Metabolism

Question 1

Define:

metabolism

Answer 1

It collectively refers to the biological processes that occur within cells.

Specifically, these processes either generate energy through the breakdown of molecules or use energy to build molecules.

Metabolism is also known as “cellular respiration.”

Question 2

Define:

catabolism

Answer 2

It is the biological breakdown of molecules into smaller units.

Catabolic processes are accompanied by the generation of energy.

The opposite of this class of metabolic reactions is anabolism.

Question 3

Define:

anabolism

Answer 3

It is the creation of larger biomolecules from smaller units.

Anabolic processes require energy input.

The opposite of this class of metabolic reactions is catabolism.

Question 4

What broad distinction separates aerobic and anaerobic respiration?

Answer 4

• Aerobic respiration requires oxygen
• Anaerobic respiration occurs in the absence of oxygen.

As part of metabolism, both processes involve the breakdown of biological molecules and the eventual release of energy.

Question 5

What is the chemical formula of glucose?

Answer 5

C₆H₁₂O₆

Broadly, glucose is a carbohydrate; specifically, it is a monosaccharide.

Question 6

The majority of glucose molecules enter the cell via which transport method?

Answer 6

facilitated diffusion

This occurs with the assistance of a family of transport proteins, GLUT 1-4.

This process is promoted by high plasma glucose levels, which creates a concentration gradient that drives glucose into the cells. It is also promoted by the activity of insulin, which increases the number of GLUT 4 transporters on the membranes of certain cell types.

Question 7

In eukaryotes, which metabolic process occurs in the cytosol regardless of the presence or absence of oxygen?

Answer 7

Glycolysis occurs anaerobically in the cytosol.

Glycolysis is a biochemical process that forms pyruvate from the breakdown of glucose. The pathway produces 2 NADH and a net total of 2 ATP per glucose molecule.

Question 8

Fill in the blank.

In prokaryotes, glycolysis occurs in the _______.

Answer 8

cytosol

Glycolysis occurs in the cytoplasm for all cells, whether prokaryotic or eukaryotic. (Even if you didn’t know this, you should absolutely know that prokaryotic cells lack membrane-bound organelles, meaning that metabolic processes generally occur in the cytoplasm.)

Question 9

Describe the net reaction of glycolysis.

Answer 9

C₆H₁₂O₆ + 2 NAD⁺ + 2 P_i + 2 ADP → 2 pyruvate + 2 ATP + 2 NADH + 2 H₂O + 2 H⁺

While glycolysis only produces a net of two ATP molecules, it generates a total of four. The other two molecules of ATP are used as reactants in early glycolytic steps.

Question 10

Fill in the blank.

Glucose contains ________ carbons, while pyruvate contains ________ carbons.

Answer 10

six, three

As such, complete glycolysis of a single glucose molecules produces two pyruvate molecules for use in later metabolic processes.

Question 11

In the net reaction of glycolysis, for every pyruvate molecule that is produced, how many ADP molecules are consumed?

Answer 11

one

You should know the net reaction of glycolysis inside and out! When one glucose molecule undergoes glycolysis, it consumes a net of two ADP molecules and produces two pyruvate molecules. Thus, the ratio of pyruvate to ADP is 1:1.

Question 12

If six glucose molecules underwent complete glycolysis, how many molecules of NADH would be produced?

Answer 12

12

Per the net reaction of glycolysis, for every glucose molecule consumed, two molecules of NADH are produced. Thus, complete glycolysis of six glucose molecules would produce 12 NADH.

Question 13

In the complete glycolysis of a single glucose molecule, how many carbon atoms are lost as carbon dioxide?

Answer 13

zero

Glycolysis does not produce carbon dioxide (CO₂)! Instead, all of the carbon atoms in glucose end up in pyruvate.

In contrast, other metabolic processes do yield CO₂, most notably the Krebs cycle.

Question 14

Glucose enters the cells through a family of GLUT transporters. What process ensures that glucose does not exit by a similar mechanism?

Answer 14

In the first step of glycolysis, glucose is converted to glucose 6-phosphate (G6P). Since GLUT transporters only facilitate the movement of glucose, G6P cannot utilize them to leave the cell.

Additionally, since G6P is very negative, it is even more incapable than glucose of exiting directly through the hydrophobic cell membrane.

Question 15

In the first step of glycolysis, glucose is converted to glucose 6-phosphate (G6P). What enzyme catalyzes this reaction?

Answer 15

hexokinase

Remember, kinases are a class of enzymes that phosphorylate other molecules. You can use the name “hexokinase” to predict this molecule’s role: it is a kinase that phosphorylates hexoses.

Question 16

Which reaction is the rate-limiting step of glycolysis?

Answer 16

Step 3 involves the phosphorylation of fructose 6-phosphate to form fructose 1,6-bisphosphate.

This reaction is catalyzed by the enzyme phosphofructokinase-1 (PFK-1). For this reason, PFK-1 is sometimes called the rate-limiting enzyme of glycolysis.

