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Biochem block 2 > Lecture2-PYRUVATE METABOLISM&TCA CYCLE > Flashcards

Lecture2-PYRUVATE METABOLISM&TCA CYCLE Flashcards

1
Q

What is the primary role of mitochondria?

A

ATP production via aerobic respiration

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2
Q

Acetyl-coA is a common product in what?

A

catabolism of carbohydrates (glycolysis), amino acids and fatty acids (b-oxidation)

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3
Q

What type of pathway is the TCA cycle?

A

amphibolic pathway

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4
Q

What does it mean when the TCA cycle is amphibolic?

A

involving both catabolism (break down) and anabolism (synthesis) of molecules

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5
Q

What does it mean when the TCA cycle is amphibolic?

A

involving both catabolism (break down) and anabolism (synthesis) of molecules

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6
Q

What is the mitochondrial function?

A

-Tricarboxylic Acid Cycle
-beta-Oxidation of fatty acids
-Respiratory chain with ATP production through oxidative phosphorylation

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6
Q

What is the mitochondrial function?

A

-Tricarboxylic Acid Cycle
-beta-Oxidation of fatty acids
-Respiratory chain with ATP production through oxidative phosphorylation

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7
Q

what are the products of the TCA cycle?

A

NADH, FADH2 and GTP

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8
Q

What of the products of TCA cycle used for ?

A

used for ATP generation

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9
Q

what are the structures of the mitochondria?

A

outer membrane
inner membrane(cristae)
matrix

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10
Q

What is happening in the inner membrane (cristae)

A

oxidative phosphorylation

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11
Q

What is happening the matrix of the mitochondria?

A

PDH complex, TCA, Fatty acid B oxidation

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12
Q

Where is the PDH complex done?

A

matrix of the mitochondria

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13
Q

Where is the TCA cycle done?

A

Matrix of the mitochondria

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14
Q

Where does oxidative phosphorylation done?

A

Inner membrane of mitochondria

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15
Q

What are the metabolic fates of pyruvate?

A

Alanine (transmutation), oxaloacetate (Carboxylation), aceyl CoA(Oxidative decarboxylation) and Lactate (reduction)

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16
Q

Tell me about the pyruvate transport

A

A variety of different transport systems, such as symports and antiports, are present in the inner mitochondrial membrane

  • pyruvate transport has a pyruvate symport or shuttle that diffuses pyruvate(-) and H(+) through the inner mitochronial membrane . Since they are opposite charges they do not affect the electron gradient
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17
Q

What does the Pyruvate dehydrogenase complex do?

A

oxidative decarboxylation of pyruvate

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18
Q

What is the first step of the PDH complex?

A

Pyruvate to hydroxyethyl with pyruvate dehydrogenase

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19
Q

What allows the lipoid acid prosthetic group to rotate?

A

Lipoid acid is joined by an amide link to a lysine residue of the transacetylase component of the enzyme complex

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20
Q

What is the product of the Dihydrolipidyl transacetylase

A

Acetyle CoA

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21
Q

What is the product of the dihydrolipoyl dehydrogenase

A

NADH and H+

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22
Q

What are the products of the PDH complex?

A

NADH and H+
Acetyl CoA

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23
Q

How do you deactivate the PDH complex?

A

Active PDH Kinase through phosphorylation of PDH

(high ATP, high acetyl coA)

24
Q

How can you decrease the activity of pyruvate dehydrogenase (PDH) kinase?

A

Low ATP, Low acetyl CoA

25
Q

How you can increase the activity of pyruvate dehydrogenase (PDH) kinase) ?

A

HIGH ATP, HIGH acetyl Co-A

26
Q

How do you active the PDH Complex

A

dephosphrolation of PDH with pyruvate dehydrogenase phosphatase

27
Q

How do you increase the activity of pyruvate dehydrogenase phosphatase

A

Increase Mg, Insulin

28
Q

What are the sources of Acetyl CoA

A

Pyruvate, amino acids, fatty acids

29
Q

What are the fates of acetyl CoA

A

Tricarboxylic acid cycle, ketone bodies, sterols and fatty acids

30
Q

What are the fates of acetyl CoA

A

Tricarboxylic acid cycle, ketone bodies, sterols and fatty acids

31
Q

what are high energy molecules in the TCA cycle

A

acetyl coA, and succinyl CoA

32
Q

What three enzymes involve a lot of energy, exergonic?

