Chapter 19 = TCA cycle

Question 1

What does the TCA cycle stand for?

Answer 1

TCA cycle = Tricarboxylic Acid Cycle

Question 2

What are the other names for the TCA cycle?

Answer 2

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

Question 3

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

Answer 3

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

Question 4

How to catabolic pathway breakdown large molecule into small molecuses

Answer 4

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)

Question 5

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

Answer 5

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)

Question 6

What are the three main phases of the TCA cycle?

Answer 6

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.

Question 7

What is the TCA cycle

Answer 7

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.

Question 8

Where does the TCA occur?

Answer 8

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.

Question 9

Where are the enzymes of the TCA cycle located?

Answer 9

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.

Question 10

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.

Answer 10

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.

Question 11

Does the TCA cycle need or use oxygen?

Answer 11

Yes. The TCA cycle does need oxygen.

Question 12

How much energy does the TCA cycle produce?

Answer 12

Per turn of the TCA cycle produces

3 NADH

1 FADH2

1 ATP

Question 13

What is the reactant of the TCA cycle?

Answer 13

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.

Question 14

What is the product of the TCA cycle?

Answer 14

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.

Question 15

What is the advantage of the TCA cycle?

Answer 15

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

Question 16

What does the fate of the pyruvate depend on?

Answer 16

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.

Question 17

What is the pyruvate dehydrogenease complex?

Answer 17

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

Question 18

What is necessary before entering the TCA cycle?

Answer 18

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.

Question 19

Expalin the preparatory reaction of the TCA cycle.

Answer 19

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.

Question 20

What are the reactants for the PDH cycle?

Answer 20

Reactamts of the PDH complex

Pyruvate from glycolysis

Question 21

What is the product of the PDH complex?

Answer 21

Product of the PDH complex

Acetyl-CoA

Question 22

What is the advantage of using the PDH complex

Answer 22

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.

Question 23

What is the reaction of the PDH complex?

Answer 23

Reaction of the PDH complex

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

Question 24

What does the PDH complex require?

Answer 24

The PDH complex requires

3 enzymes

and

5 coenzymes

Question 25

What is the structure of pyruvate

Answer 25

Pyruvate structure

Question 26

What is the structure of Acetyl-CoA?

Answer 26

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

Question 27

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

Answer 27

The PDH complex contains 3 enzymes: E1 - Pyruvate dehydrogenase E2 - Dihydrolipoyl Transacetylase E3 - Dihydrolipoyl dehydrogenase

Question 28

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

Answer 28

5 coenzymes that are required by the PDH complex: NAD - Nicotinamide adenine dinucleotide TPP - Thiamin Pyrophosphate FAD - Flavin adenine dinucleotide CoA - Coenzyme A Lipoate

Question 29

What is the structure of Coenzyme A

Answer 29

Structure of Coenzyme A or CoA

Question 30

Explain the first step of the PDH complex

Answer 30

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

Question 31

Explain the 2nd step of the PDH complex

Answer 31

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

Question 32

Explain the 3rd step of the PDH complex

Answer 32

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

Question 33

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

Answer 33

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.

Question 34

Explain thiamine pyrophosphate

Answer 34

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

Question 35

Explain the nicotinamide coenzymes

Answer 35

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

Question 36

Explain Flavin coenzymes

Answer 36

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.

Question 37

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

Answer 37

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

Question 38

How many reactions are in the TCA cycle?

Answer 38

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

Question 39

What is the overall reaction of the TCA cycle

Answer 39

Overall reaction of the TCA cycle 3NAD⁺ + FAD + GDP + P_i + acetyl-CoA ----\> 3NADH + FADH + GTP + CoA + 2CO²

Question 40

Explain the first step of the TCA cycle

Answer 40

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

Question 41

What are the structures for the following and how many carbons do each structure have? Acety-CoA Oxaloacetate Citrate

Answer 41

Acety-CoA has 2 carbons ## Footnote Oxaloacetate has 4 carbons Citrate has 6 carbons

Question 42

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

Answer 42

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

Question 43

Why is the first step of the TCA cycle regulaed?

Answer 43

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

Question 44

What is the 2nd step in the TCA cycle?