Question 17

Step 2 of glycolysis involves the conversion of glucose 6-phosphate to fructose 6-phosphate. The enzyme that catalyzes this reaction falls into which of the six main classes of enzymes?

Answer 17

isomerase

You should know that glucose and fructose are isomers, so glucose 6-phosphate and fructose 6-phosphate are isomers as well! Isomers are interconverted by isomerase enzymes. Specifically, the enzyme that catalyzes this reaction is phosphoglucose isomerase.

Question 18

The enzyme that catalyzes step 10 of glycolysis falls into which of the six main classes of enzymes?

Answer 18

transferase

Specifically, this enzyme is pyruvate kinase (a kinase is a type of transferase). Pyruvate kinase catalyzes the conversion of phosphoenolpyruvate into pyruvate, a reaction that also produces ATP from ADP.

Question 19

In which step of glycolysis does the six-carbon substrate split into two three-carbon molecules, and which enzyme catalyzes this step?

Answer 19

Step 4 of glycolysis, which is catalyzed by aldolase.

From this point onward, you should imagine twice the substrate molecules at play (since one glucose substrate has been transformed into two 3-carbon substrates).

Question 20

Name the two 3-carbon molecules that are produced in step 4 of glycolysis.

Answer 20

1. Glyceraldehyde 3-phosphate
2. Dihydroxyacetone phosphate

The production of these molecules is catalyzed by the enzyme aldolase.

Question 21

By step number (for example, “step 1”), which steps of glycolysis are irreversible?

Answer 21

Steps 1, 3, and 10

This means that these steps are so highly exergonic that they cannot effectively be reversed. The remaining seven steps of glycolysis are reversible.

Question 22

Which glycolytic enzymes catalyze irreversible steps?

Hint: There are three of them.

Answer 22

• Hexokinase (or glucokinase)
• Phosphofructokinase-1 (PFK-1)
• Pyruvate kinase

Hexokinase and glucokinase catalyze step 1 of glycolysis. PFK-1 catalyzes step 3, and pyruvate kinase catalyzes the final step (step 10).

Question 23

True or false.

The seven reversible steps of glycolysis are reversible because they are highly endergonic.

Answer 23

False

While irreversible steps are irreversible because they are highly exergonic, reversible steps are not highly endergonic (nonspontaneous). Instead, they tend to have ΔG values that are close to 0.

Question 24

Which step(s) of glycolysis require(s) the input of ATP?

Answer 24

Steps 1 and 3

Predictably, both of these steps involve the phosphorylation of the substrate. In step 1, glucose is converted into glucose 6-phosphate, while in step 3, fructose 6-phosphate is converted into fructose 1,6-bisphosphate.

Question 25

Which **step(s) of glycolysis** produce(s) ATP?

Answer 25

Steps 7 and 10 ## Footnote Both of these steps involve the substrate losing a phosphate group, which is then added to ADP to create ATP. In step 7, 1,3-bisphosphoglycerate is dephosphorylated to form 3-phosphoglycerate. In step 10, phosphoenolpyruvate is converted to pyruvate.

Question 26

Which **step(s) of glycolysis** produce(s) NADH?

Answer 26

Step 6 ## Footnote This step is catalyzed by glyceraldehyde 3-phosphate dehydrogenase, or GAPDH. The "dehydrogenase" in its name indicates that it is an oxidoreductase enzyme, and in fact, it catalyzes the reduction of NAD⁺ to NADH.

Question 27

Of AMP, ATP, and citrate, which is most likely to serve as an **allosteric activator of PFK-1**?

Answer 27

AMP ## Footnote The other two molecules are inhibitors. You can figure this out logically: glycolysis should be stimulated when available energy is low (to make more) and inhibited when it is high. High AMP concentrations imply that cellular ATP is low.

Question 28

Which **glycolytic intermediate** is most involved in the substrate-level phosphorylation that produces ATP?

Answer 28

**1,3-bisphosphoglycerate** serves as the "substrate" in this form of phosphorylation. Specifically, it provides the phosphate group that is transferred to ADP, forming ATP. ## Footnote The other common form of phosphorylation is oxidative phosphorylation, which takes place immediately after the electron transport chain.

Question 29

Apart from hexokinase, what enzyme phosphorylates glucose into **glucose 6-phosphate**?

Answer 29

glucokinase ## Footnote It catalyzes the same reaction as hexokinase, but it does so under different conditions and with different kinetic parameters. This helps the body fine-tune glucose metabolism.

Question 30

Describe the **difference** between hexokinase and glucokinase with regard to the tissues in which they are found.

Answer 30

* Hexokinase is found in **most body tissues**. * Glucokinase is selectively present only in **pancreatic beta cells** and in the **liver**.

Question 31

# Fill in the blank. Compared to hexokinase, glucokinase has a \_\_\_\_\_\_\_ K_m and a \_\_\_\_\_\_\_ V_max.

Answer 31

higher, higher ## Footnote This means that glucokinase requires more substrate (glucose) to reach half of its maximum reaction velocity, but that velocity, once reached, is higher than that of the reaction catalyzed by hexokinase.

