Unit 3 - Active Recall

Question 1

What is the Warburg effect?

Answer 1

The Warburg effect is a phenomenon where cancer cells exhibit increased glucose uptake and utilization even in the presence of oxygen. This metabolic shift favors glycolysis over oxidative phosphorylation for energy production, leading to elevated lactate production. It’s characterized by altered cellular metabolism, favoring rapid proliferation and tumor growth.

Question 2

What is the purpose of glycolysis…How does glycolysis work to achieve the above goal?

Answer 2

The purpose of glycolysis is to break down glucose into pyruvate while producing ATP and NADH. Glycolysis works by converting one molecule of glucose into two molecules of pyruvate through a series of enzymatic reactions. These reactions involve the investment of two ATP molecules initially and the subsequent generation of four ATP molecules, resulting in a net gain of two ATP molecules per glucose molecule. Additionally, NAD+ is reduced to NADH during glycolysis, which can then be used in oxidative phosphorylation to generate more ATP. Overall, glycolysis provides cells with energy in the form of ATP and produces intermediates for various metabolic pathways.

Question 3

What is the common feature in glycolytic reactions?
Why is such a common feature important?

Answer 3

The common feature in glycolytic reactions is the conversion of glucose into pyruvate through a series of enzymatic steps. This process occurs in the cytoplasm of cells and doesn’t require oxygen (anaerobic).

This common feature is important because it allows cells to produce energy (in the form of ATP) quickly, regardless of the availability of oxygen. Glycolysis is a fundamental metabolic pathway used by most organisms to generate energy, making it essential for cellular function and survival. Additionally, glycolysis provides intermediates for other metabolic pathways, such as the citric acid cycle and the pentose phosphate pathway, enabling cells to synthesize essential molecules and adapt to various metabolic demands.

Question 4

What are the regulatory steps in glycolysis?

Answer 4

The regulatory steps in glycolysis are primarily controlled by enzymes that catalyze key reactions. These enzymes are regulated by allosteric modulation and/or covalent modification. The key regulatory steps include:

1. Hexokinase: The phosphorylation of glucose to glucose-6-phosphate, catalyzed by hexokinase, is an early regulatory step.
2. Phosphofructokinase-1 (PFK-1): PFK-1 catalyzes the phosphorylation of fructose-6-phosphate to fructose-1,6-bisphosphate and is a major regulatory step.
3. Pyruvate kinase: The conversion of phosphoenolpyruvate (PEP) to pyruvate, catalyzed by pyruvate kinase, is another important regulatory step.
   These regulatory steps ensure that glycolysis is appropriately activated or inhibited based on the cell’s energy needs and metabolic state.

Question 5

How does pyruvate kinase regulate insulin secretion?

Answer 5

Pyruvate kinase regulates insulin secretion by controlling the production of pyruvate, a key metabolite in glucose metabolism. When glucose levels rise, pyruvate kinase activity increases, leading to higher pyruvate levels. Elevated pyruvate stimulates insulin secretion from pancreatic beta cells, promoting glucose uptake by tissues and lowering blood glucose levels.

Question 6

How can pyruvate be metabolized?
How is pyruvate metabolized in humans?

Answer 6

Pyruvate can be metabolized through various pathways. In humans, pyruvate is primarily metabolized through aerobic respiration in the mitochondria, where it is converted into acetyl-CoA by the enzyme pyruvate dehydrogenase complex (PDC). Acetyl-CoA enters the tricarboxylic acid (TCA) cycle, also known as the Krebs cycle, to generate ATP through oxidative phosphorylation. Alternatively, pyruvate can be converted into lactate under anaerobic conditions, a process known as lactate fermentation, which occurs in the cytoplasm. Additionally, pyruvate can be carboxylated to oxaloacetate by the enzyme pyruvate carboxylase for gluconeogenesis or converted into alanine through transamination reactions.

Question 7

What is the common feature in the catabolism of pyruvate?

Answer 7

The common feature in the catabolism of pyruvate is its conversion into various end products through different metabolic pathways, such as fermentation, the citric acid cycle, or gluconeogenesis.

Question 8

Why do cancers prefer to use glycolysis?

Answer 8

Cancers prefer to use glycolysis because it provides rapid production of ATP, supporting their high metabolic demands. Additionally, glycolysis generates metabolic intermediates needed for cancer cell growth and proliferation. This preference, known as the Warburg effect, allows cancer cells to thrive even in oxygen-rich environments.

Question 9

How sugars other than glucose metabolized?

