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biochem sem 2 > week 14 > Flashcards

week 14 Flashcards

1
Q

What are the two main types of metabolic pathways in our cells?

A

Catabolic pathways and anabolic pathways

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2
Q

What is the primary function of catabolic pathways?

A

Catabolic pathways are responsible for breaking down molecules to produce energy.

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3
Q

What is the goal of catabolic pathways?

A

One of the main goals of catabolic pathways is to generate reducing cofactors, specifically NADH and FADH2.

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4
Q

What role do reducing cofactors like NADH and FADH2 play?

A

Reducing cofactors activate the electron transport chain

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5
Q

Where does the electron transport chain occur?

A

The electron transport chain takes place in the mitochondria

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6
Q

What does the electron transport chain use the energy from NADH and FADH2 for?

A

The energy from NADH and FADH2 is used to produce a large amount of ATP through oxidative phosphorylation.

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7
Q

Why is ATP important?

A

ATP is the energy currency of our cells and is required for various cellular activities.

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8
Q

How do reducing cofactors and the electron transport chain contribute to ATP production?

A

When catabolic pathways produce NADH and FADH2, these reducing cofactors activate the electron transport chain, which leads to the production of a significant amount of ATP through oxidative phosphorylation.

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9
Q

What are some other names for the citric acid cycle?

A

The citric acid cycle is also known as the Krebs cycle or the tricarboxylic acid (TCA) cycle

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10
Q

What is the citric acid cycle?

A

The citric acid cycle is a metabolic pathway in our cells.

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11
Q

What is the role of the citric acid cycle?

A

The citric acid cycle is a key part of cellular respiration and is responsible for generating energy from nutrients.

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12
Q

What process is the citric acid cycle a part of?

A

The citric acid cycle is a part of cellular respiration

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13
Q

How does the citric acid cycle contribute to cellular energy production?

A

The citric acid cycle helps generate energy from nutrients during cellular respiration

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14
Q

Why do we have metabolic pathways in addition to glycolysis?

A

These additional metabolic pathways are needed to extract and utilize the remaining energy from glucose

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15
Q

What happens to pyruvate after glycolysis?

A

Pyruvate undergoes another set of metabolic pathways called pyruvate oxidation

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16
Q

Where does pyruvate oxidation take place?

A

Pyruvate oxidation occurs inside the mitochondria, which are the powerhouses of our cells

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17
Q

What is the purpose of pyruvate oxidation?

A

Pyruvate oxidation further breaks down pyruvate to release more energy in the form of ATP and NADH

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18
Q

Why are these additional metabolic pathways necessary?

A

These pathways ensure that we can fully utilize the energy stored in pyruvate and maximize the amount of energy obtained from glucose

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19
Q

How does pyruvate oxidation help us get the most energy from glucose?

A

By going through pyruvate oxidation, we can unlock and use all of the stored energy in pyruvate, ensuring that we don’t waste the remaining energy from glucose

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20
Q

Why is it important for our cells to have enough energy?

A

Cells require sufficient energy to perform their functions and carry out various cellular processes

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21
Q

What is cellular respiration?

A

Cellular respiration is a process in which cells use oxygen to produce energy and release carbon dioxide

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22
Q

How does our body maintain stable blood pH levels during cellular respiration?

A

Our body relies on the bicarbonate buffer system to safely remove the carbon dioxide produced and maintain stable blood pH levels. The elimination of carbon dioxide primarily occurs through exhalation from the lungs

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23
Q

What are the three stages of cellular respiration?

A

The three stages of cellular respiration are acetyl-CoA production, acetyl-CoA oxidation, and oxidative phosphorylation

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24
Q

What happens in the first stage of cellular respiration?

A

In the first stage, various nutrients, including glucose, fatty acids, and amino acids, are converted into a molecule called acetyl-CoA. This stage activates the citric acid cycle and generates cofactors such as ATP, NADH, and FADH2

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25
Q

How is acetyl-CoA oxidized in the second stage?

A

In the second stage, the acetyl group in acetyl-CoA is released as two carbon dioxide (CO2) molecules. This stage also generates NADH, FADH2, and one molecule of GTP

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26
Q

What is the significance of the intermediate structure formed during acetyl-CoA oxidation?

A

The two carbons from acetyl-CoA are not immediately released but become part of an intermediate structure. It takes several more rounds of reactions to eventually release those carbons

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27
Q

What is the final stage of cellular respiration?

A

The final stage is oxidative phosphorylation, which is responsible for generating the majority of ATP during the breakdown of molecules. It involves the transfer of electrons from NADH and FADH2 to create a flow of protons and the production of ATP through phosphorylation

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28
Q

What are some of the cofactors generated during cellular respiration?

A

ATP, NADH, and FADH2 are some of the cofactors generated during cellular respiration

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29
Q

Where is most of the ATP produced in cellular respiration?

A

Most of the ATP is produced in the final stage of cellular respiration, oxidative phosphorylation

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30
Q

Why is cellular respiration important for organisms?

A

Cellular respiration is essential because it provides organisms with energy needed for various cellular activities.

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31
Q

How does cellular respiration contribute to ATP production?

A

Cellular respiration generates more ATP from glucose compared to glycolysis alone. It also enables the extraction of energy from lipids and amino acids. ATP is a molecule that stores and supplies energy for cellular processes.

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32
Q

How far back can the origins of cellular respiration be traced?

A

The origins of cellular respiration can be traced back approximately 2.5 billion years ago.