Question 32

Between hexokinase and glucokinase, which enzyme has a **lower affinity** for glucose?

Answer 32

glucokinase ## Footnote Recall that K_m is inversely proportional to enzyme-substrate affinity. Since the reaction catalyzed by glucokinase has a higher K_m than that catalyzed by hexokinase, glucokinase has a *lower* affinity for its substrate than does hexokinase.

Question 33

Between hexokinase and glucokinase, which enzyme is **inhibited** by its product (glucose 6-phosphate)?

Answer 33

hexokinase ## Footnote This means that hexokinase is highly subject to negative feedback. Once it produces sufficient G6P, the reaction slows.

Question 34

The activity of glucokinase is intricately tied to the **release and function** of which hormone?

Answer 34

insulin ## Footnote You may have guessed this based on the fact that glucokinase is located in pancreatic beta cells, which are the cells that produce insulin in the human body. Glucokinase is stimulated by insulin, and it is also involved in the regulation of insulin secretion.

Question 35

The first reaction of both **glycolysis and glycogen synthesis** involves the **conversion** of glucose into what product?

Answer 35

Glucose 6-phosphate | (G6P) ## Footnote In glycolysis, glucose is typically transformed into G6P by the enzyme hexokinase. In glycogen synthesis, the same reaction occurs, but it is generally catalyzed by glucokinase.

Question 36

# Fill in the blank. Taken together, all of the parameters of glucokinase ensure that when glucose concentration is very high, glucose is store in the \_\_\_\_\_\_\_\_\_\_\_.

Answer 36

liver ## Footnote The differences between glucokinase and hexokinase make much more sense with this function in mind. When glucose concentration is high, insulin is released, stimulating glucokinase to produce G6P in the liver, where it can be used for glycogen synthesis. In contrast, most tissues of the body do not need any more G6P than usual, so negative feedback ensures that *hexokinase* does not produce too much G6P for use in glycolysis.

Question 37

Which metabolic process immediately **follows glycolysis** in oxygen-poor conditions?

Answer 37

**Fermentation** occurs after glycolysis in anaerobic conditions. This process takes place when O₂ is too scarce to facilitate the entry of glycolytic products into the Krebs cycle. ## Footnote This can produce either ethanol or lactic acid, depending on the species.

Question 38

The conversion of pyruvate to lactic acid, often referred to simply as "fermentation," produces no ATP. However, it is still necessary in anaerobic conditions. What **purpose** does this process serve?

Answer 38

Fermentation **regenerates NAD⁺** by oxidizing NADH and reducing pyruvate. ## Footnote NAD⁺ is necessary for glycolysis, but cannot be regenerated by the electron transport chain under anaerobic conditions. Fermentation serves to produce NAD⁺, reducing NADH buildup and allowing glycolysis to continue.

Question 39

Which **two molecules** can be created by the fermentation of pyruvate?

Answer 39

* Ethanol * Lactate ## Footnote Alcohol fermentation, which takes place in yeast and certain bacteria, involves the reduction of pyruvate to ethanol. Lactic acid fermentation, which takes place in human muscle cells as part of anaerobic respiration, involves the reduction of pyruvate to lactate.

Question 40

In humans, what enzyme catalyzes **fermentation**?

Answer 40

lactate dehydrogenase ## Footnote In humans (and mammals in general), fermentation is specifically *lactic acid* fermentation, which involves the reduction of pyruvate to lactate. This reaction is catalyzed by lactate dehydrogenase.

Question 41

Which **metabolic process** immediately follows glycolysis and produces acetyl-CoA?

Answer 41

**Pyruvate decarboxylation** occurs between glycolysis and the Krebs cycle. This process takes place in the **mitochondrial matrix**. ## Footnote Under aerobic conditions, pyruvate (a three-carbon molecule) is converted to a two-carbon acetyl group. This group then attaches to coenzyme A.

Question 42

Glycolysis occurs in the cytosol, while pyruvate decarboxylation occurs in the mitochondrial matrix. What **method of membrane transport** moves pyruvate between these locations?

Answer 42

active transport ## Footnote Pyruvate is a negatively-charged molecule and therefore cannot passively diffuse across cell membranes. Additionally, its unfavorable concentration gradient prevents it from moving via facilitated diffusion. Instead, it is transported actively by an enzyme termed pyruvate translocase.

Question 43

What broad name is given to the set of enzymes that catalyze **pyruvate decarboxylation**?

Answer 43

pyruvate dehydrogenase complex | (PDH) ## Footnote The PDH is actually a set of three enzymes that work in concert to convert pyruvate into acetyl-CoA, producing NADH in the process.

Question 44

What are the **substrates and products** of pyruvate decarboxylation?

Answer 44

* **Pyruvate**, a three-carbon molecule, is the substrate. * **CO₂**, **NADH**, and **acetyl-CoA** are the ultimate products.

Question 45

Is pyruvate decarboxylation a **redox reaction**?