Answer 9

Sugars other than glucose can be metabolized through various pathways in the body. For instance, fructose can be metabolized through the fructose 1-phosphate pathway or converted into glucose in the liver. Galactose is converted into glucose through a series of enzymatic reactions known as the Leloir pathway. Additionally, other sugars like sucrose and lactose are broken down into their constituent monosaccharides, glucose, and fructose, or glucose and galactose respectively, before being metabolized through glycolysis or other metabolic pathways. Overall, sugars other than glucose can be metabolized through different pathways to provide energy for cellular functions.

Question 10

What is the potential health impact of fructose?

Answer 10

• Increased risk of obesity due to its effect on appetite regulation and fat storage.
• Elevated risk of metabolic syndrome, characterized by high blood pressure, insulin resistance, and abdominal obesity.
• Higher likelihood of developing non-alcoholic fatty liver disease (NAFLD) due to fructose metabolism in the liver.
• Association with type 2 diabetes, as excessive fructose consumption can lead to insulin resistance.
• Potential contribution to cardiovascular diseases, such as heart disease and stroke, through its impact on blood lipid levels and inflammation.

Question 11

What is the purpose of GNG? Where does GNG take place?

Answer 11

The purpose of gluconeogenesis is to produce glucose from non-carbohydrate sources, such as amino acids and glycerol, especially when glucose levels are low in the body. Gluconeogenesis primarily occurs in the liver and to a lesser extent in the kidneys.

Question 12

How does GNG work if we start with pyruvate?

Answer 12

Gluconeogenesis is a metabolic pathway that synthesizes glucose from non-carbohydrate precursors. Starting with pyruvate, an intermediate product of glycolysis, gluconeogenesis involves a series of enzymatic reactions. Pyruvate is first converted to oxaloacetate, a process catalyzed by the enzyme pyruvate carboxylase. Oxaloacetate is then converted to phosphoenolpyruvate (PEP) by the enzyme phosphoenolpyruvate carboxykinase (PEPCK). PEPCK catalyzes the conversion of oxaloacetate to PEP through the removal of a carbon dioxide molecule and the addition of a phosphate group. Finally, PEP is converted to glucose through several additional enzymatic steps within the gluconeogenesis pathway. Overall, gluconeogenesis allows the body to produce glucose from non-carbohydrate sources like pyruvate, ensuring a constant supply of this essential energy molecule.

Question 13

How does GNG convert lactate, alanine, or glycerol to glucose?

Answer 13

Lactate is converted into pyruvate through the action of lactate dehydrogenase. Pyruvate then enters the gluconeogenic pathway where it undergoes a series of conversions, including carboxylation to form oxaloacetate, which eventually leads to the production of glucose.

Alanine is converted into pyruvate and then follows a similar pathway to lactate, entering gluconeogenesis to ultimately yield glucose.

Glycerol, derived from the breakdown of fats, is converted into dihydroxyacetone phosphate (DHAP), an intermediate in glycolysis. DHAP is then converted into glyceraldehyde 3-phosphate and enters gluconeogenesis to contribute to glucose synthesis.

Overall, gluconeogenesis involves multiple steps and enzymes to convert these non-carbohydrate precursors into glucose, providing an essential pathway for maintaining blood glucose levels during fasting or periods of low carbohydrate intake.

Question 14

Why is lactate shuttling useful?

Answer 14

Lactate shuttling is beneficial because it allows for the efficient transfer of lactate between tissues, facilitating energy production and metabolism.

Question 15

How is GNG regulated?

Answer 15

regulated by several key factors including hormonal signals such as glucagon and cortisol, substrate availability, and allosteric regulation of enzymes involved in the pathway.

Question 16

Why cannot we just reverse glycolysis to achieve GNG?

Answer 16

Reversing glycolysis to achieve gluconeogenesis (GNG) isn’t straightforward because several steps in glycolysis are energetically unfavorable, requiring different enzymes or bypass pathways in GNG.

Question 17

What are the similarities and differences between glycolysis and GNG?

Answer 17

Glycolysis and gluconeogenesis (GNG) both involve the metabolism of sugars but differ in their direction and purpose. Glycolysis breaks down glucose into pyruvate to produce energy, while GNG synthesizes glucose from non-carbohydrate sources like amino acids or fats.

Question 18

review: https://quizlet.com/786729695/biochem-midterm-3-lec-4-flash-cards/

Question 19

Why is succinate dehydrogenase the only enzyme in TCA that is imbedded in IMM?

