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Biochemistry > Citric Acid Cycle > Flashcards

Citric Acid Cycle Flashcards

1
Q

What stage of cellular respiration is the citric acid cycle

A

Stage 2

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2
Q

Where does CAC take place

A

In the mitochondria

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3
Q

What is the word description of the Tricarboxcylic acid cycle?

A

acetyl groups enter the citric acid cycle, which enzymatically oxidizes them to CO2.

The energy released by oxidation is conserved in the reduced electron carriers NADH and FADH2.

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4
Q

Why is CAC known as the final common pathway for the aerobic respiration of macronutrients?

A

carbohydrate, lipid, and protein which are broken down into glucose, fatty acids, and most amino acids are metabolized to acetyl- CoA or intermediates of the cycle.

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5
Q

Why is the citric acid cycle important?

A

produces important precurors that form building blocks of many other molecules.

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6
Q

What molecules can be converted into Acetyl CoA?

A

Ketogenic AA
Ketone bodies
Pyruvate
FA

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7
Q

How is pyruvate from glycolysis transported to the CAC?

A

pyruvate/H+ symport in the inner mitochondrial membrane

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8
Q

Does pyruvate/H+ symport require energy to function?

A

Yes, stored energy is coming from IMM where there is an electrical potential gradiet

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9
Q

Where does the first reaction take place

A

In the mito of eukaryotes and the cystosol of prokaryotes

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10
Q

What enzyme catalysed the conversion of pyruvate to Acetyl CoA?

A

pyruvate dehydrogenase (PDH) complex,

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11
Q

What 3 distinct enzymes make up PDH complex

A

pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (E2), and dihydrolipoamide dehydrogenase (E3).

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12
Q

Which 5 coenzymes are required for PDH complex to function?

A

thiamine pyrophosphate (TPP)

Flavin adenine dinucleotide (FAD)

CoA

nicotinamide adenine dinucleotide (NAD) lipoate

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13
Q

Which enzyme does TPP bind to?

A

active site of E1 pyruvate dehydrogenase

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14
Q

Which coenzyme bind to of E2?

A

dihydrolipoamide acetyltransferase (E2) binds to lipoate

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15
Q

Which Enzyme does FAD bind to?

A

flavin adenine dinucleotide binds to E3

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16
Q

What happens in E1

A

In the first step, E1 (pyruvate dehydrogenase) catalyzes oxidative decarboxylation of pyruvate. One carbon atom is removed from pyruvate as CO2.
The resulting 2-carbon molecule, hydroethyl is bound to TPP.

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17
Q

What happens in E2?

A

E2 (dihydrolipoamide acetyltransferase), which transfers the hydroethyl group from TPP to the oxidized form of lipoamide.
The acetyl group is then transferred to free coenzyme A to form acetyl-CoA and reduced lipoamide.

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18
Q

What happens in E3

A

FAD-dependent E3 (dihydrolipoamide dehydrogenase) reoxidizes the lipoyl group E2. The electrons are accepted by FAD to form FADH2,
which is then donated to NAD+ to form NADH

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19
Q

Which Enzymes complexes are needed to form Acetyl CoA?

A

E1 – Pyruvate dehydrogenase
E2 – Dihydrolipoamide acetyltransferase
E3 – Dihydrolipoamide dehydrogenase

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20
Q

Which enzyme catalyses the overall reaction of the formation of Acetyl CoA?

A

Pyruvate dehydrogenase

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21
Q

Is the formation of acetyl CoA reversible?

A

No it is irreversible

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22
Q

What kind of reaction is the formation acetyl CoA?

A

Oxidative decarboxylation in which the carboxyl group is removed from pyruvate as a molecule of CO2 and the two remaining carbons become the acetyl group of acetyl-CoA.

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23
Q

What does thiamine deficiency cause?

A

CNS problems is because brain cells are unable to produce sufficient ATP (via the TCA cycle) if the PDH complex is inactive.

Beriberi, characterized by loss of neural function.

Wernicke-Korsakoff, an encephalopathy-psychosis syndrome due to thiamine deficiency, may be seen with alcohol abuse.

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24
Q

Which B vitamin is thiamine?

A

B1

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25
Q

What serves as an indicator for defects in pyruvate oxidation?

A

elevated level of pyruvate in the blood

26
Q

What causes the activation of PDH complex

A

The accumulation of AMP, CoA, and NAD+ causes activation allosterically

27
Q

Which protein phosphorylates and inhibits PDH Complex?

A

PDH kinase

28
Q

What activates PDH Kinase

A

ATP, acetyl-CoA and NADH.

29
Q

What inhibits PDH complex?

A

pyruvate

30
Q

Which enzyme activates E1 by removing the phosphorylation group by hydrolysis?

A

PDH phosphatase

31
Q

Which mineral strongly activates PDH phosphatase?