Answer 45

yes ## Footnote Pyruvate decarboxylation is an oxidation-reduction (redox) reaction. This should be clear both because pyruvate decarboxylation produces NADH from NAD⁺ (an example of reduction) and because it is catalyzed by a dehydrogenase enzyme complex. When you see "dehydrogenase," think "redox reaction!"

Question 46

Name at least **two cellular conditions** that inhibit pyruvate decarboxylation.

Answer 46

* Increased [acetyl-CoA] * Increased [ATP] * Increased [NADH] ## Footnote Acetyl-CoA and NADH are products of pyruvate decarboxylation, so they inhibit this process via straightforward negative feedback. High [ATP] is indicative of abundant energy in the cell, meaning that pyruvate decarboxylation is not urgently needed.

Question 47

# True or false. All acetyl-CoA that enters the Krebs cycle is generated via pyruvate decarboxylation.

Answer 47

False ## Footnote Be wary of extreme answers like this one! Acetyl-CoA is actually generated via a number of other metabolic pathways, including beta-oxidation of fatty acids and the breakdown of ketogenic amino acids.

Question 48

Two glucose molecules undergo glycolysis, producing pyruvate. How many molecules of **NADH** will be produced simply from the decarboxylation of these products?

Answer 48

four ## Footnote During glycolysis, the initial two glucose molecules will be converted into four molecules of pyruvate. For every molecule of pyruvate that is decarboxylated by pyruvate dehydrogenase, one molecule of NADH is formed.

Question 49

Which metabolic process generates both **NADH** and **FADH**₂?

Answer 49

The **Krebs cycle** produces the electron carriers NADH and FADH₂, as well as an ATP equivalent (either ATP or GTP). ## Footnote The Krebs cycle, also known as the citric acid cycle, involves the cyclic transformation of organic molecules.

Question 50

# True or false. The main, direct purpose of the Krebs cycle is to produce ATP or ATP equivalents.

Answer 50

False ## Footnote The Krebs cycle actually produces very few ATP equivalents (specifically, it only forms 1 GTP in each turn of the cycle). Instead, its main purpose is to reduce large quantities of electron carriers for later use in the electron transport chain.

Question 51

In **eukaryotes**, where does the Krebs cycle occur?

Answer 51

in the mitochondrial matrix ## Footnote You should know that, in eukaryotic cells, glycolysis occurs in the cytosol, the Krebs cycle takes place in the mitochondrial matrix, and the electron transport chain takes place along the inner mitochondrial membrane.

Question 52

In **prokaryotes**, where does the Krebs cycle occur?

Answer 52

in the cytosol ## Footnote In prokaryotes, glycolysis and the Krebs cycle occur in the cytosol, while the electron transport chain takes place along the plasma membrane of the cell.

Question 53

Is oxygen a **reactant** in the Krebs cycle?

Answer 53

no ## Footnote Interestingly, oxygen is not directly involved (as either a reactant or a product) in the Krebs cycle. However, if a cell is starved for oxygen, the cycle will slow to a halt as its products build up and are not used by the electron transport chain.

Question 54

What is the **initial substrate** of the Krebs cycle, and with which **molecule** does it first react?

Answer 54

**Acetyl-CoA**, a two-carbon compound, is the substrate entering the cycle. It immediately reacts with oxaloacetate to form a six-carbon compound. ## Footnote Coenzyme A is released in this process and can be used again.

Question 55

How many molecules of NADH and FADH₂, respectively, are produced during **one turn** of the Krebs cycle?

Answer 55

One full turn produces **3 NADH molecules** and **1 FADH₂**. ## Footnote Other products include carbon dioxide, which is released as waste, and one molecule of GTP.

Question 56

What is the **main waste product** of the Krebs cycle?

Answer 56

carbon dioxide | (CO₂) ## Footnote In fact, the constant production of CO₂ by the Krebs cycle is the main reason why we need to exhale CO₂ during respiration. Specifically, two CO₂ molecules are lost in every full turn of the cycle.

Question 57

What is the **product** of step 1 of the Krebs cycle?

Answer 57

the six-carbon molecule **citrate** ## Footnote The production of citrate from acetyl-CoA, oxaloacetate, and water in this step is catalyzed by the enzyme citrate synthase.

Question 58

# Fill in the blank. In step 2 of the Krebs cycle, citrate is transformed into its isomer, a molecule named \_\_\_\_\_\_\_.

Answer 58

isocitrate ## Footnote Predictably, this reaction is catalyzed by an isomerase! Note also that as isomers, citrate and isocitrate have identical chemical formulas; in particular, both contain six carbon atoms.

Question 59

# Fill in the blank. In step 3 of the Krebs cycle, isocitrate is transformed into \_\_\_\_\_\_\_\_\_\_\_.

Answer 59

α-ketoglutarate ## Footnote This step is catalyzed by isocitrate dehydrogenase and is actually the rate-limiting step of the Krebs cycle. The term "dehydrogenase" tells us that this is also a redox reaction, and in fact, it produces the first NADH of the cycle. Additionally, one molecule of CO₂ is lost.

