Chapter 19 = TCA cycle Flashcards

1
Q

What does the TCA cycle stand for?

A

TCA cycle = Tricarboxylic Acid Cycle

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2
Q

What are the other names for the TCA cycle?

A

The TCA cycle is known as the Krebs cycle – and also as the citric acid cycle

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3
Q

What are the large moleculesor polymers? What are these large molcules broken down into?

A

Polymers or large molecules - (Proteins, polysaccharides, lipids)

Large molecules are broken down into building blocks (monomers) —— (Amino acids, glucose, glycerol, fatty acids)

Proteins —– Amino acids

Polysaccharides —— Glucose

Lipids —– Glycerol / fatty acids

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4
Q

How to catabolic pathway breakdown large molecule into small molecuses

A

Three stages of catabolic pathway:

Stage1: Polymers or large molecules (Proteins, polysaccharides, lipids) are broken down into building blocks (monomers)

Stage 2: Building blocks (Amino acids, glucose, glycerol, fatty acids) are degraded into the common product (Acetyl-CoA)

Stage 3: Catabolism converges to three principal end products (NH3, H20, CO2)

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5
Q

What are the 3 stages of catablism where large molecules are broken down into small molecules?

A

Three stages of catabolic pathway:

Stage1: Polymers or large molecules (Proteins, polysaccharides, lipids) are broken down into building blocks (monomers)

Stage 2: Building blocks (Amino acids, glucose, glycerol, fatty acids) are degraded into the common product (Acetyl-CoA)

Stage 3: Catabolism converges to three principal end products (NH3, H20, CO2)

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6
Q

What are the three main phases of the TCA cycle?

A

Three main phases of the TCA cycle

Phase 1: Acetyl-CoA production - Organice fuels (glucose, amino acids, fats) are broken down to produce Acetyl-CoA.

Phase 2: Acetyl-CoA oxidation - Acetyl-CoA enters the TCA cycle and is enzymatically oxidized; energy is conserved in electron carriers, NADH and FADH2

Phase 3: Electron Transfer - Electrons carried by the NADH and FADH2 enter the electron transport chain and are able to reduce O2 to make the end product H2O.

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7
Q

What is the TCA cycle

A

TCA cycle

  • Krebs cycle or the citric acid cycle or tricarboxylic acid cycle
  • It is the common pathway to completely oxidize fuel molecules acetyl CoA
  • Acetyl CoA is the product from the oxidative decarboxylation of pyruvate.
  • Acetyl CoA enters the TCA cycle and passes ten steps of reactions that yield energy and CO2.
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8
Q

Where does the TCA occur?

A

The TCA cycle occurs in the mitochondrial membrane

It occurs in the matrix of the mitochondrial membrane

All enzymes of the TCA cycle are in the matrix except for one enzyme

Succinatedehydrogenease is embedded in the cristae of the mictochondria. So this one step occurs in the cristae.

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9
Q

Where are the enzymes of the TCA cycle located?

A

The TCA cycle occurs in the mitochondrial membrane

It occurs in the matrix of the mitochondrial membrane

All enzymes of the TCA cycle are in the matrix except for one enzyme

Succinatedehydrogenease is embedded in the cristae of the mictochondria. So this one step occurs in the cristae.

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10
Q

There is one enzyme of the TCA cycle that isn’t located in the matrix of the mitochondria….what is this enzyme and where is it located.

A

The TCA cycle occurs in the mitochondrial membrane

It occurs in the matrix of the mitochondrial membrane

All enzymes of the TCA cycle are in the matrix except for one enzyme

Succinatedehydrogenease is embedded in the cristae of the mictochondria. So this one step occurs in the cristae.

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11
Q

Does the TCA cycle need or use oxygen?

A

Yes. The TCA cycle does need oxygen.

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12
Q

How much energy does the TCA cycle produce?

A

Per turn of the TCA cycle produces

3 NADH

1 FADH2

1 ATP

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13
Q

What is the reactant of the TCA cycle?

A

the reactant of the TCA cycle

Acetyl-CoA produced from the pyruvate from glycolysis and converted by the
PDH complex.

Citrate is also a reactant, which can come from OAA in the TCA cycle.

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14
Q

What is the product of the TCA cycle?