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33
Q

What was the primary mode of energy production before cellular respiration evolved?

A

Before cellular respiration evolved, anaerobic glycolysis, a process that doesn’t require oxygen, was the primary mode of energy production.

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34
Q

What led to the evolution of cellular respiration?

A

The increase in oxygen content in the atmosphere, facilitated by the rise of cyanobacteria and their release of oxygen as a byproduct of photosynthesis, led to the evolution of cellular respiration.

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35
Q

Which organisms utilize cellular respiration?

A

Cellular respiration is utilized by various organisms, including animals, plants, and many microorganisms.

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36
Q

What are the three major stages of cellular respiration?

A

The three major stages of cellular respiration are acetyl-CoA production, acetyl-CoA oxidation, and electron transfer with oxidative phosphorylation.

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37
Q

How would you describe cellular respiration in simpler terms?

A

Cellular respiration is a process that breaks down glucose, fats, and proteins to provide organisms with a lot of energy. It started when the Earth had less oxygen, and as oxygen levels increased, organisms developed cellular respiration to harness even more energy. Animals, plants, and many tiny organisms use this process, which occurs in three main steps: acetyl-CoA production, breaking down acetyl-CoA, and transferring electrons to create ATP.

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38
Q

Where does oxidative decarboxylation occur?

A

Oxidative decarboxylation takes place in cells that have mitochondria.

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39
Q

What is the function of mitochondria in cells?

A

Mitochondria act as power stations in cells and are responsible for producing ATP energy.

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40
Q

Are mitochondria present in all cells?

A

Most cells in our body have mitochondria, but there are some cells that do not.

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41
Q

Why are mitochondria important for energy production?

A

Mitochondria play a crucial role in the full oxidation processes in our body, which involve the complete breakdown of molecules to generate energy. They are necessary for efficient energy production.

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42
Q

Can you explain oxidative decarboxylation in simpler terms?

A

Oxidative decarboxylation is a process that converts pyruvate into Acetyl-CoA and occurs in cells with mitochondria. Mitochondria are like power stations in cells, producing energy in the form of ATP. Most cells in our body have mitochondria, which are essential for breaking down molecules and generating energy.

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43
Q

Where is pyruvate produced?

A

Pyruvate is produced during glycolysis, which occurs in the cytosol of the cell.

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44
Q

Why does pyruvate need to be transported into the mitochondria?

A

Pyruvate needs to be transported into the mitochondria for further processing and energy generation.

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45
Q

How does pyruvate enter the mitochondria?

A

Pyruvate can pass through large openings in the outer mitochondrial membrane called porins.

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46
Q

What is the role of the mitochondrial pyruvate carrier?

A

The mitochondrial pyruvate carrier is a transport protein that facilitates the entry of pyruvate into the matrix of the mitochondria.

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47
Q

What happens when the genes coding for the mitochondrial pyruvate carrier are mutated?

A

Mutations in these genes can hinder the normal transport of pyruvate into the mitochondria, leading to increased lactate production and potentially contributing to the Warburg effect observed in certain types of cancers.

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48
Q

What is the Warburg effect?

A

The Warburg effect refers to the abnormal production of lactate by lactate dehydrogenase in cancer cells, even in the presence of oxygen. It is associated with mutations in the mitochondrial pyruvate carrier and the upregulation of glycolysis enzymes.

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49
Q

Why is lactate production increased in cancer cells?

A

Increased lactate production in cancer cells can be caused by mutations in transporters that hinder pyruvate transport into the mitochondrial matrix, as well as the upregulation of glycolysis enzymes.

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50
Q

What is the function of the pyruvate dehydrogenase complex?

A

The pyruvate dehydrogenase complex converts pyruvate into acetyl-CoA

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51
Q

How is the pyruvate dehydrogenase complex structured?

A

The complex is large and highly structured, consisting of three different enzymes and multiple copies in the cell.

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52
Q

How does the size of the pyruvate dehydrogenase complex compare to ribosomes?

A

The pyruvate dehydrogenase complex is approximately three times larger than ribosomes.

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53
Q

What is substrate channeling?

A

Substrate channeling is when the specific substrate, in this case, pyruvate, remains bound to the enzyme as it undergoes a series of reactions in different active sites, ensuring efficient conversion without any loss or interruptions.

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54
Q

How is the pyruvate dehydrogenase complex regulated?

A

The regulation of a single protein subunit within the complex can influence the entire production of the product, allowing for easy regulation.

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55
Q

What is the advantage of having a large enzyme complex like the pyruvate dehydrogenase complex?

A

The constant binding of intermediates to the enzyme complex allows for faster reactions and effective regulation.

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56
Q

In which types of cells is the pyruvate dehydrogenase complex found?

A

The pyruvate dehydrogenase complex is present in all cells that have mitochondria. In bacteria, a similar complex is found in the cytosol since bacteria lack mitochondria.

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57
Q

What is the purpose of oxidative decarboxylation?

A

Oxidative decarboxylation converts pyruvate into acetyl-CoA, a molecule crucial for the citric acid cycle.

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58
Q

What enzymes make up the pyruvate dehydrogenase complex?

A

The pyruvate dehydrogenase complex consists of three enzymes: pyruvate dehydrogenase (E1), dihydrolipoyl transacetylase (E2), and dihydrolipoyl dehydrogenase (E3).

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59
Q

What are the cofactors required for the pyruvate dehydrogenase complex to function properly?