Question 60

Name the main reactant and the main product of **step 4** of the Krebs cycle.

Answer 60

The main reactant is **α-ketoglutarate**, and the main product is **succinyl-CoA**. ## Footnote α-ketoglutarate is a five-carbon molecule, while succinyl-CoA contains four carbons. This means that a molecule of carbon dioxide is lost during the course of this reaction.

Question 61

In step 5 of the Krebs cycle, a molecule of GTP is formed. The energy to create this GTP molecule came from the breaking of what **high-energy reactant**?

Answer 61

succinyl-CoA ## Footnote It helps to remember that succinyl-CoA is the product of step 4 of the cycle and thus must be the reactant of step 5. It's also helpful to understand that bonds to coenzyme A (CoA) are high-energy (hence the role of acetyl-CoA in our metabolism).

Question 62

Name the main reactant and the main product of **step 6** of the Krebs cycle.

Answer 62

The main reactant is **succinate**, and the main product is **fumarate**. ## Footnote This reaction, which is catalyzed by the enzyme succinate dehydrogenase, also produces one molecule of the reduced electron carrier FADH₂.

Question 63

The enzyme that catalyzes step 6 of the Krebs cycle plays what other **role** in cellular metabolism? ## Footnote Hint: Remember, step 6 is the only step of the Krebs cycle that produces FADH₂.

Answer 63

It acts as **complex II** of the electron transport chain. | (ETC) ## Footnote This is a tough one! However, if you remember that FADH₂ enters the ETC at complex II, you may find it easier to understand that this happens because the enzyme (succinate dehydrogenase) that produces FADH₂ in step 6 of the Krebs cycle *is* complex II of the ETC.

Question 64

# Fill in the blank. In step 7 of the Krebs cycle, ________ is transformed into L-malate by the enzyme \_\_\_\_\_\_\_\_.

Answer 64

fumarate, fumarase ## Footnote Both fumarate and L-malate are four-carbon species.

Question 65

# Fill in the blank. In step 8 of the Krebs cycle, the four-carbon molecule \_\_\_\_\_\_\_\_ is transformed into the four-carbon molecule \_\_\_\_\_\_\_\_.

Answer 65

L-malate, oxaloacetate ## Footnote From here, the cycle can start all over with the combination of oxaloacetate with acetyl-CoA to form citrate.

Question 66

Which step(s) of the Krebs cycle produce(s) **NADH**?

Answer 66

* step 3 * step 4 * step 8 ## Footnote Remember, a total of three NADH molecules (one in each step listed above) are created per turn of the Krebs cycle!

Question 67

Which step(s) of the Krebs cycle produce(s) **FADH**₂?

Answer 67

step 6 ## Footnote This step is catalyzed by succinate dehydrogenase, which is also complex II of the electron transport chain.

Question 68

Which step(s) of the Krebs cycle produce(s) **ATP** or an **ATP equivalent**?

Answer 68

step 5 ## Footnote Step 5 involves the conversion of succinyl-CoA to succinate. The breakage of the thioester bond in succinyl-CoA releases sufficient energy to produce GTP from GDP.

Question 69

Which step of the Krebs cycle is **rate-limiting**?

Answer 69

step 3 | (the conversion of isocitrate into α-ketoglutarate) ## Footnote The rate-limiting step of a process is the slowest step, which by its nature then dictates the rate of the overall process. In the Krebs cycle, that is step 3.

Question 70

In which step of the Krebs cycle does the carbon substrate lose its **first carbon** (to go from six to five carbons)?

Answer 70

step 3 | (the conversion of isocitrate into α-ketoglutarate) ## Footnote This is the first step of the cycle in which carbon dioxide is lost as a waste product.

Question 71

In which step of the Krebs cycle does the carbon substrate lose its **second carbon** (to go from five to four carbons)?

Answer 71

step 4 | (the conversion of α-ketoglutarate into succinyl-CoA) ## Footnote This is the second step of the cycle in which carbon dioxide is lost as a waste product.

Question 72

Name the **three main regulatory** steps of the Krebs cycle (by step number).

Answer 72

1. step 1 2. step 3 3. step 4 ## Footnote These are the three most strongly exergonic (thermodynamically favorable) steps of the cycle. All three are subject to regulation by various molecules.

Question 73

Which **three molecules** exert regulatory effects on step 1 of the Krebs cycle? ## Footnote Remember, this step involves the conversion of oxaloacetate and acetyl-CoA to citrate.

Answer 73

1. ATP 2. NADH 3. Citrate ## Footnote All three of the regulatory steps of the Krebs cycle are actually inhibited by ATP and NADH (which both serve to indicate that the cycle has already produced enough products). In addition, step 1 is inhibited by its own product, citrate.

Question 74

Which step of the Krebs cycle is **inhibited** by its direct product succinyl-CoA as well as by ATP and NADH?

Answer 74

step 4 ## Footnote Step 4 is the step of the Krebs cycle in which succinyl-CoA, a high-energy substrate, is produced. This regulatory step is subject to typical negative feedback.