A

the product of the TCA cycle

In fact since the TCA cycle feed backs into itself there is no net products.

However, TCA cycle produces 3 NADH, 1 FADH2, and 1ATP for each turn.

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15
Q

What is the advantage of the TCA cycle?

A

the advantage of the TCA cycle

The advantage of the TCA cycle is that it can repeat its cycles for several times to accumulate several products which can be either
used as direct energy or put into the oxidative phosphorylation pathway which can
produce large amounts of energy

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16
Q

What does the fate of the pyruvate depend on?

A

The fate of pyruvate depends on the cell energy charge

In cells or tissues with a high energy charge pyruvate is directed toward fatty acid synthesis.

When the energy charge of pyruvate is low, it is preferentially oxidized to CO2 and H2O in the TCA cyle, with the energy generation of 15 equivalent of ATP per pyruvate.

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17
Q

What is the pyruvate dehydrogenease complex?

A

PDH or pyruvate Dehydrogenase complex

The PDH complex is a series of biological step that prepare the pyruvate produced in glycolysis to go into the TCA cycle

These processes chemically convert pyruvate to Acetyl-CoA that can then enter the TCA cycle.

Oxidative decarboxylation of pyruvate is catalyzed by the pyruvate dehydrogenase complex

PDH complex is a noncovalent assembly of three enzymes

PDH complex requires 5 coenzymes

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18
Q

What is necessary before entering the TCA cycle?

A

Pyruvate needs to be converted into Acetyl-CoA.

Acetyl-CoA can enter the TCA cycle

This conversion occurs via the Pyruvate Dehydrogenase complex.

This is known as the Preparatory reaction - this step occurs before the TCA cycle.

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19
Q

Expalin the preparatory reaction of the TCA cycle.

A

The preparatory reaction is the step that occurs before the TCA cycle. This step is preparing for the TCA cycle.

In this step, Pyruvate is converted into Acetyl-CoA

Acetyl-CoA can enter the TCA cycle

This conversion occurs via the Pyruvate Dehydrogenase complex.

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20
Q

What are the reactants for the PDH cycle?

A

Reactamts of the PDH complex

Pyruvate from glycolysis

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21
Q

What is the product of the PDH complex?

A

Product of the PDH complex

Acetyl-CoA

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22
Q

What is the advantage of using the PDH complex

A

Advantage of using the PDH complex

This process allow for the chemical conversion of pyruvate into Acetyl-CoA which can then be inserted into the TCA cycle for processing.

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23
Q

What is the reaction of the PDH complex?

A

Reaction of the PDH complex

Pyruvate + NAD+ + CoA ——> Acetyl CoA + NADH + CO2

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24
Q

What does the PDH complex require?

A

The PDH complex requires

3 enzymes

and

5 coenzymes

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25
Q

What is the structure of pyruvate

A

Pyruvate structure

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26
Q

What is the structure of Acetyl-CoA?

A

Acetyl - CoA structure

Acetyl - CoA is just an acetate attached to Coenzyme A (CoA).

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27
Q

What are the enzymes that are involved in the PDH complex?

A

The PDH complex contains 3 enzymes:

E1 - Pyruvate dehydrogenase

E2 - Dihydrolipoyl Transacetylase

E3 - Dihydrolipoyl dehydrogenase

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28
Q

What are the five coenzymes that are required by the PDH complex?

A

5 coenzymes that are required by the PDH complex:

NAD - Nicotinamide adenine dinucleotide

TPP - Thiamin Pyrophosphate

FAD - Flavin adenine dinucleotide

CoA - Coenzyme A

Lipoate

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29
Q

What is the structure of Coenzyme A

A

Structure of Coenzyme A or CoA

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30
Q

Explain the first step of the PDH complex

A

1st step of the PDH complex

E1 - Pyruvate dehydrogenase

Step 1 reaction:

Pyruvate + Thiamine pyrophosphate (TPP) —–> Hydroxyethyl TPP + CO2

Mechanism:

E1 uses coenzyme, Thiamine pyrophosphate (TPP).