Answer 44

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

Question 45

What does the structure of Aconitase contain that is imporatant?

Answer 45

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

Question 46

What blocks the TCA cycle?

Answer 46

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

Question 47

Explain fluoroacetate

Answer 47

Fluoroacetate blocks the TCA cycle ## Footnote 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

Question 48

What is the 3rd step in the TCA cycle?

Answer 48

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

Question 49

What does the enzyme Isocitrate dehydrogenase do?

Answer 49

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

Question 50

How is Isocitrate Dehydrogenase regulated?

Answer 50

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

Question 51

What is the 4th step in the TCA cycle?

Answer 51

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+

Question 52

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

Answer 52

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

Question 53

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

Answer 53

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

Question 54

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

Answer 54

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

Question 55

What is the 5th step in the TCA cycle

Answer 55

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)

Question 56

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

Answer 56

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

Question 57

What is the 6th step in the TCA cycle?

Answer 57

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

Question 58

What does succinate dehydrogenase contain that is important?

Answer 58

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.

Question 59

What is the 7th reaction of the TCA cycle?

Answer 59

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

Question 60

What is the 8th reaction of the TCA cycle?

Answer 60

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

Question 61

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

Answer 61

This structure is the active of the malate dehydrogenase Malate is shown in yellow NAD+ is shown in pink

Question 62

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

Answer 62

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

Question 63

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

Answer 63

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

Question 64

How many ATP do you get from the following two energy rich molecules? NADH FADH2

Answer 64

NADH produces 3 ATP FADH2 produces 2 ATP

Question 65

What is the total net yield of ATP per glucose

Answer 65

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

Question 66

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

Answer 66

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

Question 67

What are the other roles of the TCA cycle?

Answer 67

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.

Question 68

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

Answer 68

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

Question 69

Explain what anaplerotic reactions mean

Answer 69

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

Question 70

List the different types of Anaplerotic reactions

Answer 70

* Pyruvate carboxylase - * PEP carboxylase - * Malic enzyme

Question 71

Expalin each of the anaplerotic reactions

Answer 71

* 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.

Question 72

Why can't PEP carboxykinase be an anaplerotic reaction?

Answer 72

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.

Question 73

What is the reaction for the pyruvate carboxylase?

Answer 73

Pyruvate carboxylase - Pyruvate carboxylase an anaplerotic reaction converts pyruvate to oxaloacetate This is the most important anaplerotic reaction

Question 74

What is the reaction for the PEP carboxylase?

Answer 74

PEP carboxylase - PEP carboxylase is an anaplerotic reaction converts PEP to oxaloacetate

Question 75

What is the reaction for the Malic enzyme?

Answer 75

Malic enzyme Malic enzyme is an anaplerotic reaction converts pyruvate into malate

Question 76

What is the reaction for the PEP carboxykinase?

Answer 76

PEP carboxykinase PEP carboxykinase cannot be an anaplerotic reaction

Question 77

What is the reductive TCA cycle?

Answer 77

Reductive TCA cycle is the TCA cycle running backwards It is a reversed TCA cycle

Question 78

Explain the reductive TCA cycle

Answer 78

* 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!

Question 79

At what steps is the TCA cycle regulated?

Answer 79

TCA cycle regulation: 1. Pyruvate Dehydrogenase 2. Citrate synthase 3. Isocitrate dehydrogenase 4. Alpha-ketoglutarate dehydrogenase

Question 80

How is the TCA cycle regulated at these different steps?

Answer 80

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

Question 81

How is pyruvate dehydrogenase regulated?

Answer 81

Pyruvate Dehydrogenase is regulated by phosphorylation / Dephosphorylation Phosphorylation inactivates Dephosphorylation activates

Question 82

What two enzymes regulate the pyruvate dehydrogenase?

Answer 82

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

Question 83

How does isocitrate dehydrogenase regulate the TCA cycle?

Answer 83

* 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

Question 84

What is the glyoxylate cycle?

Answer 84

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

Question 85

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

Answer 85

* 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

Question 86

In plants,where are the glyoxylate cycle enzymes found?

Answer 86

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

Question 87

Explain Glyoxysomes?

Answer 87

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