TCA Cycle (midterm) Flashcards

1
Q

Only 10% of the energy contained in the glucose molecule is extracted by glycolysis. So approx 90% of the biologically available energy in the molecule remains in ____________

A

pyruvate

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1
Q

The TCA cycle oxidizes acetyl CoA to….

A

CO2 and H2O

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2
Q

The TCA cycle generates _______ ATP per pyruvate or ______ ATP per acetyl Co-A

A

15, 12

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3
Q

What enzyme is used to convert pyruvate into acetyl CoA? What is this reaction called?

A

pyruvate dehydrogenase (PDH)

Oxidative decarboxylation rxn

this rxn is known as pyruvate oxidation

it forms a CoA thioester

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4
Q

Where is PDH located?

A

in the mitochondria

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5
Q

What 5 coenzymes are required to convert pyruvate to acetyl CoA?

A

1) thiamine pyrophosphate
2) lipoate
3) CoA
4) FAD
5) NAD+

mnemonic: Tender loving care for Nancy

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6
Q

What is the only irreversible step in the human body?

A

pyruvate to acetyl CoA

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7
Q

What effect does alcohol have on glucose metabolism?

A

-chronic alcoholics tend to be hypoglycemic and suffer from lactoacidosis (bc pyruvate can only convert to lactate in this case)
-chronic alcoholics frequently have a thiamine deficiency, which leads to a non-functional PDH
-infusing glucose and thiamine corrects the hypoglycemia
-the intermediate acetaldehyde is extremely toxic

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8
Q

What 4 enzymes require these 5 coenzymes:
1) thiamine pyrophosphate
2) lipoate
3) CoA
4) FAD
5) NAD+
(Tender loving care for Nancy)

A

1) PDH
2) alpha KG DH (from TCA)
3) branch chain ketoacid DH (in the catabolism of branched chain AA) (if this is deficient= maple syrup urine disease)

those 3 enzymes are all located in mitochondrial matrix

4) transketolase (catalyzes the rxn of ribose 5 phosphate to other sugars in the PPP pathway and is located in the cytoplasm)

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9
Q

What are the other names for TCA cycle?

A

-cyclic acid cycle
-citric acid cycle
-citrate cycle
-krebs cycle

its called this bc citrate has 3 carboxyl groups

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10
Q

What is the substrate for the TCA cycle?

A

acetyl CoA

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11
Q

How many carbons is in acetyl CoA?

A

2C

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12
Q

In the TCA cycle, acetyl CoA undergoes a reaction with what enzyme to make citrate? What vitamin is required here?

A

citrate synthase

vitamin required is vit B5

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13
Q

How many carbons is citrate?

A

6C

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14
Q

In the TCA cycle, citrate undergoes a reaction with what enzyme to make isocitrate?

A

aconitase

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15
Q

How many carbons is isocitrate?

A

6C

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16
Q

In the TCA cycle, isocitrate undergoes an oxidative decarboxylation reaction with what enzyme to make alpha KG? What else is made here?

A

isocitrate DH (IDH)

NADH was made and released along with CO2

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17
Q

How many carbons is alpha KG?

A

5C

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18
Q

In the TCA cycle, alpha KG undergoes an oxidative decarboxylation reaction with what enzyme to make succinyl-CoA, NADH, and CO2? What does this enzyme require?

A

alpha KG DH

requires TLCFN coenzymes

note: NADH and CO2 was released

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19
Q

How many carbons is succinyl-CoA?

A

4C

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20
Q

In the TCA cycle, succinyl-CoA undergoes substrate level phosphorylation with what enzyme to make GTP and succinate?

A

succinyl-CoA synthetase or succinate thiokinase

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21
Q

How many carbons is succinate?

A

4C

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22
Q

In the TCA cycle, succinate undergoes a reaction with what enzyme to make fumarate and FADH2?

A

succinate DH (SDH)

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23
Q

Where is SDH located?

A

in the inner mitochondrial membrane

SDH is a part of TCA and ETC

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24
Q

How many carbons is fumarate?

A

4C

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25
Q

In the TCA cycle, fumarate undergoes a hydration reaction with what enzyme to make malate?

A

fumarase

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26
Q

How many carbons is malate?