TPP decarboxylates pyruvate to yeild Hydroxyethyl-TPP (HTPP)

Pyruvate losses CO2 and HETPP is formed

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31
Q

Explain the 2nd step of the PDH complex

A

2nd step of the PDH complex

E2 - Dihydrolipoyl transacetylase

Reaction:

HTPP + Lipoyllysine + CoA —–> Dihydrolipolyllysine + Acetyl-CoA

Mechanism:

E2 uses the coenzyme liopic acid

Hydroxyethyl group is transferred to lipoic acid and oxidized to form acetyl dihydrolipoate

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32
Q

Explain the 3rd step of the PDH complex

A

3rd step of the PDH complex

E3 - Dihydrolipoyl dehydrogenase

Reaction:

Dihydroxylipoyllysine + NAD+ ——-> Lipoyllysine + NADH

Mechanism:

E3 enzyme oxidizes dihydrolipoyllysine by transferring the energy rich electrons to an electron carrier, NAD+ via the electron carrier, FAD (coenzyme)

Acetyl group is transferred to CoA

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33
Q

Why is the PDH complex involves so many enzymes and why is it so complex?

A
  1. Enzymatic reaction rates are limited by diffusion, with shorter distance between subunits an enzyme can almost direct the substrate from one subunit (catalytic site) to another
  2. Channeling metabolic intermediates between successive enzymes minimizes side reactions (substrate channeling)
  3. Local substrate concentration is kept high
  4. The reactions of a multienzyme complex can be coordinately controlled / regulated.
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34
Q

Explain thiamine pyrophosphate

A

Thiamine pyrophosphate is a coenzyme that is involved in the pyruvate dehydrogenase complex

TPP assits the first enzyme in the complex. It assits in the decarboxylation of pyruvate. Pyruvate loses CO2

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35
Q

Explain the nicotinamide coenzymes

A

Nicotinamide coenzymes are used in the Pyruvate dehydrogenase complex

NAD+ / NADH and NADP+ / NADPH carry out hydride

(H: -) transfer reactions. All reactions involving these coenzymes are two-electron transfers

36
Q

Explain Flavin coenzymes

A

The flavin coenzymes are used in the pyruvate dehydrogenase complex

FAD / FADH2

Flavin coenzyme can exist in three oxidation states, this allows flavin coenzymes to participate in one-electron and two-electron transfer reactions

Because of this, flavoproteins catalyze many reactions in biological systems and work with many electron donors and acceptors.

37
Q

Explain Coenzyme A and what are the two main functions of CoA

A

Coenzyme A is a coenzyme used in the pyruvate dehydrogenase complex

2 main functions of CoA:

  1. Activation of acyl groups for transfer by nucleophilic attack
  2. Activaton of the alpha-hydrogen of the acyl group for abstraction as a proton
38
Q

How many reactions are in the TCA cycle?

A

The TCA cycle contains a cyclic sequence of 8 enzymes or 8 steps

39
Q

What is the overall reaction of the TCA cycle

A

Overall reaction of the TCA cycle

3NAD+ + FAD + GDP + Pi + acetyl-CoA —-> 3NADH + FADH + GTP + CoA + 2CO2

40
Q

Explain the first step of the TCA cycle

A

1st step of the TCA cycle

Enzyme: Citrate synthase

Reaction: Oxaloacetate + Acetyl-CoA + H2O —-> Citrate + CoA

Description:

  • The main goal of this step is to form citrate
  • This step is known as the condensation reaction.
  • This is a 2 step reaction - an aldol condensation of oxaloacetate and acetyl CoA, followed by hydrolysis to yield citrate and free CoA.
  • Delta G is very large for this reaction because we have a high intermediate and this will help push the reaction forward.
  • This reaction is exergonic - it favors the products
41
Q

What are the structures for the following and how many carbons do each structure have?

Acety-CoA

Oxaloacetate

Citrate

A

Acety-CoA has 2 carbons

Oxaloacetate has 4 carbons

Citrate has 6 carbons

42
Q

What are the different ways the first enzyme of the TCA cycle be regulated.

A

Citrate synthase is the first enzyme of the TCA cycle…it can be regulated by the following different ways

  1. Enzyme is a dimer
    • Active site lies in a cleft between the domains
    • Induced fit induces a conformational change that activiates enzyme
  2. NADH is an allosteric inhibitor
  3. Succinyl-CoA is another inhibitor
43
Q

Why is the first step of the TCA cycle regulaed?