A

the complex requires five cofactors, four of which are vitamins. These vitamins are part of the B-group vitamins and serve as precursors for coenzymes NAD and FAD.

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60
Q

What is the role of lipoate in the pyruvate dehydrogenase complex?

A

Lipoate is a special cofactor in the complex that acts as a long arm to pick up and transfer hydroxyethyl groups between different active sites, efficiently guiding and transferring the substrate.

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61
Q

How does pyruvate undergo decarboxylation in the process?

A

During oxidative decarboxylation, a carbon dioxide molecule is removed from pyruvate, resulting in the formation of an acetyl group.

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62
Q

What happens to the acetyl group during the pyruvate dehydrogenase complex reaction?

A

The acetyl group is added to thiamine pyrophosphate (TPP) and forms a thioester bond with lipoate before being transferred to coenzyme A (CoA) to form acetyl-CoA.

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63
Q

What is the rate-limiting enzyme in oxidative decarboxylation?

A

The pyruvate dehydrogenase complex is the rate-limiting enzyme in oxidative decarboxylation.

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64
Q

How is lipoate restored to its initial state after the reaction?

A

The thiol groups in lipoate are oxidized, facilitated by FAD, resulting in the regeneration of lipoate. FADH2 then passes the hydrogens to NAD, creating the reducing cofactor NADH+H+.

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65
Q

What can NADH+H+ contribute to in the mitochondria?

A

NADH+H+ can move to other parts of the mitochondria, particularly the electron transport chain, and contribute to ATP production.

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66
Q

What is the overall purpose of oxidative decarboxylation?

A

The purpose of oxidative decarboxylation is to convert pyruvate into acetyl-CoA, a key molecule that initiates the citric acid cycle and is involved in energy production.

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67
Q

What is the pyruvate dehydrogenase complex responsible for?

A

The pyruvate dehydrogenase complex is responsible for the oxidative decarboxylation of pyruvate.

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68
Q

What are the enzymes involved in the pyruvate dehydrogenase complex?

A

Enzyme 1, Enzyme 2, and Enzyme 3 are involved in the pyruvate dehydrogenase complex.

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69
Q

What happens in Step 1 of Enzyme 1?

A

Step 1 involves the decarboxylation of pyruvate, converting it into an aldehyde.

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70
Q

What occurs in Step 2 of Enzyme 1?

A

Step 2 involves the oxidation of the hydroxyethyl group to acetate, while electrons reduce lipoamide and form a thioester.

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71
Q

What is the outcome of Step 3 in Enzyme 2?

A

Step 3 results in the formation of acetyl-CoA, which is the first product.

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72
Q

What processes take place in Enzyme 3?

A

Enzyme 3 is involved in Step 4, which is the reoxidation of the lipoamide cofactor, and Step 5, which is the regeneration of the oxidized FAD cofactor, resulting in the formation of NADH, the second product.

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73
Q

What deficiency can be associated with the pyruvate dehydrogenase complex?

A

Deficiencies in the pyruvate dehydrogenase complex can result from mutations in proteins within the complex or a lack of vitamin B1 (thiamine).

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74
Q

What is the common deficiency known as berry berry disease caused by?

A

Berry berry disease is caused by a lack of vitamin B1 (thiamine) in the diet.

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75
Q

How does the deficiency of vitamin B1 impact the pyruvate dehydrogenase complex?

A

Without vitamin B1, the pyruvate dehydrogenase complex cannot perform the conversion of glucose into acetyl coenzyme A.

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76
Q

What are the consequences of the pyruvate dehydrogenase complex deficiency?

A

The deficiency leads to neurological damage and impairs the brain’s ability to utilize glucose efficiently, impacting its energy production.

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77
Q

What is the first step in the citric acid cycle?

A

The first step in the citric acid cycle is the condensation of Acetyl-CoA and oxaloacetate.

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78
Q

What is formed as a result of the condensation of Acetyl-CoA and oxaloacetate?

A

The formation of citrate occurs as a result of the condensation of Acetyl-CoA and oxaloacetate.

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79
Q

Where does Acetyl-CoA come from?

A

Acetyl-CoA is derived from the breakdown of glucose or fats.

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80
Q

What is the role of citrate synthase in the citric acid cycle?

A

Citrate synthase is the enzyme that helps in joining Acetyl-CoA and oxaloacetate to form citrate.

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81
Q

What is released during the condensation of Acetyl-CoA and oxaloacetate?

A

Coenzyme A (CoA) is released during the condensation of Acetyl-CoA and oxaloacetate.

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82
Q

Where does the citric acid cycle take place?

A

The citric acid cycle takes place in the mitochondria of cells.

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83
Q

What is the purpose of the citric acid cycle?

A

The citric acid cycle helps in the breakdown of carbohydrates, fats, and proteins to produce energy.

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84
Q

What energy-rich molecules are generated in the citric acid cycle?

A

NADH and FADH2 are energy-rich molecules generated in the citric acid cycle.

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85
Q

How are NADH and FADH2 utilized in the cell?

A

NADH and FADH2 are utilized to produce ATP, which is the cell’s primary energy source.

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86
Q

Why is the condensation of Acetyl-CoA and oxaloacetate a significant step?

A

It marks the start of the citric acid cycle and initiates the production of energy in the cell.

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87
Q

What is the process called when oxaloacetate binds to the citrate synthase enzyme?

A

The process is called “induced fit.”

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88
Q

What happens during the induced fit process?