A

4C

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27
Q

In the TCA cycle, malate undergoes a reaction with what enzyme to make OAA and NADH?

A

malate DH

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28
Q

How many carbons is OAA?

A

4C

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29
Q

In the TCA cycle, do we create OAA?

A

no its recycled

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30
Q

What is the net yield from acetyl CoA?

A

-2 CO2

-3 NADH are used to make 9 ATP
-1 FADH2 is used to make 2 ATP
-1 GTP
=total ATP is 12 (this is ONE TURN)

at this point 1 acetyl CoA is completely oxidized

note: the net yield for a molecule of pyruvate will be one more NADH which will make 15 ATP in total

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31
Q

Glycolysis generates 6 or 8 ATPs and 2 pyruvates. So, the net gain from the aerobic catabolism of glucose will be ______ ATPs

A

36/38 (this is with oxygen present and vitamin B1 present)

note: G > pyr> lactate makes 2 ATP per G, this is without oxygen and vitamin B1

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32
Q

Is any carbon dioxide produced in glycolysis? Where is carbon dioxide produced?

A

no, glycolysis only makes 2 ATP and 2 NADH in the cytoplasm

pyr to acetyl CoA makes 2 CO2 and 2 NADH in the mitochondria

TCA cycle makes 4 CO2 and 24 ATP with 2 turns

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33
Q

Acetyl CoA has 2C so it can make…

A

2 CO2 and 12 ATP

34
Q

pyruvate has 3C so it can make….

A

3 CO2 and 15 ATP

35
Q

glucose has 6C so it can make….

A

6 CO2 and 36-38 ATP

36
Q

When citrate levels are high, it wont go through TCA, instead it will convert to….

A

FAs and then fat or cholesterol

37
Q

When alpha KG levels are high, it will not continue through TCA. Instead it will be converted to….

A

AAs, most commonly glutamate

or can convert to purines

38
Q

When there are high levels of succinyl- CoA, it will not continue through TCA. Instead it will make….

A

heme

39
Q

Can malate change to glucose?

A

yes

40
Q

Where there are high levels of OAA, it can be converted to….

A

-AAs, most commonly aspartate
-glucose
-pyrimidines

41
Q

T/F: the TCA cycle is an amphibolic pathway

A

true

42
Q

When there are high levels of pyruvate, it can change to…

A

AAs or change back to glucose

43
Q

What hormone removed phosphate to activate PDH?

A

insulin (so glucagon does the opposite)

this is covalent modification

44
Q

What are the 5 allosteric activators for PDH?

A

increased:
-NAD+
-ADP
-CoA
-calcium
pyruvate

45
Q

What are the 3 allosteric inhibitors of PDH?

A

increased:
-acetyl CoA
-NADH
-ATP

46
Q

What is the major product of TCA cycle?

A

NADH because 3 NADH are created

47
Q

How is the TCA cycle regulated?

A

ALLOSTERIC REGULATION ONLY

there is no hormone/covalent modification with TCA

48
Q

T/F: the TCA cycle has NO diseases associated with it

A

true!!!

49
Q

What are the 3 RLEs in TCA cycle?

A

1) citrate synthase
2) isocitrate DH (IDH)
3) alpha KG DH

50
Q

What inhibits citrate synthase?

A

increased:
-NADH
-succinyl CoA
-citrate
-ATP

51
Q

What inhibits IDH?

A

increased ATP and/or NADH

52
Q

What inhibits alpha KG DH?

A

increased succinyl CoA and/or NADH

53
Q

What activates citrate synthase?

A

increased ADP

54
Q

What activates IDH?

A

increased ADP and/or calcium

55
Q

What activates alpha KG DH?

A

increased calcium

56
Q

What enzyme is the most regulated enzyme in TCA?

A

IDH

57
Q

If a person keeps eating but TCA shuts down because of enough ATP, then the ATP will be used to make glycogen, and if theres still enough then it would activate….

A

PFK1

58
Q

Is citrate a VIP molecule?

A

yes

59
Q

When is the citrate shuttle used?

A

When TCA cycle slows down and theres still extra glucose to be used up

its used for anabolic pathways, specifically for converting citrate to FA or cholesterol

60
Q

Where is the citrate shuttle located?