A

Citrate synthase, isocitrate dehydrogenase and alpha ketaoglutarate dehydrogenase

33
Q

What is the rate limiting enzyme in TCA cyle

A

Isocitrate dehydrogenase
-isocitrate to a ketoglutaurate

34
Q

What is the first oxidation step in TCA cycle

A

NADH, H–> Isocitrate to oxalosuccinate with isocitrate dehydrogenase

Extra under oxalosuccinate: electron sink beta to carbon with COO to be removed

35
Q

What is the second oxidation in TCA?

A

NADH, H –> a-ketoglutrate aKG to succinyl CoA with a ketoglutarate dehydrogenase

C is converted to COs2

36
Q

What is the high energy molecule formed in TCA and what step?

A

GTP and succinyl CoA to succinate with succinyl CoA synthetase

37
Q

what is the 3rd oxidation in TCA

A

FAHH2 –>Succinate to fumarate with succinate dehydrogenase

38
Q

What the final oxidation in TCA?

A

NADH+H –> L-malate to oxaloacetate with malt dehydrogenase

39
Q

Where do you regulate the TCA cycle?

A

The 3 TCA cycle exergonic steps:
-Citrate synthase
-Isocitrate dehydrogenase (catalyzes rate-limiting step)
-a-Ketoglutarate dehydrogenase

40
Q

Where do you regulate the TCA cycle?

A

The 3 TCA cycle exergonic steps:
-Citrate synthase
-Isocitrate dehydrogenase (catalyzes rate-limiting step)
-a-Ketoglutarate dehydrogenase

41
Q

What inhibits the TCA cycle?

A

ATP, NADH, succinyl-CoA

42
Q

TCA is activated by what?

A

ADP and Ca++

43
Q

ADP and CA+ does what to the TCA cycle?

A

activate it

44
Q

What does ATP, NADH and succinyl-coA do to the TCA cycle?

A

inhibit it

45
Q

The pyruvate dehydrogenase complex is controlled by what?

A

allosteric and covalent mechanisms

46
Q

Oxaloactate from the TCA cycle goes where?

A

Amino acid synthesis

47
Q

Malate from the TCA cycle goes where?

A

gluconeogenesis

48
Q

succinyl coA from the TCA cycle goes where?

A

heme synthesis

49
Q

alpha ketoglutarate from the TCA cycle goes where?

A

Amino acid synthesis

50
Q

Citrate from the TCA cycle goes where?

A

fatty acid synthesis

51
Q

There is a metabolic problem with the TCA cycle, what is it?

A

to run TCA cycle you need not only acetyl-CoA but also oxaloacetate

52
Q

What is the solution of the metabolic problem of the TCA cycle?

A

Pyruvate carboxylase (+biotin) converts pyruvate to oxaloacetate

53
Q

What from the TCA can be toxic?

A

accumulation of the TCA cycle intermediates (succinate, fumarate) or TCA cycle substrates (pyruvate)

54
Q

an accumulation of TCA cycle intermediates (succinate, fumarate) or TCA cycle substrates (pyruvate) cause what?

A

particularly toxic to neurons and brain development (encephalopathies)

55
Q

What is Pyruvate dehydrogenase deficiency ?

A

-leading to chronic lactic acidosis (increased serum levels for lactate, pyruvate, alanine).

-Children with this disease frequently exhibit severe neurological defects; resulting in death in many cases

  • Dietary management may include ketogenic diet
56
Q

What is the management of pyruvate dehydrogenase deficiency?

A

ketogenic diet (high-fat, adequate- protein, low-carbohydrate diet) with minimal carbohydrates.

57
Q

What is fumarase deficiency?

A

-Rare autosomal recessive disease with severe neurological impairment.
-Urine contains abnormal amounts of fumarate and elevated levels of succinate and other TCA cycle intermediates.

Biochem block 2 (10 decks)

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