A

The first step of the TCA cycle is known as the first committed step in the cycle.

Being the first committed step, this step has regulatory control mechanims that will effectively regulate the entire cycle

44
Q

What is the 2nd step in the TCA cycle?

A

2nd step in the TCA cycle

Enzyme: Aconitatase

Reaction:

Citrate —> {H2O + cis-Aconitate} —> Isocitrate

Description

  • Aconitase isomerizes citrate to form Isocitrate
  • This step involves moving the hydroxyl group in the citrate molecule so that we can later form an alpha-keto acid
  • This process involes a sequential dehydration and hydration reaction
  • This reaction is endergonic — favors the reactants and not the desired product —- however, the exergonic character of the next reaction helps shift this reaction forward
45
Q

What does the structure of Aconitase contain that is imporatant?

A

Acconitase is an enzyme that is used in the second step of the TCA cyle

Acconitase contains a iron-sulfur center, that acts both in the binding of substrate and the catalytic addition / removal of H2O

46
Q

What blocks the TCA cycle?

A

Fluoroacetate blocks the TCA cycle

Fluroacetate is an extremely poisonous agents and blocks the TCA cycle in vivo

47
Q

Explain fluoroacetate

A

Fluoroacetate blocks the TCA cycle

Fluroacetate is an extremely poisonous agents and blocks the TCA cycle in vivo

Aconitase is inhibited by flurocitrate, which is formed from fluoroacetate

Trojan horse inhibitor — citrate synthase converts it to flurocitrate

48
Q

What is the 3rd step in the TCA cycle?

A

3rd step in the TCA cycle

Enzyme: Isocitrate Dehydrogenase

Reaction:

Isocitrate + NAD —> oxalosuccinate + NADH —-> alpha-ketoglutarate + CO2

Description:

  • TCA cycle contains 2 oxidative decarboxylation steps; this is the first oxidative decarboxylatin step.
  • has 2 reactions
    1. first reaction is oxidation of the alcohol
    2. second reaction is the decarboxylation
49
Q

What does the enzyme Isocitrate dehydrogenase do?

A

Enzyme Isocitrate dehydrogenase is the 3rd enzyme used in the TCA cycle.

This reaction goes from Isocitrate to alpha-ketoglutarate

This enzyme removes a hydride ion

This reaction requires a NADH

50
Q

How is Isocitrate Dehydrogenase regulated?

A

Isocitrate dehydrogenase is the third enzyme used in the TCA cycle

It is used to go from Isocitrate to alpha-ketoglutarate

Regulation of Isocitrate dehydrogenase

  • Connects the TCA cycle to the electron trnasport chain
  • Reaction is regulated
    • NADH allosterically inhibits enzyme
    • ATP allosterically inhibits enzyme
  • Lowers the Km for isocitrate
51
Q

What is the 4th step in the TCA cycle?

A

Step 4 of the TCA cycle

Enzyme: Ketoglutarate dehydrogenase

This reaction uses the ketoglutarate dehydrogenase comple — which is similar to the pyruvate dehydrogenase complex.

Descritpion

  • oxidation of alpha-ketoglutarate to succinyl-CoA and CO2
  • This multi-step reaction is performed by the ketoglutarate dehydrogenase that involves
    • 3 enzymes - E1, E2, E3
    • 5 coenzymes - TPP, FAD, CoA-SH, lipoic acid, NAD+
52
Q

How is the 4th step in the TCA cycle similar to the prepratory step before the TCA cycle?

A

These two are similar because the 4th step of the TCA cycle involves the ketoglutarate dehydrogenase complex which is similar to the pyruvate dehydrogenase complex in the prepratory step

Ketoglutarate dehydrogenase complex invlvoes

3 enzymes - E1, E2, E3

5 COfactors - TPP, CoA-SH, Lipoic acid, NAD+, FAD

53
Q

Give a brief summary of the TCA cycle from step 1 to step 4…what has occured up to this point?