A

During induced fit, there is a conformational change or a change in shape of the enzyme.

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89
Q

Why is the conformational change important in the citrate synthase enzyme?

A

The conformational change prevents the unnecessary hydrolysis of the thioester bond in acetyl-CoA.

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90
Q

How many subunits does the citrate synthase enzyme have?

A

The citrate synthase enzyme has two identical subunits.

91
Q

What is the role of the flexible domain in the citrate synthase enzyme?

A

The flexible domain in one of the subunits adapts its conformation when oxaloacetate binds, creating an active site for binding acetyl-CoA.

92
Q

Why is the induced fit model important in citrate synthase?

A

The induced fit model ensures that acetyl-CoA is not hydrolyzed prematurely, preserving the energy stored in the thioester bond.

93
Q

What does the induced fit model guarantee in the citrate synthase reaction?

A

The induced fit model guarantees that acetyl-CoA is used for the intended reaction and not hydrolyzed by mistake.

94
Q

What is the first reaction of the citric acid cycle?

A

The first reaction of the citric acid cycle involves the condensation of acetyl-CoA and oxaloacetate.

95
Q

Which enzyme catalyzes the first reaction of the citric acid cycle?

A

The enzyme citrate synthase catalyzes the first reaction of the citric acid cycle.

96
Q

What type of bond is formed in the first reaction of the citric acid cycle?

A

The first reaction of the citric acid cycle forms a carbon-carbon (C-C) bond.

97
Q

What is the role of acid/base catalysis in the first reaction of the citric acid cycle?

A

Acid/base catalysis facilitates the reaction by molecules acting as either acids or bases.

98
Q

Which group in oxaloacetate acts as an electrophile in the first reaction?

A

The carbonyl group of oxaloacetate acts as an electrophile.

99
Q

Why is the methyl group of acetyl-CoA not reactive initially?

A

The methyl group of acetyl-CoA is not a good nucleophile and is not readily reactive.

100
Q

What activates the methyl group of acetyl-CoA to act as a nucleophile?

A

Deprotonation or loss of a proton activates the methyl group of acetyl-CoA to act as a nucleophile.

101
Q

What is the rate-limiting step of the citric acid cycle?

A

The first reaction, catalyzed by citrate synthase, is the rate-limiting step of the citric acid cycle.

102
Q

What determines the activity of citrate synthase?

A

The activity of citrate synthase is largely dependent on the availability of oxaloacetate, which is required for the reaction to occur.

103
Q

Is the first reaction of the citric acid cycle reversible?

A

No, the first reaction of the citric acid cycle is considered irreversible.

104
Q

How is the activity of citrate synthase regulated?

A

The activity of citrate synthase is regulated by the availability of its substrates (acetyl-CoA and oxaloacetate) and by product inhibition, where the end products of the reaction can inhibit the enzyme’s activity.

105
Q

What occurs in step 2 of the citric acid cycle?

A

Step 2 involves the formation of an isomer through a process of dehydration and rehydration.

106
Q

What is the name of the molecule formed in the first step of this process?

A

The molecule formed in the first step is called cis-aconitate.

107
Q

What enzyme facilitates the dehydration reaction in step 2?

A

The enzyme aconitase facilitates the dehydration reaction.

108
Q

What is the name of the isomer formed in the second step?

A

The isomer formed in the second step is called isocitrate.

109
Q

Which enzyme catalyzes the rehydration reaction in step 2?

A

Aconitase also catalyzes the rehydration reaction in step 2.

110
Q

Why is the formation of isocitrate important in the citric acid cycle?

A

The formation of isocitrate prepares the molecule for further reactions that produce energy-rich molecules like NADH and ATP.

111
Q

What role does aconitase play in step 2 of the citric acid cycle?

A

Aconitase plays a crucial role in facilitating the dehydration and rehydration reactions in step 2.

112
Q

What is the significance of step 2 in the citric acid cycle?

A

Step 2 serves as a transition point in the cycle and sets the stage for the production of energy-carrying molecules.

113
Q

What is the enzyme responsible for facilitating step 3 of the citric acid cycle?

A

Isocitrate dehydrogenase is the enzyme responsible for facilitating step 3.

114
Q

What happens to isocitrate during step 3?

A

Isocitrate undergoes oxidative decarboxylation, resulting in the formation of alpha-ketoglutarate.

115
Q

What is decarboxylation?

A

Decarboxylation is the removal of a carbon dioxide (CO2) molecule from a compound.

116
Q

What occurs simultaneously with decarboxylation during step 3?

A

Simultaneously with decarboxylation, electrons are transferred to NAD+, forming NADH.

117
Q

Why is the transformation of isocitrate into alpha-ketoglutarate important?

A

The transformation of isocitrate into alpha-ketoglutarate prepares the molecule for subsequent reactions in the citric acid cycle.

118
Q

What are the products of step 3?

A

The products of step 3 are alpha-ketoglutarate and NADH.

119
Q

What are the functions of NADH and ATP?

A

NADH and ATP serve as energy-rich molecules that are crucial for various cellular processes and serve as a fundamental source of cellular energy.

120
Q

What is the significance of step 3 in the citric acid cycle?

A

Step 3 is essential for energy production, as it generates NADH and prepares the molecule for further reactions in the cycle.

121
Q

What is the enzyme responsible for facilitating step 4 of the citric acid cycle?

A

Alpha-ketoglutarate dehydrogenase is the enzyme responsible for facilitating step 4.