Question 75

The Krebs cycle would be expected to progress the most quickly under conditions of a [high/low] ADP:ATP ratio and a [high/low] NADH:NAD⁺ ratio. ## Footnote Choose one term from each box below to accurately complete the sentence.

Answer 75

high, low ## Footnote Be sure to read carefully here! The first ratio given is ADP to ATP, so a high ratio indicates relatively less ATP present. The second ratio is NADH to NAD⁺, so a *low* ratio indicates relatively less NADH present.

Question 76

# True or false. Step 3 of the Krebs cycle (the conversion of isocitrate into α-ketoglutarate) is inhibited by its direct product, NADH.

Answer 76

True ## Footnote NADH is indeed a direct product of step 3! In addition, all of the regulatory steps of the Krebs cycle (steps 1, 3, and 4) are inhibited by NADH.

Question 77

In eukaryotes, the **electron transport chain** takes place in which part of the mitochondria? | (ETC)

Answer 77

along the **inner** mitochondrial membrane ## Footnote The ETC can therefore utilize the compartments on either side (the mitochondrial matrix and the intermembrane space) to establish a proton gradient between the two.

Question 78

What is the **main purpose** of the electron transport chain? | (ETC)

Answer 78

It is to **generate** proton-motive force for subsequent use. ## Footnote In other words, the ETC constructs a proton gradient between the two compartments of the mitochondria. That gradient can then be used later to produce ATP.

Question 79

A certain enzyme, "enzyme X," functions at a slightly higher pH than "enzyme Y." Between the two, which would be expected to **exist** in the mitochondrial matrix as opposed to the intermembrane space?

Answer 79

enzyme X ## Footnote The mitochondrial matrix has a slightly higher pH than the intermembrane space. This is true due to the proton gradient between the two compartments; the intermembrane space contains more protons and thus is more acidic than the matrix.

Question 80

What molecule is the **final electron acceptor** of the electron transport chain (ETC)?

Answer 80

oxygen | (O₂) ## Footnote This is why the ETC (and by extension, the Krebs cycle) cannot proceed without oxygen! Electrons are passed along the chain until they reach oxygen, which is reduced to H₂O.

Question 81

The production of ATP from ADP and inorganic phosphate (P_i) is highly thermodynamically unfavorable. What **name** is given to the concept that allows this reaction to proceed regardless?

Answer 81

reaction coupling ## Footnote This reaction, catalyzed by ATP synthase, is coupled to the highly favorable reactions of the electron transport chain and their resulting proton gradient. Remember, nonspontaneous reactions can proceed if they are coupled with sufficiently spontaneous reactions!

Question 82

How many **key complexes** (known by their Roman numerals) are present in the electron transport chain?

Answer 82

four ## Footnote Predictably, these complexes are termed complexes I, II, III, and IV.

Question 83

Which complexes of the electron transport chain (ETC) can serve as **proton pumps**?

Answer 83

* I * III * IV ## Footnote Complex II is the only exception (as well as the only ETC complex to not be a transmembrane complex, meaning that it doesn't extend all the way through the lipid bilayer).

Question 84

# True or false. The more negative the reduction potential (E_red) of a reaction, the more spontaneous its reduction will be.

Answer 84

False ## Footnote Recall from general chemistry that *positive*, not negative, electric potentials tend to correspond with more spontaneous reactions as written. Reduction potentials are no exception.

Question 85

From complex I of the electron transport chain (ETC) to complex IV, how do the reduction potentials of the involved reactions **change**?

Answer 85

The reduction potentials become **more positive**. ## Footnote This is what ensures that the ETC progresses at all: each subsequent species has a higher affinity for electrons than the previous one. This is extremely important to understand for the MCAT!

Question 86

Number the electron transport chain (ETC) complex described below. The technical name of this complex is **NADH-CoQ oxidoreductase**. It pumps four protons into the intermembrane space.

Answer 86

complex I ## Footnote The "NADH" in the name of this complex should be a major hint. Complex I is the complex at which the NADH from previous metabolic processes donates its electrons to the ETC.

Question 87

Number the electron transport chain (ETC) complex described below. This complex, termed **cytochrome c oxidase**, oxidizes cytochrome c to produce electrons that directly result in the production of H₂O.

Answer 87

complex IV ## Footnote The direct production of H₂O occurs at the end of the ETC, when electrons obtained from cytochrome c oxidation are donated to O₂ to form H₂O.

Question 88

Number the electron transport chain (ETC) complex described below. This complex **transfers electrons** one at a time to cytochrome c. Additionally, it pumps four protons into the intermembrane space.

Answer 88

complex III ## Footnote The transfer of electrons to cytochrome c (a heme-containing species that can carry a single electron at a time) is accomplished by complex III. Cytochrome c is then oxidized by complex IV, the final complex in the chain.

Question 89

Number the electron transport chain (ETC) complex described below. The name of this complex is **succinate-CoQ oxidoreductase**. It is the only complex of the ETC that does not act as a proton pump.