Answer 19

Succinate dehydrogenase is the only enzyme in the tricarboxylic acid (TCA) cycle that is embedded in the inner mitochondrial membrane (IMM) because it is also part of the electron transport chain (ETC). This enzyme is unique because it catalyzes both the conversion of succinate to fumarate in the TCA cycle and the transfer of electrons to the ETC via FADH2, ultimately contributing to the generation of ATP through oxidative phosphorylation. Its location within the inner mitochondrial membrane allows for direct transfer of electrons to the ETC, facilitating efficient energy production within the mitochondria.

Question 20

Even though TCA cycle does not use O2 directly, why would we still say TCA cycle depend on O2?

Answer 20

While the TCA (tricarboxylic acid) cycle itself doesn’t directly consume oxygen, it’s intricately linked to oxidative phosphorylation, a process that relies on oxygen as the final electron acceptor. NADH and FADH2, generated in the TCA cycle, donate electrons to the electron transport chain (ETC), which couples electron transfer to proton pumping across the inner mitochondrial membrane. Oxygen is essential for the ETC to function efficiently by serving as the terminal electron acceptor, allowing the regeneration of NAD+ and FAD, crucial for sustaining the TCA cycle. Therefore, despite not directly utilizing oxygen, the TCA cycle depends on it indirectly through its interconnection with oxidative phosphorylation for efficient ATP production.

Question 21

Why is pyruvate dehydrogenase complex important in aerobic respiration?

Answer 21

The pyruvate dehydrogenase complex is crucial in aerobic respiration because it facilitates the conversion of pyruvate, a product of glycolysis, into acetyl-CoA. This conversion is vital as it links glycolysis, which occurs in the cytoplasm, with the TCA cycle, which takes place in the mitochondria. Acetyl-CoA then enters the TCA cycle where it undergoes further oxidation, generating reducing equivalents such as NADH and FADH2, which are essential for ATP production through oxidative phosphorylation. Thus, the pyruvate dehydrogenase complex plays a central role in the efficient utilization of glucose for energy production in aerobic conditions.

Question 22

What are the important biological functions of TCA cycle?

Answer 22

The Tricarboxylic Acid (TCA) cycle, also known as the Krebs cycle, plays crucial roles in cellular respiration and metabolism. Its primary functions include:

1. Energy Production: The TCA cycle serves as a central hub for the oxidation of acetyl-CoA derived from carbohydrates, fats, and proteins, generating reducing equivalents (NADH and FADH2) that fuel the electron transport chain, ultimately producing ATP through oxidative phosphorylation.
2. Biosynthesis: Intermediates of the TCA cycle are essential precursors for the synthesis of amino acids, nucleotides, and other important cellular components. For example, α-ketoglutarate is a precursor for amino acid synthesis, and oxaloacetate is a precursor for gluconeogenesis.
3. Redox Balance: The cycle also helps maintain the balance of reducing equivalents (NADH and FADH2) and oxidized cofactors (NAD+ and FAD) within the cell, which is critical for various metabolic processes and redox signaling.

Overall, the TCA cycle is integral to cellular metabolism, providing both energy and building blocks necessary for cell growth, maintenance, and function.

Question 23

What are the two stages of TCA cycle and how they are separated?

Answer 23

Stage 1: Rxns 1-4 (irreversible)
acetyl coa + oxalocatate —> citrate —-> CO2 as byproduct and succinyl coa as product

Stage 2: Rxns 5-8 (reversible)
succinyl coa —–recycles——> oxalocatate

Question 24

How does TCA cycle work in stepwise cyclic manner?

Answer 24

The tricarboxylic acid (TCA) cycle, also known as the citric acid cycle, operates in a stepwise cyclic manner to oxidize acetyl-CoA derived from carbohydrates, fats, and proteins. It begins with the condensation of acetyl-CoA and oxaloacetate to form citrate, which undergoes a series of enzymatic reactions, including isomerization, decarboxylation, and redox reactions, leading to the regeneration of oxaloacetate. These reactions result in the production of reducing equivalents in the form of NADH and FADH2, as well as GTP (which can be converted to ATP). This cyclic process ultimately facilitates the complete oxidation of acetyl-CoA and the generation of high-energy electron carriers for oxidative phosphorylation in the electron transport chain.

Question 25

What are the irreversible steps of the TCA cycles? How is TCA cycle regulated?