A

Calcium

32
Q

What is the most common cause of congenital lactic acidosis.

A

deficiency in the E1 component of the PDH complex

33
Q

What is the significance of Pyruvate dehydrogenase deficiency?

A

causes problems for the brain, which relies on the TCA cycle for most of its energy and is particularly sensitive to acidosis.

34
Q

What are the symptoms of Pyruvate dehydrogenase deficiency?

A

neurodegeneration, muscle spasticity and, in the neonatal onset form, early death.

35
Q

Which enzyme complex defect affects both males and females and is classified as X- linked dominant?

A

E1: pyruvate dehydrogenase

36
Q

What treatment can be done for PDH deficiency

A

dietary restriction of carbohydrate and supplementation with TPP may

37
Q

What is the first reaction of CAC

A
38
Q

What is the first reaction of CAC

A
  1. the condensation of acetyl-CoA with oxaloacetate to form citrate, catalyzed by citrate synthase
39
Q

What is the second reaction of CAC

A

2.
Formation of Isocitrate via cis-Aconitate: Citrate is isomerized to isocitrate by the enzyme aconitase.

40
Q

What inhibits the TCA cycle? How?

A

Fluoroacetate

first converted to fluorocitrate by citrate synthase.
• Fluorocitrate is a potent inhibitor of aconitase.

41
Q

What inhibits TCA cycle?

A

Fluoroacetate

first converted to fluorocitrate by citrate synthase.
• Fluorocitrate is a potent inhibitor of aconitase.

42
Q

What inhibits the TCA cycle?

A

Fluoroacetate
• Fluoroacetate is first converted to fluorocitrate by citrate synthase.
• Fluorocitrate is a potent inhibitor of aconitase.

43
Q

Source of Fluoroacetate?

A

A range of plant species

Some flourinated compounds such as in anticancer agents, pesticides, and industrial chemicals can
be metabolized to fluoroacetate.

44
Q

What is the 3rd reaction of TCA Cycle?

A
  1. Oxidation of Isocitrate to α-Ketoglutarate and CO2:
    isocitrate dehydrogenase catalyzes oxidative decarboxylation of isocitrate to form α-ketoglutarate and CO2
45
Q

Which is the first rate limiting step

A

Reaction 3

46
Q

What and how is Isocitrate dehydrogenase activated?

A

Isocitrate dehydrogenase is allosterically activated by ADP and Ca2+

47
Q

What inhibits isocitrate dehydrogenase?

A

ATP and NADH.

48
Q

What is the 4th reaction in TCA

A

oxidative decarboxylation, in which α-ketoglutarate is converted to succinyl-CoA and CO2 by the action of the α-ketoglutarate dehydrogenase complex.

49
Q

What cofactors/enzymes are needed for reaction 4 to take place?

A

TPP, lipoid acid, CoASH, FAD and NAD+

50
Q

Why are those specific cofactors/enzymes needed for reaction 4 to take place?

A

•α-Ketoglutarate dehydrogenase is nearly identical to PDH in terms of reactions catalysed and its structural features

51
Q

What inhibits α-Ketoglutarate dehydrogenase complex ?

A

its products, NADH and succinyl CoA,

52
Q

What activates α-Ketoglutarate dehydrogenase complex?

A

Ca2+

53
Q

What is the fifth reaction in TCA

A

Succinyl-CoA is cleaved by Succinyl-CoA synthetase to form Succinate and GTP

reaction is coupled to phosphorylation of guanosine diphosphate (GDP) to guanosine triphosphate (GTP

54
Q

What is GTP used for?

A

mitochondrial synthesis of proteins, RNA and DNA.

55
Q

What is the other fate of GPT?

A

GTP formed can donate its phosphoryl group to ADP to form ATP, in a reversible reaction catalyzed by nucleoside diphosphate kinase.

56
Q

What is the 6th TCA cycle reaction?

A

Oxidation of Succinate to Fumarate: The succinate is oxidized to fumarate by the flavoprotein succinate dehydrogenase:

57
Q

Which enzyme is the only one that is membrane bound in the TCA in eukaryotes

A

succinate dehydrogenase is tightly bound to the inner mitochondrial membrane

58
Q

What activates Succinate dehydrogenase?

A

ATP and succinate

59
Q

What inhibits Succinate dehydrogenase?

A

Malonate (analog of succinate)

oxaloacetate

60
Q

What is the 7th reaction in the sequence?

A

The reversible hydration of fumarate to L-malate is catalyzed by fumarase

OH and H are used together with the enzyme fumarase to form Malate

61
Q

What is the 8th and final reaction of the TCA cycle?

A

NAD+-linked L-malate dehydrogenase catalyzes the oxidation of L- malate to oxaloacetate:

Biochemistry (6 decks)

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