Answer 89

complex II ## Footnote Complex II is the "outlier" among ETC complexes, both in its acceptance of electrons from FADH₂ and in its lack of proton pump activity. When you see the technical name of this complex, the word "succinate" should remind you of its dual roles in the ETC and the Krebs cycle.

Question 90

Name the **enzyme** that combines inorganic phosphate with adenosine diphosphate as part of oxidative phosphorylation.

Answer 90

ATP synthase ## Footnote This enzyme synthesizes ATP by combining inorganic phosphate (or P_i) with adenosine diphosphate (or ADP).

Question 91

In cellular respiration, which type of **membrane transport** is utilized when protons move from the intermembrane space into the mitochondrial matrix?

Answer 91

facilitated diffusion ## Footnote This question is referring to the movement of protons through ATP synthase. Since this movement is down their concentration gradient, it is passive (diffusion); however, it is facilitated rather than simple diffusion because an ion channel is being utilized.

Question 92

Name the **two major subunits** of ATP synthase.

Answer 92

1. F₀ 2. F₁

Question 93

# Fill in the blank. The subunit of ATP synthase that is anchored firmly in the inner mitochondrial membrane is the \_\_\_\_.

Answer 93

F₀ ## Footnote Predictably, this portion of ATP synthase is hydrophobic (water-insoluble).

Question 94

# Fill in the blank. The subunit of ATP synthase that directly catalyzes the phosphorylation of ADP is the \_\_\_\_\_.

Answer 94

F₁ ## Footnote This subunit sticks out into the mitochondrial matrix rather than being embedded in the membrane. As such, it is hydrophilic.

Question 95

If a poison were administered to render the inner mitochondrial membrane permeable to ions, what would happen to **cellular respiration**?

Answer 95

The electron transport chain (ETC) would become **decoupled** from oxidative phosphorylation. ## Footnote In other words, protons would still be pumped across the membrane by the ETC (for a time, anyway), but since they could then drift right back into the matrix through the membrane, this ETC activity would no longer correspond to ATP synthesis.

Question 96

Approximately how many ATP molecules are produced for every **NADH molecule** that donates its electrons to the electron transport chain?

Answer 96

2.5 to 3 ## Footnote Sources differ on the exact value here (for a number of reasons), but for the sake of the MCAT, knowing this approximate range is more than sufficient.

Question 97

Approximately how many ATP molecules are produced for every **FADH₂ molecule** that donates its electrons to the electron transport chain?

Answer 97

1.5 to 2 ## Footnote As with NADH, it is the range here that is important to remember, not a single exact value.

Question 98

Explain why FADH₂ is **associated** with the production of fewer ATP molecules than NADH.

Answer 98

FADH₂ donates its electrons **later** in the electron transport chain (ETC) than NADH. ## Footnote Specifically, FADH₂ donates its electrons to complex II, while NADH donates its electrons to complex I. This results in some protons being pumped into the intermembrane space (by complex I) as a result of NADH alone. On average, then, NADH leads to the production of more ATP.

Question 99

Name the **metabolic process** that involves (and is actually named for) the production of new glucose.

Answer 99

gluconeogenesis ## Footnote In this term, "gluco-" refers to glucose, "-neo" means "new," and "-genesis" means "creation" or "production."

Question 100

In which **two organs** does gluconeogenesis occur?

Answer 100

It occurs in the **liver** (predominantly) and in the **kidneys**. ## Footnote This contrasts with glycolysis, which happens throughout the body tissues.

Question 101

# Define: a glucogenic amino acid

Answer 101

It is an amino acid that can be **converted into glucose** via gluconeogenesis. ## Footnote All amino acids are glucogenic except for lysine and leucine (which can be remembered on the basis of their shared first letter, "L").

Question 102

# Define: a ketogenic amino acid

Answer 102

It is an amino acid that can be **converted into acetyl-CoA** or acetoacetate (a ketone body). ## Footnote Only leucine and lysine are *exclusively* ketogenic, but a number of other amino acids are both ketogenic and glucogenic.

Question 103

Name the **five amino acids** that are both glucogenic and ketogenic.

Answer 103

1. Phenylalanine 2. Isoleucine 3. Threonine 4. Tryptophan 5. Tyrosine ## Footnote These amino acids can be remembered using the acronym PITTT (just remember that it refers to the first letter of each word, not the one-letter abbreviation of each amino acid).

Question 104

Name **at least three species** that can be used as substrates for gluconeogenesis.

Answer 104

* pyruvate * lactate * glucogenic amino acids * glycerol * odd-chain fatty acids

Question 105

# Fill in the blank. While gluconeogenesis is often thought of as glycolysis in reverse, several key reactions cannot simply be reversed because they were far too ________ in glycolysis.

Answer 105

exergonic ## Footnote Specifically, three of these irreversible reactions exist.

Question 106

Which **three reactions** of glycolysis must be bypassed using different enzymes in gluconeogenesis? ## Footnote Please answer this question using the number of the step in glycolysis.