Answer 25

The irreversible steps in the TCA (tricarboxylic acid) cycle are typically enzyme-catalyzed reactions that have a large negative change in free energy, making them thermodynamically unfavorable to reverse. These steps include the conversion of citrate to isocitrate, isocitrate to α-ketoglutarate, and α-ketoglutarate to succinyl-CoA. The TCA cycle is regulated primarily through substrate availability and allosteric regulation of key enzymes.

High levels of ATP and NADH signal a reduced need for energy production, slowing down the cycle through feedback inhibition of enzymes like isocitrate dehydrogenase and α-ketoglutarate dehydrogenase. Conversely, ADP and NAD+ act as activators, stimulating TCA cycle activity when energy demand is high. Hormonal regulation and post-translational modifications also play roles in modulating enzyme activity within the cycle.

Question 26

What is the net reaction of TCA cycle?

Answer 26

3 NADH, 2 CO2, 1 ATP AND 1 FADH2 (AND OR ACETYL COA)

Question 27

How does fluoroacetate impeded metabolism?

Answer 27

Fluoroacetate is a potent metabolic poison primarily because it inhibits the enzyme aconitase in the citric acid cycle (also known as the tricarboxylic acid cycle or TCA cycle). Aconitase catalyzes the conversion of citrate to isocitrate, a crucial step in the cycle. By disrupting this process, fluoroacetate effectively halts the TCA cycle, which is vital for generating energy through the oxidation of acetyl-CoA and producing reducing equivalents like NADH and FADH2. Consequently, cellular metabolism is severely impaired, leading to a cascade of metabolic disruptions and eventually cell death.

Question 28

Why do we need electron transport chain?

Answer 28

The electron transport chain is needed to generate ATP, the main energy currency of cells, by transferring electrons through a series of protein complexes embedded in the inner mitochondrial membrane, ultimately driving the synthesis of ATP from ADP and inorganic phosphate.

Question 29

How do cells import cytosolic NADH into mitochondria?

Answer 29

Cells import cytosolic NADH into mitochondria through a shuttle system, such as the malate-aspartate shuttle or the glycerol-3-phosphate shuttle, which transfer reducing equivalents from NADH to the mitochondrial matrix, where they can participate in oxidative phosphorylation.

Question 30

How does electron transport chain work?

Answer 30

1. Electron Donation: The process begins with the donation of high-energy electrons from molecules such as NADH (Nicotinamide adenine dinucleotide) and FADH2 (Flavin adenine dinucleotide), which are produced in previous stages of cellular respiration (glycolysis, pyruvate oxidation, and the Krebs cycle).
2. Electron Movement: These high-energy electrons are then passed along a series of protein complexes embedded in the inner mitochondrial membrane (or the plasma membrane in prokaryotic cells). As electrons move from one complex to the next, they gradually lose energy.
3. Proton Pumping: As electrons pass through the protein complexes, energy is released and used to pump protons (H+ ions) from the mitochondrial matrix (or the cytoplasm in prokaryotic cells) into the intermembrane space, creating a proton gradient.
4. Chemiosmosis: The proton gradient created across the inner mitochondrial membrane (or the plasma membrane in prokaryotic cells) represents potential energy. Protons flow back into the mitochondrial matrix (or the cytoplasm in prokaryotic cells) through ATP synthase, a complex enzyme embedded in the membrane. This movement of protons drives the rotation of ATP synthase, allowing it to catalyze the synthesis of ATP from adenosine diphosphate (ADP) and inorganic phosphate (Pi). This process is known as chemiosmosis.
5. Oxygen as the Terminal Electron Acceptor: At the end of the electron transport chain, oxygen serves as the terminal electron acceptor. It combines with electrons and protons to form water (H2O). This step is crucial for maintaining the flow of electrons through the chain; without oxygen, the electron transport chain would cease to function.

Question 31

Why is the electron transport chain organized the way it is?

Answer 31

The electron transport chain (ETC) is organized in a specific manner to maximize energy efficiency and facilitate the production of ATP, the cell’s primary energy currency. Here’s why it’s structured the way it is:

1. Sequential Arrangement: The electron transport chain consists of a series of protein complexes embedded in the inner mitochondrial membrane (in eukaryotes) or the plasma membrane (in prokaryotes). Electrons flow sequentially from one complex to another in a specific order. This sequential arrangement ensures that each step releases energy gradually, which can be efficiently harvested.
2. Redox Potential Gradient: Each complex in the electron transport chain has a different redox potential. This means that as electrons pass through the chain, they move from higher to lower energy states. This gradient of redox potentials drives the movement of electrons, allowing for the release of energy that is harnessed to pump protons across the membrane.
3. Proton Pumping: As electrons move through the electron transport chain, energy is released and used to pump protons (H⁺ ions) across the inner mitochondrial membrane (or plasma membrane in prokaryotes), creating a proton gradient or proton motive force. This proton gradient is essential for ATP synthesis.
4. ATP Synthase: At the end of the electron transport chain, the enzyme ATP synthase utilizes the energy stored in the proton gradient to produce ATP from ADP and inorganic phosphate (Pi). Protons flow back across the membrane through ATP synthase, driving the rotation of the enzyme’s rotor and facilitating ATP synthesis.
5. Oxygen as the Final Electron Acceptor: In aerobic respiration, oxygen serves as the final electron acceptor in the electron transport chain. This is crucial because oxygen has a high affinity for electrons and serves as an efficient electron sink. Its reduction to water ensures that the electron transport chain can continue operating, preventing the accumulation of electrons and maintaining the flow of electrons down the chain.

Question 32

How to use reduction potential to reconstruct biological relevant reactions? How to use reduction potential to calculate Gibbs free energy?

Answer 32

To reconstruct biologically relevant reactions using reduction potential:

1. Identify the half-reactions involved in the reaction.
2. Determine the reduction potential (E°) for each half-reaction.
3. Assign electrons to balance the half-reactions.
4. Combine the balanced half-reactions to form the overall reaction.
5. To calculate Gibbs free energy (ΔG) using reduction potential:

Determine the reduction potential (E°) for the reaction.
1. Use the equation: ΔG = -nFΔE°, where n is the number of moles of electrons transferred and F is Faraday’s constant (96,485 C/mol).
2. Calculate ΔG using the given reduction potential and the number of electrons transferred.

Question 33

How many ATP molecules are produced from oxidation of 1 glucose?

Answer 33

The oxidation of 1 glucose molecule produces approximately 36 to 38 molecules of ATP through cellular respiration.

See slides from lecture 21

Question 34

What are the effects of uncoupling proteins? What about uncouplers?

Answer 34

The effects of uncoupling proteins involve the dissipation of the proton gradient across the inner mitochondrial membrane, which decreases the efficiency of ATP production. Uncouplers, on the other hand, directly disrupt the coupling between electron transport and ATP synthesis, leading to increased metabolic rate and heat production.

Question 35

What are the similarities and differences between uncouple proteins and uncouplers?

Answer 35

Similarities:
- Uncoupling proteins and uncouplers both affect the process of oxidative phosphorylation in mitochondria.
- Both can lead to the dissipation of the proton gradient across the inner mitochondrial membrane.
- They both result in the generation of heat in brown adipose tissue or cells.

Differences:
- Uncoupling proteins are endogenous proteins found in the inner mitochondrial membrane, whereas uncouplers are exogenous compounds that can artificially uncouple oxidative phosphorylation.
- Uncoupling proteins are regulated by physiological factors, while uncouplers are typically synthetic chemicals.
- Uncoupling proteins are involved in physiological processes such as thermogenesis and metabolic regulation, while uncouplers are often used for experimental or therapeutic purposes.

Question 36

How does uncoupler affect health and disease? How does uncoupling proteins contribute to diabetes?

Answer 36

Uncouplers are compounds that disrupt the coupling of electron transport and ATP synthesis in mitochondria, leading to increased energy expenditure and heat production. While this can potentially aid in weight loss, prolonged uncoupling may contribute to metabolic disorders like diabetes by disrupting energy balance and glucose homeostasis.

Uncoupling proteins, specifically UCP2 and UCP3, have been implicated in diabetes by altering insulin secretion, glucose uptake, and fatty acid metabolism in cells, potentially leading to insulin resistance and impaired glucose tolerance.

Question 37

How do different drugs inhibit electron transport chain?