A

TCA cycle from step 1 to step 4

  • Glucose has been completely oxidized into carbon dioxide
  • NADH has been sent to the electron transport chain or some NADPH has been made to perform anabolic reactions

2 carbons have been added to Oxaloacetate by the action of citrate synthase and Acetyl-CoA

2 carbons have been lost as CO2 by oxidative decarboylation steps

2 Oxidized NAD+ cofactors have been reduced to NADH

54
Q

What is the overview of what happens between the step 5 to step 8 of the TCA cycle?

A

The remaning half the TCA cycle (step 5 to step 8), the Succinyl-CoA is converted back into the original substrate for the cycle: Oxaloacetate

55
Q

What is the 5th step in the TCA cycle

A

5th step in the TCA cycle

Enzyme: Succinyl-CoA synthetase

Reaction: Succinyl-CoA + GDP + Pi —> Succinate + GTP + CoASH

Description:

  • Known as the subrate-level phosphorylation
  • Succinyl-CoA is a high potential energy molecule
  • Generates ATP or GTP
  • Hydrolysis of CoA ester drives phosphorylation to make either GTP (animals) or ATP (Plants and bacteria)
56
Q

Why is reaction 5 of the TCA cycle a high energy yeilding reaction?

A

Reaction 5 of the TCA cycle, consists of the Succinyl-CoA which is a high energy yielding molecule.

This step has enough energy to make a nucleoside triphosphate

Hydrolysis of CoA ester drives phosphorylation to make either GTP in anaimals and ATP in plants and bacteria

Most of the GTP that is formed is used in the formation of ATP, by the action of Nucleoside Diphosphokinase

GTP + ADP <<<——Neucleo Diphosphokinase—->>> GDP + ATP

57
Q

What is the 6th step in the TCA cycle?

A

6th step in the TCA cycle

Enzyme: Succinate Dehydrogenase

Reaction:

Succinate + FAD —-> Fumarate + FADH2

Descritpion

  • This reaction involves the Oxidation of succinate to fumarate
  • Starting from succinate, two hydrogen atoms leave to an acceptor, FAD and the reaction yeields fumerate
  • This reaction involves take a single bond and converting it into a double bond
  • Succinate dehydrogenase is actually part of the electron transport chain
  • Electrons pass from succinate to FAD (FADH) and then directly to ubiquinone
58
Q

What does succinate dehydrogenase contain that is important?

A

Succinate dehydrogenase is the 6th enzyme involved in the TCA cycle.

It oxidizes Succinate to fumarate

Succinate dehydrogenase contains several iron-sulfur centers that mediate the flow of electron from succinate via FAD to the respiratory chain and finally to O2.

59
Q

What is the 7th reaction of the TCA cycle?

A

7th reaction of the TCA cycle

Enzyme: Fumarase

Reaction: Fumarate + H2O —-> L-Malate

Description:

  • This is a hydration reaction.
  • Water is added across the double bond
  • Fumarase is a stereo-specific enzyme - it will only hydrate fumarate
60
Q

What is the 8th reaction of the TCA cycle?

A

8th reaction of the TCA cycle

Enzyme: Malate Dehydrogenase

Reaction: L-Malate + NAD+ ———-> Oxyloacetate + NADH + H+

Description:

  • L-Malate is dehydrogenated to produce oxaloacetate
  • This dehydrogenation reaction will regenerate oxaloacetate
  • This is a highly endergonic reaction and so it favors the reactants over the products
  • However, the next step which is the first step in the TCA cycle is highly exergonic reaction and this keeps the levels of oxaloacetate low thus allowing the this above reaction to proceed
61
Q

In the structure shown below….which part of the structure is the malate and which part is the NAD+

A

This structure is the active of the malate dehydrogenase

Malate is shown in yellow

NAD+ is shown in pink

62
Q

What is the overall reaction of the TCA cycle — energy consequences

A

Acetyl-CoA + 3 NAD+ + FAD + ADP + Pi + 2H2O ——> 2CO2 + 3 NADH + 3H+ + FADH2 + ATP + CoASH

63
Q

What is the reaction / energy consequenses for catabolism of glucose through glycolysis and the TCA cycle

A

Glucose + 2 H2O + 10NAD+ + 2 FAD + 4 ADP + 4 Pi ——-> 10 NADH + 6CO2 + 10 H+ + 2 FADH2 + 4 ATP

64
Q

How many ATP do you get from the following two energy rich molecules?