122
Q

What happens to alpha-ketoglutarate during step 4?

A

Alpha-ketoglutarate undergoes oxidative decarboxylation, resulting in the formation of succinyl-CoA.

123
Q

What is decarboxylation?

A

Decarboxylation is the removal of a carbon dioxide (CO2) molecule from a compound.

124
Q

What occurs simultaneously with decarboxylation during step 4?

A

Simultaneously with decarboxylation, electrons are transferred to NAD+, forming NADH.

125
Q

Why is the transformation of alpha-ketoglutarate into succinyl-CoA important?

A

The transformation of alpha-ketoglutarate into succinyl-CoA is important for subsequent reactions in the citric acid cycle.

126
Q

What are the products of step 4?

A

The products of step 4 are succinyl-CoA and NADH.

127
Q

What are the functions of NADH and ATP?

A

NADH and ATP serve as energy-rich molecules that are crucial for various cellular processes and serve as a fundamental source of cellular energy.

128
Q

What is the significance of step 4 in the citric acid cycle?

A

Step 4 is essential for energy production, as it generates NADH and prepares the molecule for further reactions in the cycle.

129
Q

How does the α-Ketoglutarate Dehydrogenase complex compare to the pyruvate dehydrogenase complex?

A

The α-Ketoglutarate Dehydrogenase complex is similar to the pyruvate dehydrogenase complex in terms of their coenzymes, mechanisms, and functions. However, their active sites differ to accommodate different-sized substances.

130
Q

What is the role of the α-Ketoglutarate Dehydrogenase complex in the breakdown of amino acids?

A

The α-Ketoglutarate Dehydrogenase complex is involved in the breakdown of specific branched amino acids, such as isoleucine, leucine, and valine.

131
Q

What is the function of the third enzyme in the α-Ketoglutarate Dehydrogenase complex?

A

The third enzyme is responsible for lipoate reoxidation and disulfide bridge reformulation, and it is identical in all corresponding enzyme complexes.

132
Q

Which cofactors are required for the α-Ketoglutarate Dehydrogenase complex to carry out its reaction?

A

The α-Ketoglutarate Dehydrogenase complex requires five different cofactors: vitamin B1, B2, B3, B5, and lipoate.

133
Q

How do deficiencies in the required vitamins impact the function of the α-Ketoglutarate Dehydrogenase complex?

A

Deficiencies in the required vitamins, such as vitamin B1 deficiency causing beriberi disease, can affect the function of the α-Ketoglutarate Dehydrogenase complex and the corresponding step in the citric acid cycle.

134
Q

What are the similarities between the α-Ketoglutarate Dehydrogenase complex and the pyruvate dehydrogenase complex?

A

They share the same coenzymes, use identical mechanisms, generate a reducing agent, and produce a product with a high-energy thioester bond.

135
Q

What is the role of alpha-ketoglutarate dehydrogenase in the citric acid cycle?

A

Alpha-ketoglutarate dehydrogenase is responsible for the last oxidative decarboxylation step in the citric acid cycle, where it helps fully oxidize the carbons derived from glucose.

136
Q

Where do the carbons lost in the last oxidative decarboxylation step come from?

A

The carbons lost in this step do not come directly from glucose but rather from the molecule oxaloacetate.

137
Q

What is the product of the alpha-ketoglutarate dehydrogenase reaction?

A

The product of the reaction is succinyl-CoA, which forms another high-energy thioester bond.

138
Q

Is the conversion of alpha-ketoglutarate into succinyl-CoA reversible?

A

No, the conversion is essentially irreversible and highly favorable in terms of thermodynamics.

139
Q

How is the activity of alpha-ketoglutarate dehydrogenase regulated?

A

The activity is regulated through product inhibition, where the accumulation of the product, succinyl-CoA, inhibits the enzyme.

140
Q

What is the purpose of product inhibition in the regulation of alpha-ketoglutarate dehydrogenase?

A

Product inhibition controls the rate of the reaction and ensures that the citric acid cycle proceeds at an appropriate pace.

141
Q

What is the significance of the 5th reaction in the citric acid cycle?

A

The 5th reaction involves substrate-level phosphorylation, which is important for the direct transfer of a high-energy phosphate group to form a high-energy compound.

142
Q

How does the 5th reaction in the citric acid cycle compare to substrate-level phosphorylation in glycolysis?

A

Both involve substrate-level phosphorylation, with the 5th reaction in the citric acid cycle corresponding to reactions 7 and 10 in glycolysis.

143
Q

What is the role of succinyl-CoA synthetase in the 5th reaction?

A

Succinyl-CoA synthetase is the enzyme that catalyzes the substrate-level phosphorylation reaction.

144
Q

What occurs during the hydrolysis of the thioester bond in succinyl-CoA?

A

The hydrolysis releases a large amount of energy, which is used to convert GDP into GTP by adding an inorganic phosphorus group.

145
Q

What is the byproduct released during the 5th reaction?

A

The byproduct released is CoA-SH.

146
Q

What is the importance of GTP formed during the 5th reaction?

A

GTP is an important cofactor and energy donor specifically needed for processes like gluconeogenesis.

147
Q

How are intermediates from the citric acid cycle involved in gluconeogenesis?

A

Intermediates from the citric acid cycle can be used in gluconeogenesis, which is the process of synthesizing glucose from other molecules.

148
Q

What role does succinyl-CoA synthetase play in producing GTP?