Answer 37

1. Rotenone and Amytal: These inhibitors act at Complex I (NADH dehydrogenase) of the ETC. Rotenone binds to the Fe-S clusters of Complex I, while Amytal binds to the ubiquinone binding site. By blocking Complex I, they prevent the transfer of electrons from NADH to ubiquinone, thereby disrupting electron flow.
2. Antimycin A: This compound inhibits Complex III (cytochrome bc1 complex) by binding to the Qi site, preventing the transfer of electrons from cytochrome b to cytochrome c.
3. Cyanide and Carbon Monoxide: Both cyanide and carbon monoxide bind to Complex IV (cytochrome c oxidase) and inhibit its activity. Cyanide binds to the ferric ion (Fe3+) in the heme group of cytochrome oxidase, whereas carbon monoxide binds to the same site but with much higher affinity, thereby blocking the reduction of oxygen to water.
4. Oligomycin: This inhibitor targets Complex V (ATP synthase). It binds to the F0 subunit of ATP synthase, blocking the flow of protons through the F0 channel and thus inhibiting ATP synthesis.
5. 2,4-Dinitrophenol (DNP): DNP is a proton ionophore that disrupts the proton gradient across the inner mitochondrial membrane. It increases the permeability of the membrane to protons, causing a short-circuiting of the proton gradient and uncoupling oxidative phosphorylation from ATP synthesis.

Question 38

What are the consequences of drug induced inhibition of electron transport chain?

Answer 38

Drug-induced inhibition of the electron transport chain can lead to a decrease in ATP production, disruption of cellular respiration, oxidative stress due to accumulation of reactive oxygen species, and potential damage to tissues and organs, contributing to various health issues including metabolic disorders, neurodegenerative diseases, and cardiovascular complications.

Question 39

How does the digestive system breakdown and absorb fats from food?

Answer 39

The digestive system breaks down and absorbs fats through a process involving several steps. First, in the stomach, gastric lipase begins to break down some dietary fats into smaller molecules. Once in the small intestine, bile salts emulsify large fat globules into smaller droplets, increasing their surface area for enzymatic action. Pancreatic lipase then hydrolyzes triglycerides into monoglycerides and fatty acids, which are further broken down by other enzymes into absorbable forms. These breakdown products are then absorbed across the intestinal epithelium, forming micelles, which are transported into enterocytes. Inside the enterocytes, these fats are re-esterified into triglycerides and packaged into chylomicrons, which are released into the lymphatic system and eventually enter the bloodstream for distribution to tissues throughout the body.

Question 40

How is triacylglycerol metabolized?

Answer 40

Triacylglycerol (TAG) is metabolized through lipolysis, where it is broken down into glycerol and fatty acids by lipase enzymes. These components are then further processed: glycerol can enter glycolysis as dihydroxyacetone phosphate, while fatty acids undergo beta-oxidation to produce acetyl-CoA, which enters the citric acid cycle to generate ATP through oxidative phosphorylation. Excess acetyl-CoA derived from fatty acid oxidation can also be converted into ketone bodies in the liver. Overall, TAG metabolism provides a significant source of energy for the body during periods of fasting or prolonged energy demands.

Question 41

How is saturated even numbered fatty acid oxidized…How is saturated odd numbered fatty acid oxidized?

Answer 41

Saturated even-numbered fatty acids undergo β-oxidation, a cyclic process in which the fatty acid chain is sequentially shortened by two carbons with each cycle. Each round of β-oxidation involves four enzymatic steps: (1) dehydrogenation, (2) hydration, (3) dehydrogenation, and (4) thiolysis, resulting in the release of one acetyl-CoA molecule per cycle.

Saturated odd-numbered fatty acids are oxidized similarly to even-numbered ones until the last round of β-oxidation, where a three-carbon fragment (propionyl-CoA) remains. Propionyl-CoA is converted to succinyl-CoA via a series of enzymatic reactions in the propionate pathway, which can then enter the TCA cycle after conversion to oxaloacetate. This process involves biotin-dependent carboxylation and requires vitamin B12 as a cofactor.

Question 42

How many ATP molecules are produced from oxidation of fatty acids?

Answer 42

The exact ATP yield from the oxidation of fatty acids varies depending on the length and saturation of the fatty acid chain. However, as a general rule, the oxidation of fatty acids through beta-oxidation and the subsequent TCA cycle and oxidative phosphorylation can yield a significant amount of ATP. On average, the complete oxidation of one molecule of a typical fatty acid can produce around 129 ATP molecules.

Question 43

How are ketone bodies made? How are ketone bodies used for energy?

Answer 43

Ketone bodies are produced in the liver through a process called ketogenesis. During times of low glucose availability, such as prolonged fasting or starvation, fatty acids are mobilized from adipose tissue and transported to the liver. Within the liver, fatty acids undergo β-oxidation to generate acetyl-CoA molecules. When the supply of oxaloacetate is limited due to its conversion to glucose through gluconeogenesis, excess acetyl-CoA is diverted towards ketogenesis. Acetyl-CoA molecules are then condensed to form ketone bodies: acetoacetate and β-hydroxybutyrate.

