1. Which of the following TCA cycle intermediates plays a crucial role in de novo fatty acid synthesis by providing substrate and positively regulating the rate-limiting enzyme involved in fatty acid synthesis?
A. Citrate
B. Isocitrate
C. Malate
D. Oxaloacetate
E. Succinate
Correct Answer: A. Citrate. Citrate plays a crucial role in de novo fatty acid synthesis as it is transported from the mitochondria to the cytoplasm, where it is cleaved by ATP-citrate lyase to generate acetyl-CoA, the main building block for fatty acid synthesis. Citrate also acts as an allosteric activator of acetyl-CoA carboxylase (ACC), the rate-limiting enzyme in fatty acid synthesis, enhancing the enzyme’s activity and promoting fatty acid production.
Incorrect Options:
B. Isocitrate: Although isocitrate is an intermediate in the TCA cycle, it does not play a direct role in fatty acid synthesis. Its main function is within the TCA cycle for energy production, and it is not involved in activating or providing substrates for fatty acid synthesis.
C. Malate: Malate can be converted into pyruvate via the malic enzyme, generating NADPH, which is used in fatty acid synthesis. However, malate itself does not provide the direct carbon substrate or activate the rate-limiting enzyme for fatty acid synthesis as citrate does.
D. Oxaloacetate: Oxaloacetate is an important TCA cycle intermediate that helps regenerate citrate by combining with acetyl-CoA, but it does not directly contribute to fatty acid synthesis. Oxaloacetate also remains primarily in the TCA cycle without directly activating ACC or providing carbon for fatty acid synthesis.
E. Succinate: Succinate is involved in the TCA cycle as an intermediate that contributes to energy production but has no direct role in fatty acid synthesis or regulation of ACC.
2. The conversion of Acetyl-CoA to Malonyl-CoA is a critical step in fatty acid synthesis, with certain molecules serving as activators. Which of the following is the most potent activator in this biochemical conversion?
A. Acetyl-CoA
B. Citrate
C. Long-chain fatty acids
D. Malate
E. Palmitic acid
Correct Answer: B. Citrate. Citrate is the most potent activator of acetyl-CoA carboxylase (ACC), the enzyme that catalyzes the conversion of acetyl-CoA to malonyl-CoA. Citrate promotes ACC activity by facilitating its polymerization, which enhances the enzyme’s ability to catalyze this crucial step in fatty acid synthesis. Citrate thus plays a dual role as both a substrate source and an allosteric activator.
Incorrect Options:
A. Acetyl-CoA: While acetyl-CoA is the substrate in this reaction, it does not serve as an activator for ACC. Its role is to provide the carbon needed for malonyl-CoA formation, but it does not enhance ACC activity.
C. Long-chain fatty acids: Long-chain fatty acids, including derivatives like palmitoyl-CoA, actually inhibit ACC as part of feedback regulation to prevent excessive fatty acid synthesis. They signal that enough fatty acids are present, thus downregulating ACC activity.
D. Malate: Malate is involved in the TCA cycle and can generate NADPH when converted by the malic enzyme, indirectly supporting fatty acid synthesis. However, it does not directly activate ACC or impact this conversion step.
E. Palmitic acid: Palmitic acid, a long-chain fatty acid, inhibits ACC activity as a feedback mechanism. It signals a sufficient level of fatty acid availability, thereby downregulating further synthesis.
3. The activity of acetyl-CoA carboxylase (ACC), a crucial enzyme in fatty acid synthesis, can be influenced by various factors. Which of the following conditions favors the inactivation of acetyl-CoA carboxylase?
A. Cytosolic citrate levels are high
B. It is dephosphorylated
C. It is in a polymeric form
D. Palmitoyl-CoA levels are low
E. The tricarboxylate transporter is inhibited
Correct Answer: E. The tricarboxylate transporter is inhibited. When the tricarboxylate transporter is inhibited, citrate cannot be exported from the mitochondria to the cytoplasm, reducing the cytosolic citrate levels needed for activating ACC. This inhibition favors the inactivation of ACC.
Incorrect Options:
A. Cytosolic citrate levels are high: High levels of cytosolic citrate activate ACC by promoting its polymerization, which favors the active form of the enzyme.
B. It is dephosphorylated: Dephosphorylation activates ACC, making it more likely to facilitate fatty acid synthesis.
C. It is in a polymeric form: ACC is active in its polymeric form. Inactivation would require ACC to remain in its dimeric form, which is favored in energy-depleted conditions to prevent fatty acid synthesis.
D. Palmitoyl-CoA levels are low: High levels of palmitoyl-CoA act as a feedback inhibitor of ACC. However, low levels of palmitoyl-CoA would reduce this inhibition, potentially allowing ACC activity to proceed.
4. Which of the following metabolic conversions provides reducing power for fatty acid synthesis?
A. Acetyl-CoA → Malonyl-CoA
B. Citrate → Acetyl-CoA + Oxaloacetate
C. Glucose 6-phosphate → 6-Phosphogluconate
D. Glyceraldehyde 3-phosphate → 1,3-Bisphosphoglycerate
E. Pyruvate → Acetyl-CoA
Correct Answer: C. Glucose 6-phosphate → 6-phosphogluconate. This conversion occurs in the pentose phosphate pathway, which generates NADPH as a byproduct. NADPH provides the reducing power required for fatty acid synthesis, supplying the electrons needed for the reduction reactions that occur in the fatty acid synthesis pathway.
Incorrect Options:
A. Acetyl-CoA → Malonyl-CoA: This step is catalyzed by acetyl-CoA carboxylase (ACC) and is crucial for fatty acid synthesis. However, it does not produce NADPH or any other reducing power; instead, it uses ATP.