NADH

FADH2

A

NADH produces 3 ATP

FADH2 produces 2 ATP

65
Q

What is the total net yield of ATP per glucose

A

Total net ATP yield per glucose = 38 ATP

Reaction: 10 NADH + 4 ATP + 2 FADH2

NADH prodeuces 3 ATP

FADH2 produces 2 ATP

(10 X 3) + (2 x 2) + 4 = 38 ATP per glucose

66
Q

The carbons atoms of the Acety-CoA have different fates in the TCA cycle

A

The carbons atoms of the Acety-CoA have different fates in the TCA cycle

  • The carbonyl C of acetyl-CoA turns to CO2 only in the second turn of the cycle (following entry of acetyl-CoA )
  • The methyl C of acetyl-CoA survives two cycles completely, but half of what’s left exits the cycle on each turn after that
  • The C-C bond cleaved in a given TCA cycle actually entered as an acetate in the previous turn
  • Thus the oxidative decarboxylations that cleave this bond are just a disguised acetate C-C cleavage and oxidation
67
Q

What are the other roles of the TCA cycle?

A

The other roles of the TCA cycle:

  • TCA is oxidizing glucose and providing NADH for the electron transport chain
  • However, TCA cycle can also be used in anabolic pathways
    • α-Ketoglutarate is transaminated to make glutamate, which can be used to make purine nucleotides, Arg and Pro
    • Succinyl-CoA can be used to make porphyrins
    • Fumarate and oxaloacetate can be used to make several amino acids and also pyrimidine nucleotides
  • The TCA cycle also can provide intermediates for biosynthesis.
68
Q

How does the TCA cycle play a role in the anabolic pathways? How is the TCA cycle used in the anabolic pathways?

A

TCA cycle can also be used in anabolic pathways

  • α-Ketoglutarate is transaminated to make glutamate, which can be used to make purine nucleotides, Arg and Pro
  • Succinyl-CoA can be used to make porphyrins
  • Fumarate and oxaloacetate can be used to make several amino acids and also pyrimidine nucleotides
69
Q

Explain what anaplerotic reactions mean

A

Anaplerotic reactions

Cells have mechanisms to refill the pools of the citric acid cycle intermediates. These pathways are referred to as the anapleurotic reactions.

70
Q

List the different types of Anaplerotic reactions

A
  • Pyruvate carboxylase -
  • PEP carboxylase -
  • Malic enzyme
71
Q

Expalin each of the anaplerotic reactions

A
  • Pyruvate carboxylase -
  • converts pyruvate to oxaloacetate
  • This is the most important anaplerotic reaction
  • PEP carboxylase -
  • converts PEP to oxaloacetate
  • Malic enzyme
  • converts pyruvate into malate
  • PEP carboxykinase -
  • could have been an anaplerotic reaction, but it goes the wrong way
  • CO2 binds weakly to PEP carboxykinase, but oxaloacetate binds tightly, so the reaction goes spontaneously in the opposite direction.
72
Q

Why can’t PEP carboxykinase be an anaplerotic reaction?

A

PEP carboxykinase -

  • could have been an anaplerotic reaction, but it goes the wrong way
  • CO2 binds weakly to PEP carboxykinase, but oxaloacetate binds tightly, so the reaction goes spontaneously in the opposite direction.
73
Q

What is the reaction for the pyruvate carboxylase?

A

Pyruvate carboxylase -

Pyruvate carboxylase an anaplerotic reaction

converts pyruvate to oxaloacetate
This is the most important anaplerotic reaction

74
Q

What is the reaction for the PEP carboxylase?

A

PEP carboxylase -

PEP carboxylase is an anaplerotic reaction

converts PEP to oxaloacetate

75
Q

What is the reaction for the Malic enzyme?

A

Malic enzyme

Malic enzyme is an anaplerotic reaction

converts pyruvate into malate

76
Q

What is the reaction for the PEP carboxykinase?

A

PEP carboxykinase

PEP carboxykinase cannot be an anaplerotic reaction

77
Q

What is the reductive TCA cycle?