A

Succinyl-CoA synthetase plays a role in producing GTP through the substrate-level phosphorylation reaction.

149
Q

How does succinyl-CoA bind to succinyl-CoA synthetase during the reaction?

A

Succinyl-CoA binds to a specific residue called histidine in the enzyme’s active site.

150
Q

What happens in the first step of the reaction catalyzed by succinyl-CoA synthetase?

A

The energy from the thioester bond is used to incorporate a phosphate group into the structure of succinyl-CoA, creating an intermediate.

151
Q

What occurs in the second step of the succinyl-CoA synthetase reaction?

A

The succinate molecule is removed, and the phosphate group binds to an amino acid side chain of the enzyme, forming a phospho-enzyme intermediate.

152
Q

How is GTP formed in the final step of the succinyl-CoA synthetase reaction?

A

The GDP molecule picks up the phosphate group from the enzyme, forming GTP through substrate-level phosphorylation.

153
Q

How is the production of GTP in succinyl-CoA synthetase different from the process that forms ATP in the electron transport chain?

A

The phosphate group is initially bound to succinyl-CoA itself and then transferred to the enzyme’s active site before GTP is formed.

154
Q

Can GTP be converted into ATP, and vice versa? How does this conversion occur?

A

Yes, GTP can be converted into ATP through a transfer to ADP. This conversion is energy-neutral and can happen in both directions: GTP + ATP ⇔ ATP + GDP.

155
Q

Why is GTP production in succinyl-CoA synthetase important for glucose synthesis through gluconeogenesis?

A

GTP is used in the synthesis of glucose through gluconeogenesis, which is the process of forming glucose from non-carbohydrate precursors.

156
Q

What is the role of succinyl-CoA synthetase in step 5 of the citric acid cycle?

A

Succinyl-CoA synthetase facilitates substrate-level phosphorylation in step 5 of the citric acid cycle.

157
Q

What happens in step 5 of the citric acid cycle?

A

In step 5, succinyl-CoA is converted into succinate while also producing ATP through substrate-level phosphorylation.

158
Q

What is substrate-level phosphorylation?

A

Substrate-level phosphorylation is a process where a phosphate group is directly transferred from a substrate molecule (succinyl-CoA) to ADP, forming ATP.

159
Q

What is the function of succinyl-CoA synthetase in this step?

A

Succinyl-CoA synthetase is responsible for facilitating the transfer of the energy stored in the chemical bonds of succinyl-CoA to ADP, resulting in the synthesis of ATP.

160
Q

What does the term “synthetase” indicate about the enzyme succinyl-CoA synthetase?

A

The term “synthetase” indicates that the enzyme helps synthesize or create a new molecule, in this case, ATP.

161
Q

What is the significance of step 5 in the citric acid cycle?

A

Step 5 generates a small amount of ATP directly within the citric acid cycle, providing a source of energy for cellular processes.

162
Q

What is the enzyme responsible for the oxidation of succinate in the sixth step of the citric acid cycle?

A

Succinate dehydrogenase is the enzyme responsible for the oxidation of succinate in the sixth step of the citric acid cycle.

163
Q

What is the product of the oxidation of succinate?

A

The oxidation of succinate results in the conversion of succinate into fumarate.

164
Q

What happens to the hydrogen atoms from succinate during the oxidation process?

A

Two hydrogen atoms from succinate are transferred to FAD, resulting in the formation of the reducing cofactor FADH2.

165
Q

How is succinate dehydrogenase related to the electron transport chain?

A

Succinate dehydrogenase not only participates in the citric acid cycle but also serves as the second complex of the electron transport chain. It acts as a bridge between the two processes.

166
Q

What role does FAD play in succinate dehydrogenase?

A

FAD serves as a prosthetic group that is bound to the succinate dehydrogenase enzyme. It is involved in the transfer of electrons during the oxidation of succinate.

167
Q

What facilitates the transfer of electrons from succinate dehydrogenase to the electron transport chain?

A

Iron-sulfur clusters present in the succinate dehydrogenase enzyme complex facilitate the efficient transfer of electrons to the electron transport chain.

168
Q

What is the enzyme responsible for the hydration across a double bond in step 7 of the citric acid cycle?

A

Fumarase is the enzyme responsible for the hydration across a double bond in step 7 of the citric acid cycle.

169
Q

What is the result of the hydration reaction catalyzed by fumarase?

A

The result of the hydration reaction is the formation of L-Malate from fumarate.

170
Q

How does fumarase add water molecules to fumarate?

A

Fumarase adds the hydroxyl group and the hydrogen ion (proton) separately to fumarate during the hydration reaction.

171
Q

What is the term used to describe the specificity of fumarase in creating a particular form of the resulting compound?

A

Fumarase is highly stereospecific, meaning it creates only one specific form of the resulting compound, which is L-Malate.

172
Q

What is the purpose of adding the hydroxyl group and the hydrogen ion separately in the hydration reaction?

A

Adding the hydroxyl group and the hydrogen ion separately allows the formation of a temporary carbanion transition state, enabling stable positions for all carbon atoms with four covalent bonds each.

173
Q

How does step 7 of the citric acid cycle contribute to the overall cycle?

A

Step 7, through the hydration reaction catalyzed by fumarase, helps in restoring the initial compound, oxaloacetate, which is where the citric acid cycle begins. Each step of the cycle brings us closer to replenishing the starting compound and continuing the cycle.

174
Q

What is the enzyme responsible for the final reaction in the citric acid cycle?

