate to a-ketogluterate
4) a-ketogluterate to succinyl-CoA

35
Q

Phosphorylation of what domain of pyruvate dehydrogenase will shut the enzyme down?

A

E1

36
Q

How is the glyoxylate cycle for bacteria different than the TCA?

A

once isocitrate is made, it is converted to succinate and glyoxylate by isocitrate lyase. The enzyme malate synthase will combine glyoxylate with acetyl-CoA to make malate which can be converted to oxaloacetate, which then can be used for gluconeogenesis (which humans can’t do).

The succinate that is made is put into the TCA cycle

37
Q

Review regulation of the TCA cycle

A

Review regulation of the TCA cycle

Week 10-SHANE (17 decks)

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