A

Reductive TCA cycle is the TCA cycle running backwards

It is a reversed TCA cycle

78
Q

Explain the reductive TCA cycle

A
  • The TCA cycle running backward could assimilate CO2
  • This may have been the first metabolic pathway
  • This “reductive TCA cycle” occurs in certain extant archaea and bacteria, where it serves all their carbon needs
  • Energy to drive it? Maybe reaction of FeS with H2S to form FeS2 (iron pyrite)
  • Iron pyrite, which was plentiful in ancient times, is an ancient version of ‘iron-sulfur clusters’ found in many enzymes today!
79
Q

At what steps is the TCA cycle regulated?

A

TCA cycle regulation:

  1. Pyruvate Dehydrogenase
  2. Citrate synthase
  3. Isocitrate dehydrogenase
  4. Alpha-ketoglutarate dehydrogenase
80
Q

How is the TCA cycle regulated at these different steps?

A

TCA cycle regulation:

Pyruvate Dehydrogenase

  • Acetyl-CoA inhibits
  • NADH inhibits
  • ATP inhibits
  • NAD+, CoA activate

Citrate synthase

  • ATP inhibit
  • NADH inhibit
  • Succinyl-CoA inhibit

Isocitrate dehydrogenase

  • ATP inhibit
  • NADH inhibit
  • ADP activate

Alpha-ketoglutarate dehydrogenase

  • NADH inhibit
  • Succinyl-CoA inhibit
  • AMP activates
81
Q

How is pyruvate dehydrogenase regulated?

A

Pyruvate Dehydrogenase is regulated by phosphorylation / Dephosphorylation

Phosphorylation inactivates

Dephosphorylation activates

82
Q

What two enzymes regulate the pyruvate dehydrogenase?

A

Pyruvate dehydrogenase Kinase

  • Allosterically Activated by NADH and Acetyl CoA
  • High concentrations stimulated phosphorylation of a serine on PDH
  • Pyruvate dehydrogenase kinase then phosphorylates pyruvate dehydrogenase resulting in its inhibition

Pyruvate dehydrogenase phosphatase

  • Active in the presense of low NADH to NAD+ ratios and low acetyl-CoA
83
Q

How does isocitrate dehydrogenase regulate the TCA cycle?

A
  • Citrate:Isocitrate level control the production of cytosolic acetyl-CoA
  • Isocitrate Dehydrogenase when turned on will pull reactions in the TCA cycle
  • When turned off anabolic reactions of Acetyl-CoA in the cytoplasm will be favored
84
Q

What is the glyoxylate cycle?

A

In many organisms, other than vertebrates, the glyoxylate cycle serves as mechanism for converting acetate to carbohydrates

The glyoxylate cycle produces four-carbon compounds from acetate

85
Q

Explain the glyoxylate cycle and how acetate is used as a carbon source.

A
  • Acetate-based growth - net synthesis of carbohydrates and other intermediates from acetate - is not possible with TCA
  • The glyoxylate cycle offers a solution for plants and some bacteria and algae
  • The CO2-evolving steps are bypassed and an extra acetate is utilized
  • Isocitrate lyase and malate synthase are the short-circuiting enzymes
  • Isocitrate lyase produces glyoxylate and succinate
  • Malate synthase does a Claisen condensation of acetyl-CoA and the aldehyde group of glyoxylate - classic CoA chemistry!
  • The glyoxylate cycle helps plants grow in the dark! Seeds are a rich source of acetate (from fatty acids). Until the nascent plant sees the sun (and begins photosynthesis), it can grow using the glyoxylate cycle
86
Q

In plants,where are the glyoxylate cycle enzymes found?

A

In plants the glyoxylate cycle enzymes are found in the membrane-bound organelles —–> glyoxysomes

87
Q

Explain Glyoxysomes?

A

In plants the glyoxylate cycle enzymes are found in the membrane-bound organelles —–> glyoxysomes

Glyoxysomes Must Borrow Three Reactions from Mitochondria

  • Glyoxysomes: Plant organelles where the glyoxylate cycle occurs
  • Glyoxysomes do not contain all the enzymes needed to run the glyoxylate cycle
  • Succinate dehydrogenase, fumarase, and malate dehydrogenase are absent
  • Glyoxysomes borrow these three reactions from mitochondria, so that they can convert succinate to oxaloacetate