A

cytoplasm

61
Q

What is the difference between malate and citrate shuttle in terms of fed/fasting state?

A

citrate shuttle is used in fed state

malate shuttle is used in fasted state

62
Q

Citrate will get shuttled out of mitochondria when there is too much. It will break down into OAA and acetyl coa with which enzyme?

A

citrate lyase

63
Q

Citrate will get shuttled out of mitochondria when there is too much. It will break down into OAA and acetyl CoA with citrate lyase. The acetyl CoA will be used to make malonyl CoA, whereas the OAA gets converted to malate. Malate is also a VIP molecule and can either be shuttled back into mitochondria and convert back to OAA to go through TCA when its needed, or malate can be converted to pyruvate with the help of what enzyme?

A

malic enzyme (this also makes NADPH)

64
Q

Citrate will get shuttled out of mitochondria when there is too much. It will break down into OAA and acetyl CoA with citrate lyase. The acetyl CoA will be used to make malonyl CoA, whereas the OAA gets converted to malate. Malate is also a VIP molecule an can either be shuttled back into mitochondria and convert back to OAA to go through TCA when its needed, or malate can be converted to pyruvate with the help of malic enzyme (this also makes NADPH). Pyruvate is also a VIP and can be shuttled into mitochondria. Pyruvate can either convert to OAA or acetyl CoA depending on what is needed. What enzyme converts pyruvate to OAA?

A

pyruvate carboxylase

65
Q

Anaplerotic reactions restock the TCA cycle, it usually involves the synthesis of _____________ to shuttle out of mitochondria in a fasting state

A

OAA or malate

66
Q

Once malate moves out of the mitochondria, it never goes back because it will be used to make….

A

glucose (so after we’re fed, we have to restock TCA to make more malate)

67
Q

In the liver and kidneys, pyruvate is converted to OAA with what enzyme?

A

pyruvate carboxylase

68
Q

In the muscles, PEP is converted to OAA with what enzyme?

A

PEP CK

69
Q

In all tissues, pyruvate is converted to malate with what enzyme?

A

malic enzyme

70
Q

What enzymes are involved with pyruvate?

A

1) pyruvate kinase
2) pyruvate carboxylase
3) pyruvate DH
4) malic enzyme
5) lactate DH
6) PEPCK

71
Q

Why can’t we make glucose from FAs but plants can?

A

because plants have glyoxylate shunt and we do not

Plants can make glucose from acetyl CoA since they have a mechanism that bypasses the reactions of the TCA cycle that causes CO2 to be lost

72
Q

in plants, isocitrate gets broken down into glyoxylate and succinate with what enzyme?

A

isocitrate lyase

73
Q

in plants, isocitrate gets broken down into glyoxylate and succinate with isocitrate lyase. The succinate will be transported out to eventually make OAA. But the glyoxylate will undergo a reaction with what enzyme to make malate?

A

malate synthase (this also makes CoA)

the new malate that was created can be converted to glucose

74
Q

What enzymes do plants have that we do not?

A

isocitrate lyase and malate synthase

75
Q

What 2 enzymes in the TCA cycle make NADH and CO2?

A

IDH and alpha KG DH

(malate DH makes NADH but not CO2)

76
Q

What enzyme in TCA cycle can do substrate level phosphorylation?

A

succinyl CoA synthetase or succinate thiokinase

77
Q

How many NADH are created per glucose?

A

10 NADH

2 in glycolysis
2 from PO
3 from TCA (6 with 2 rounds)

78
Q

What enzymes make NADH in glycolysis?

A

GAP DH

79
Q

What enzyme makes NADH in pyruvate oxidation?

A

PDH

80
Q

How much ATP is made per glucose from glycolysis + TCA?

A

4 ATP

1 from phosphoglycerate kinase
1 from pyruvate kinase
2 GTP from succinate thiokinase (2 rounds)

81
Q

How much FADH2 is made per glucose?

A

2 FADH2 (with 2 rounds of TCA with SDH)

82
Q

What are the 5 VIP molecules we went over so far?

A

1) pyruvate
2) malate
3) citrate
4) aspartate
5) PEP

83
Q

Midterm warning= she has a lot of vitamin questions on midterm so if you don’t know/remember them go back to very first deck and review!

A