A

Malate dehydrogenase is the enzyme responsible for the final reaction in the citric acid cycle.

175
Q

What is the purpose of step 8 in the citric acid cycle?

A

Step 8 involves the oxidation of an alcohol group and the regeneration of oxaloacetate.

176
Q

What molecule is used as a cofactor by malate dehydrogenase during the reaction?

A

Malate dehydrogenase uses NAD+ as a cofactor during the reaction.

177
Q

What is the role of NAD+ in the reaction catalyzed by malate dehydrogenase?

A

NAD+ oxidizes the hydroxyl group, converting it into a ketone group.

178
Q

Is the final step of the citric acid cycle thermodynamically favorable or unfavorable?

A

The final step of the citric acid cycle is thermodynamically unfavorable, requiring an input of energy.

179
Q

How is equilibrium maintained in the conversion of L-malate into oxaloacetate despite the unfavorable deltaG value?

A

The concentration of oxaloacetate is kept extremely low in the cell, which helps maintain equilibrium and allows the conversion to proceed.

180
Q

What is the significance of regulating the concentration of oxaloacetate in the citric acid cycle?

A

By regulating the concentration of oxaloacetate and ensuring its scarcity, the citric acid cycle can continue efficiently, completing its cycle and producing energy-rich molecules for cellular processes.

181
Q

Why is the regulation of the citric acid cycle important?

A

The regulation of the citric acid cycle is important because it generates a significant amount of energy for the cell and helps maintain stable energy levels required for cell survival and various cellular processes.

182
Q

What are the three main regulatory points at the beginning of the citric acid cycle?

A

The three main regulatory points at the beginning of the citric acid cycle are activation by substrate availability, inhibition by product accumulation, and allosteric regulation by reducing cofactors and ATP.

183
Q

How does activation by substrate availability regulate the citric acid cycle?

A

The cycle can be activated by the availability of the substrate, such as pyruvate, and its conversion to Acetyl-CoA, which initiates the cycle.

184
Q

How does inhibition by product accumulation regulate the citric acid cycle?

A

The cycle can be inhibited by the accumulation of certain intermediate products. For example, succinyl-CoA can negatively regulate the alpha-ketoglutarate dehydrogenase complex and citrate synthase by binding to their allosteric sites.

185
Q

How does allosteric regulation by reducing cofactors and ATP regulate the citric acid cycle?

A

The total amount of reducing cofactors (such as NADH+H+) and ATP available inside the cell can also regulate the cycle.

186
Q

What is depicted in the diagram of the citric acid cycle?

A

The diagram depicts all the allosteric regulators of the citric acid cycle.

187
Q

How can succinyl-CoA inhibit the citric acid cycle?

A

Succinyl-CoA can inhibit both the alpha-ketoglutarate dehydrogenase complex and citrate synthase by binding to their allosteric sites.

188
Q

What role do reduced cofactors and high concentrations of ATP play in regulating the citric acid cycle?

A

Accumulation of reduced cofactors or high concentrations of ATP can act as inhibitors of the citric acid cycle.

189
Q

How can the availability of fatty acids influence the citric acid cycle?

A

The availability of fatty acids as an energy source can reduce the use of pyruvate for Acetyl-CoA formation, thus inhibiting the first step of the citric acid cycle.

190
Q

How does calcium act as an activator of the citric acid cycle?

A

Calcium, released from the endoplasmic reticulum, can act as an activator of the citric acid cycle, particularly in muscle cells, where it stimulates energy production to sustain muscle contractions.

191
Q

How can the citric acid cycle be activated?

A

The citric acid cycle can be activated by the starting molecule acetyl-CoA as well as by the breakdown of certain amino acids.

192
Q

Which amino acids can be converted into alpha-ketoglutarate?

A

Glutamate, glutamine, arginine, histidine, and proline can be converted into alpha-ketoglutarate.

193
Q

Which amino acids can be converted into succinyl-CoA?

A

Isoleucine, methionine, threonine, and valine can be converted into succinyl-CoA through oxidation.

194
Q

How do amino acids contribute to the citric acid cycle?

A

Amino acids contribute to the citric acid cycle by supplying alpha-ketoglutarate and succinyl-CoA.

195
Q

How does the increase in succinyl-CoA concentration affect the citric acid cycle?

A

The increase in succinyl-CoA concentration inhibits the first step of the citric acid cycle and prevents the use of pyruvate for activating the cycle.

196
Q

What is the role of citrate in inhibiting glycolysis?

A

Citrate, a molecule produced in the citric acid cycle, inhibits the enzyme phosphofructokinase, which is involved in the third reaction of glycolysis.

197
Q

How does citrate affect glycolysis if it is produced in the mitochondrial matrix?

A

When there is an abundance of energy and ATP levels increase, isocitrate dehydrogenase, an enzyme involved in the citric acid cycle, is inhibited. This leads to the accumulation of isocitrate, which can be reversed to form citrate. Citrate is then transported into the cytosol, where it inhibits phosphofructokinase-1, preventing the breakdown of additional glucose molecules.

198
Q

What is the consequence of citrate inhibiting glycolysis?

A

Citrate inhibiting glycolysis allows the cell to primarily use amino acids as an energy resource and affects glucose metabolism.

199
Q

How does the breakdown of amino acids and the citric acid cycle interplay with other metabolic pathways?

A

The breakdown of amino acids and the citric acid cycle interplay by allowing the switching of energy sources and integration with other metabolic pathways.