Ketone bodies can be used for energy primarily by extrahepatic tissues such as the brain, heart, and skeletal muscles. They are transported through the bloodstream to these tissues where they are converted back into acetyl-CoA. This acetyl-CoA enters the TCA cycle to generate ATP through oxidative phosphorylation, providing an alternative fuel source when glucose availability is limited.

Question 44

Why can liver only make but not use ketone bodies for energy?

Answer 44

The liver cannot use ketone bodies for energy due to the absence of CoA transferase, an enzyme necessary for converting ketone bodies into acetyl-CoA, which is the primary substrate for the TCA cycle. Therefore, while the liver can produce ketone bodies via ketogenesis, it cannot directly utilize them for energy. Instead, ketone bodies are exported from the liver to other tissues for energy production.

Question 45

Why cannot liver use acetyl-CoA for energy under extensive starvation, while other issues can?

Answer 45

During extensive starvation, when glucose levels are low, the liver primarily generates ketone bodies from acetyl-CoA to provide alternative fuel for the body, especially the brain. However, the liver itself cannot utilize these ketone bodies for energy due to the lack of the necessary enzyme, succinyl-CoA:3-ketoacid CoA transferase. This enzyme is essential for converting ketone bodies back into acetyl-CoA for entry into the citric acid cycle. Therefore, while other tissues can utilize ketone bodies for energy, the liver predominantly synthesizes ketone bodies but cannot efficiently use them, prioritizing their supply to other organs.

Question 46

How does ketogenesis fuel the body during starvation by preserving muscles?

Answer 46

During starvation, when glucose levels are depleted, the body turns to alternative fuel sources such as ketone bodies produced through ketogenesis. Ketone bodies are derived from fatty acids and can be used by tissues, including the brain, as an energy source, thereby sparing glucose for cells that rely on it. By utilizing ketone bodies, the body reduces the breakdown of muscle protein for gluconeogenesis, thus preserving muscle mass during prolonged fasting or starvation. This mechanism helps to maintain vital functions and energy production while minimizing muscle wasting.

Question 47

How does ketogenesis contribute to ketoacidosis in diabetics, but not healthy people?

Answer 47

In diabetic individuals, particularly those with uncontrolled diabetes, insufficient insulin levels lead to unchecked lipolysis and excessive ketogenesis. This results in an overproduction of ketone bodies, leading to a condition known as ketoacidosis. Healthy individuals, on the other hand, have regulated insulin levels that prevent excessive lipolysis and ketogenesis, thereby avoiding the development of ketoacidosis.

Question 48

What is the overarching scheme for lipid synthesis?

Answer 48

The overarching scheme for lipid synthesis involves the conversion of acetyl-CoA, derived from various metabolic pathways such as glycolysis and beta-oxidation of fatty acids, into fatty acids. These fatty acids are then further processed through fatty acid synthesis pathways to generate various types of lipids, including triglycerides, phospholipids, and cholesterol esters. The process typically occurs in the cytoplasm for fatty acid synthesis and involves a series of enzymatic reactions mediated by enzymes such as Acetyl-CoA carboxylase and fatty acid synthase. Lipid synthesis is tightly regulated and essential for cellular structure, energy storage, and signaling.

Question 49

How is fatty acid synthesized in cells: even-numbered, odd-numbered, longer than C16, unsaturated fatty acids?

Answer 49

1. Even-numbered fatty acids are synthesized through repetitive addition of 2-carbon units (acetyl-CoA) via fatty acid synthase (FAS) in the cytoplasm.
2. Odd-numbered fatty acids are synthesized similarly to even-numbered fatty acids until the final step. In the last step, propionyl-CoA is added, leading to the synthesis of odd-numbered fatty acids.
3. Fatty acids longer than C16 are synthesized in the endoplasmic reticulum (ER) through the fatty acid elongation pathway, utilizing malonyl-CoA and acetyl-CoA as substrates.
4. Unsaturated fatty acids are synthesized by desaturases, enzymes that introduce double bonds into the fatty acid chains. These desaturases introduce double bonds between specific carbon atoms, usually between C9 and C10 or C12 and C13, depending on the specific fatty acid.

Question 50

What are the energy and substrate investment for fatty acid synthesis?

Answer 50

Energy: Fatty acid synthesis requires ATP as an energy source.

Substrate: Fatty acid synthesis requires acetyl-CoA and malonyl-CoA as substrates.

Question 51

What are the differences in fatty acid synthesis and fatty acid oxidation?