Answer 106

1. step 1 2. step 3 3. step 10 ## Footnote These three reactions are termed "irreversible" due to their extremely exergonic, or energetically favorable, nature in the forward direction.

Question 107

Explain how gluconeogenesis bypasses **step 10** of glycolysis.

Answer 107

Pyruvate is first converted to oxaloacetate by **pyruvate carboxylase** and then converted to phosphoenolpyruvate (PEP) by **PEP carboxykinase**. ## Footnote This differs from the reverse of the glycolytic step. In this step of glycolysis, PEP is directly converted to pyruvate by **pyruvate kinase**.

Question 108

Explain how gluconeogenesis bypasses **step 3** of glycolysis.

Answer 108

Fructose 1,6-bisphosphate is converted to fructose 6-phosphate by **fructose 1,6-bisphosphatase**. ## Footnote This differs from the reverse of the glycolytic step. In this step of glycolysis, fructose 6-phosphate is transformed into fructose 1,6-bisphosphate by **phosphofructokinase**.

Question 109

Explain how gluconeogenesis bypasses **step 1** of glycolysis.

Answer 109

Glucose 6-phosphate is converted to glucose by **glucose 6-phosphatase**. ## Footnote This differs from the reverse of the glycolytic step. In this step of glycolysis, glucose is phosphorylated into glucose 6-phosphate by hexokinase (and sometimes glucokinase).

Question 110

Name the **metabolic pathway** that generates the electron carrier NADPH as well as an important nucleotide precursor.

Answer 110

pentose phosphate pathway ## Footnote While this pathway is tested far less frequently than metabolic processes like glycolysis or the Krebs cycle, you should still understand its general function. The nucleotide precursor mentioned on the front of this card is ribose 5-phosphate.

Question 111

Name the **two phases** of the pentose phosphate pathway. | (PPP)

Answer 111

1. oxidative phase 2. non-oxidative phase ## Footnote The oxidative phase produces NADPH, while the non-oxidative phase produces pentoses (five-carbon sugars) as well as the phosphorylated pentose ribose 5-phosphate.

Question 112

Name the **peptide hormone** that upregulates glycogen synthesis, inhibits gluconeogenesis, promotes the storage of lipids, and inhibits proteolysis.

Answer 112

Insulin ## Footnote Note that all of these functions relate to the *storage* of energy (rather than the generation of molecules that can be used as immediate energy sources). This should make sense, as insulin is released when abundant glucose is already available in the bloodstream.

Question 113

Name the **peptide hormone** that promotes both gluconeogenesis and glycogenolysis while also stimulating the breakdown of triglycerides.

Answer 113

Glucagon ## Footnote You may notice that these functions are exactly the opposite of those of insulin. In fact, glucagon (which is released when blood glucose levels are low) can be essentially conceptualized as insulin's "opposite" hormone.

Question 114

Is **upregulated proteolysis** (protein breakdown) more closely associated with high plasma levels of insulin or glucagon?

Answer 114

Glucagon ## Footnote Glucagon, not insulin, promotes proteolysis. Glucagon is released when blood glucose levels are low. Its stimulatory effect on proteolysis can result in the production of free amino acids that can then be fed into gluconeogenesis.

Question 115

Glycogen, the body's main source of stored glucose, is primarily stored in which **two locations**?

Answer 115

1. liver 2. skeletal muscle ## Footnote In particular, skeletal muscle stores glycogen to allow for the quick production of glucose via glycogenolysis (glycogen breakdown) when desperately needed.

Question 116

Within a linear portion of a glycogen molecule, what type of bonds connect adjacent glucose subunits?

Answer 116

* α-1 * 4-glycosidic bonds ## Footnote These 1,4 linkages connect adjacent glucose monomers in a linear, non-branching fashion. Linear chains in glycogen typically consist of around eight to 12 glucose subunits.

Question 117

A glycogen molecule is a highly branched structure that, overall, can contain tens of thousands of glucose monomers. In such a structure, what type of bonds are present at branch points?

Answer 117

* α-1 * 6-glycosidic bonds ## Footnote These differ from the typical 1,4 bonds found in linear portions.

Question 118

The creation of α-1,4-glycosidic bonds [in linear segments of glycogen/at branch points] is catalyzed by [glycogen branching enzyme/glycogen synthase]. ## Footnote Choose one term from each box above to accurately complete the sentence.

Answer 118

in linear segments of glycogen, glycogen synthase ## Footnote Remember, α-1,4-glycosidic bonds connect glucose molecules linearly, not in a branched fashion!

Question 119

The creation of α-1,6-glycosidic bonds [in linear segments of glycogen/at branch points] is catalyzed by [glycogen branching enzyme/glycogen synthase]. ## Footnote Choose one term from each box above to accurately complete the sentence.

Answer 119

at branch points, glycogen branching enzyme

Question 120

Name three distinct methods used by humans and their cells to acquire glucose.

Answer 120

1. **Eating** (acquiring glucose through the diet) 2. **Breaking down glycogen** (accessing stored glucose) 3. **Performing gluconeogenesis** (generating new glucose)