200
Q

What is the additional layer of regulation in the citric acid cycle besides allosteric regulation?

A

The additional layer of regulation is covalent modification through reversible phosphorylation of the pyruvate dehydrogenase complex.

201
Q

What enzyme is responsible for phosphorylating the pyruvate dehydrogenase complex?

A

The enzyme pyruvate dehydrogenase kinase phosphorylates the pyruvate dehydrogenase complex.

202
Q

What happens when the pyruvate dehydrogenase complex is phosphorylated?

A

Phosphorylation of the pyruvate dehydrogenase complex by pyruvate dehydrogenase kinase leads to its inactivation.

203
Q

What factors regulate the activity of pyruvate dehydrogenase kinase?

A

High concentrations of NADH+H+, ATP, and Acetyl-CoA regulate the activity of pyruvate dehydrogenase kinase.

204
Q

What conditions inhibit the pyruvate dehydrogenase complex?

A

A high concentration of pyruvate and abundant cofactors such as NAD+, ADP, CoASH, and Ca2+ inhibit the pyruvate dehydrogenase complex.

205
Q

How is the pyruvate dehydrogenase complex reactivated?

A

The part of the complex called pyruvate dehydrogenase phosphatase removes the phosphate groups, reactivating the pyruvate dehydrogenase complex.

206
Q

What are the major allosteric regulators for pyruvate dehydrogenase complex?

A

The major allosteric regulators for pyruvate dehydrogenase complex are ATP, Acetyl-CoA, NADH, fatty acids, AMP, CoA, NAD+, and Ca2+.

207
Q

How do the allosteric regulators influence the activity of the pyruvate dehydrogenase complex?

A

The allosteric regulators can bind to specific sites on the pyruvate dehydrogenase complex and either activate or inhibit the enzyme.

208
Q

What does the regulation of the citric acid cycle through allosteric regulation and reversible phosphorylation demonstrate?

A

The regulation of the citric acid cycle through both allosteric regulation and reversible phosphorylation highlights the complex mechanism involved in controlling this key reaction in cellular metabolism.

209
Q

How rare are mutations in the enzymes of the citric acid cycle?

A

Mutations in the enzymes of the citric acid cycle are generally very rare.

210
Q

Which specific enzyme in the citric acid cycle can have genetic mutations?

A

Isocitrate dehydrogenase is an enzyme in the citric acid cycle that can have genetic mutations.

211
Q

What happens when isocitrate dehydrogenase has a mutation?

A

A mutation in isocitrate dehydrogenase can result in a mutant enzyme that converts alpha-ketoglutarate into two hydroxyglutarate instead of converting isocitrate into alpha-ketoglutarate.

212
Q

Why does the presence of two hydroxyglutarate become problematic?

A

Two hydroxyglutarate competes with alpha-ketoglutarate for the regulation of histone demethylation, disrupting the normal epigenetic processes and potentially leading to the development of cancer.

213
Q

In which types of tumors are these mechanisms and effects particularly observed?

A

These mechanisms and effects are particularly observed in brain tumors and gliomas.

214
Q

What is the normal function of alpha-ketoglutarate in histone demethylation?

A

Alpha-ketoglutarate acts as a signaling molecule and regulator of histone demethylation.

215
Q

How does the presence of two hydroxyglutarate affect histone demethylation?

A

Two hydroxyglutarate acts as a competitive inhibitor for alpha-ketoglutarate in the regulation of histone demethylation.

216
Q

What are some factors and mechanisms that can contribute to cancer development?

A

Alterations in glycolytic enzymes, specific mutations in citric acid cycle intermediates, and mutations in the pyruvate mitochondrial carrier are some factors and mechanisms that can contribute to cancer development.

217
Q

Why is finding a universal solution to cancer challenging?

A

The complexity of cancer development, involving multiple factors and mechanisms, makes it difficult to find a single effective drug or universal solution to stop it.

218
Q

Where does the citric acid cycle take place?

A

The citric acid cycle takes place in the matrix of mitochondria.

219
Q

What is the main purpose of the citric acid cycle?

A

The main purpose of the citric acid cycle is to serve as a common metabolic pathway for fully oxidizing different nutrients, such as carbohydrates, lipids, and proteins, to produce metabolic energy.

220
Q

What role does the pyruvate dehydrogenase complex play in the citric acid cycle?

A

The pyruvate dehydrogenase complex converts pyruvate, a product of glycolysis, into acetyl-CoA, which enters the citric acid cycle.

221
Q

How is ATP produced in the citric acid cycle?

A

The citric acid cycle generates GTP and reduced cofactors (NADH+H+ and FADH2), which have the potential to yield ATP, the energy currency of cells.

222
Q

How is the citric acid cycle regulated?

A

The citric acid cycle is regulated based on the availability of substrates and product inhibition. High levels of NADH+H+ and ATP act as feedback signals to inhibit the cycle and prevent excessive energy production.

223
Q

What cofactors are required for the function of the citric acid cycle?

A

The oxidative decarboxylation reactions and overall function of the citric acid cycle require specific cofactors, including thiamine, riboflavin, niacin, pantothenic acid, and lipoate.

224
Q

What recent advancements have been made regarding the citric acid cycle?

A

Recent advancements suggest that enzymes within the citric acid cycle may form clusters through non-covalent bonds, enhancing the speed and effectiveness of the cycle by facilitating the efficient transmission of substrates between enzymes.

biochem sem 2 (7 decks)

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