Answer 51

Fatty Acid Synthesis
- Location: Primarily occurs in the cytoplasm of cells, specifically in the liver and adipose tissue.
- Purpose: To produce fatty acids, which are essential for building cell membranes, storing energy, and serving as signaling molecules.
- Starting Molecule: Acetyl-CoA, which is formed from citrate in the cytoplasm and serves as the building block for fatty acid synthesis.
- Enzyme: Involves the enzyme fatty acid synthase complex, which catalyzes the stepwise addition of two-carbon units to form long-chain fatty acids.
- Energy Requirement: Requires ATP and NADPH as reducing equivalents.
- End Product: Produces saturated or monounsaturated fatty acids.

Fatty Acid Oxidation (Beta-Oxidation):
- Location: Primarily occurs in the mitochondria of cells, particularly in tissues with high energy demands such as muscle and liver.
- Purpose: To break down fatty acids to generate ATP, especially during periods of fasting or prolonged exercise.
- Starting Molecule: Fatty acids derived from triglycerides or other lipid stores.
- Enzyme: Involves a series of enzymes collectively known as the beta-oxidation pathway, which sequentially removes two-carbon units from the fatty acid chain.
- Energy Release: Produces acetyl-CoA, FADH2, and NADH, which enter the citric acid cycle and electron transport chain to generate ATP.
- End Product: Produces acetyl-CoA, which enters the citric acid cycle for further energy production.

Question 52

Why do some cancers upregulate fatty acid synthesis?

Answer 52

Some cancers upregulate fatty acid synthesis to support their rapid proliferation and growth. Fatty acids serve as essential components for the construction of cellular membranes, signaling molecules, and energy storage. By increasing fatty acid synthesis, cancer cells ensure a steady supply of lipids for membrane formation, which is crucial for their increased proliferation rate. Additionally, fatty acids can act as signaling molecules to promote cancer cell survival and progression. Therefore, upregulating fatty acid synthesis provides cancer cells with the necessary building blocks and signaling molecules to sustain their rapid growth and proliferation.

Question 53

How do cells synthesize triacylglycerol and cholesterol?

Answer 53

Cells synthesize triacylglycerol (TAG) through a process called lipogenesis, which primarily occurs in the cytoplasm. It involves the esterification of glycerol with three fatty acid molecules. The fatty acids are activated and linked to Coenzyme A (CoA) before being attached to glycerol-3-phosphate. Then, a series of enzymatic reactions convert glycerol-3-phosphate to TAG.

Cholesterol synthesis, on the other hand, occurs mainly in the endoplasmic reticulum and cytoplasm. It begins with the condensation of acetyl-CoA to form acetoacetyl-CoA and then 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA). HMG-CoA is converted to mevalonate by HMG-CoA reductase, a rate-limiting enzyme in cholesterol synthesis. Mevalonate undergoes a series of enzymatic reactions, ultimately leading to the production of cholesterol.

Question 54

How does alcohol damage liver metabolism?

Answer 54

• Increased fat deposition: Alcohol metabolism generates excess NADH, leading to an increased synthesis of fatty acids and triglycerides, causing fatty liver (steatosis).
  Inflammation and oxidative stress: Alcohol metabolism produces reactive oxygen species (ROS) and activates inflammatory pathways, leading to oxidative stress and inflammation, which can damage liver cells.
• Disruption of protein synthesis: Alcohol impairs the synthesis of proteins essential for liver function, including enzymes involved in metabolism and structural proteins.
• Alteration of mitochondrial function: Alcohol interferes with mitochondrial function, leading to impaired energy production and increased oxidative stress.
• Activation of fibrosis and cirrhosis: Prolonged alcohol consumption can lead to liver fibrosis and cirrhosis, characterized by the accumulation of scar tissue, which disrupts liver architecture and function.
• Interference with nutrient metabolism: Alcohol consumption can interfere with the metabolism of essential nutrients such as vitamins and minerals, further compromising liver function and overall health.

Question 55

How do cells transport cholesterol and triacylglycerol?

Answer 55

Cells transport cholesterol and triacylglycerol through lipoproteins. Lipoproteins are complex particles consisting of a core of cholesterol esters and triacylglycerols surrounded by a shell of phospholipids, free cholesterol, and apolipoproteins. These lipoproteins are transported through the bloodstream to various tissues, where they are taken up by cells via receptor-mediated endocytosis. Once inside the cell, cholesterol and triacylglycerol can be utilized for various cellular processes such as membrane synthesis, energy production, and hormone synthesis.