B. Citrate → Acetyl-CoA + Oxaloacetate: This reaction generates acetyl-CoA in the cytoplasm for fatty acid synthesis but does not directly produce NADPH. It is an essential step in transporting acetyl-CoA from the mitochondria to the cytoplasm, yet it does not contribute to reducing power.
D. Glyceraldehyde 3-phosphate → 1,3-Bisphosphoglycerate: This reaction occurs in glycolysis and involves the reduction of NAD+ to NADH, not NADPH. NADH is primarily used in the electron transport chain for ATP production, not in fatty acid synthesis.
E. Pyruvate → Acetyl-CoA: This conversion is catalyzed by the pyruvate dehydrogenase complex and produces NADH, not NADPH. NADH is involved in energy production, not fatty acid synthesis.
5. Nicotinamide adenine dinucleotide phosphate in its reduced form (NADPH) plays a pivotal role in various biosynthetic pathways and is synthesized through specific enzymatic reactions. Which enzyme is chiefly responsible for the synthesis of NADPH?
A. Glyceraldehyde 3-phosphate dehydrogenase
B. Malate dehydrogenase
C. Pyruvate dehydrogenase
D. Glucose 6-phosphate dehydrogenase
E. Succinate dehydrogenase
Correct Answer: D. Glucose 6-phosphate dehydrogenase. Glucose 6-phosphate dehydrogenase (G6PD) is the key enzyme responsible for the synthesis of NADPH. It catalyzes the first step in the pentose phosphate pathway (PPP), where glucose 6-phosphate is converted into 6-phosphogluconolactone, generating NADPH as a byproduct. NADPH produced in the PPP is essential for reductive biosynthesis, including fatty acid and nucleotide synthesis, and for maintaining cellular redox balance.
Incorrect Options:
A. Glyceraldehyde 3-phosphate dehydrogenase: This enzyme is involved in glycolysis, where it converts glyceraldehyde 3-phosphate to 1,3-bisphosphoglycerate, producing NADH, not NADPH.
B. Malate dehydrogenase: Malate dehydrogenase catalyzes the interconversion of malate and oxaloacetate in the TCA cycle, producing NADH, not NADPH.
C. Pyruvate dehydrogenase: Pyruvate dehydrogenase catalyzes the conversion of pyruvate to acetyl-CoA and produces NADH as a byproduct. It does not produce NADPH.
E. Succinate dehydrogenase: Succinate dehydrogenase is a TCA cycle enzyme that converts succinate to fumarate and is involved in the electron transport chain. It produces FADH₂, not NADPH.
6. A newborn presents with acute respiratory distress, significant muscle issues, delayed development, and neurological concerns. Despite normal enzymatic levels in various metabolic pathways, there is a notable deficiency in acetyl-CoA carboxylase. This enzyme deficiency raises a diagnostic question about the underlying cause of the infant’s respiratory issues. What might be the most probable reason for the infant’s respiratory issues?
A. Hypoglycemia
B. Hypertriglyceridemia
C. Biotin deficiency
D. Metabolic acidosis
E. Hyperglycemia
Correct Answer: C. Biotin deficiency. Acetyl-CoA carboxylase (ACC) requires biotin as a cofactor to catalyze the conversion of acetyl-CoA to malonyl-CoA, the first committed step in fatty acid synthesis. Biotin deficiency can impair ACC activity, leading to inadequate fatty acid synthesis. Fatty acids are crucial for maintaining lung surfactant, which is essential for respiratory function. Therefore, a biotin deficiency could result in insufficient lung surfactant, contributing to respiratory distress in the newborn.
Incorrect Options:
A. Hypoglycemia: While hypoglycemia can cause neurological and developmental issues, it is not directly related to acetyl-CoA carboxylase activity or fatty acid synthesis. Hypoglycemia would also present with different metabolic findings.
B. Hypertriglyceridemia: This condition involves elevated triglyceride levels in the blood, which is not typically associated with a deficiency in acetyl-CoA carboxylase. In fact, deficient ACC activity would likely reduce fatty acid and triglyceride synthesis rather than increase it.
D. Metabolic acidosis: Metabolic acidosis might accompany certain metabolic disorders, but it is not directly associated with acetyl-CoA carboxylase deficiency. Additionally, metabolic acidosis would present with other specific findings, such as low blood pH and high lactate levels, which are not necessarily linked to surfactant deficiency.
E. Hyperglycemia: Elevated blood glucose (hyperglycemia) is not directly linked to acetyl-CoA carboxylase deficiency or respiratory distress. Hyperglycemia typically results from insulin issues and is unrelated to the surfactant production necessary for respiratory function.
7. A 30-year-old pregnant woman has a strong craving for sugar and consumes a hot fudge sundae. As her serum glucose levels rise, insulin is released, which increases the activity of acetyl-CoA carboxylase (ACC), the rate-limiting enzyme in fatty acid biosynthesis. Which of the following best describes this regulatory enzyme?
A. It is activated by carboxylation
B. It catalyzes a reaction that condenses an acetyl group with a malonyl group
C. It catalyzes a reaction that requires biotin and ATP
D. It converts malonyl-CoA to acetyl-CoA
E. It is activated by malonyl-CoA
Correct Answer: C. It catalyzes a reaction that requires biotin and ATP. Acetyl-CoA carboxylase (ACC) catalyzes the conversion of acetyl-CoA to malonyl-CoA, the first committed step in fatty acid synthesis. This reaction requires biotin as a cofactor and ATP for energy. Biotin serves as a carrier for the CO₂ group, which is added to acetyl-CoA to form malonyl-CoA. This reaction is crucial in initiating fatty acid biosynthesis.
Incorrect Options:
A. It is activated by carboxylation: ACC catalyzes a carboxylation reaction (adding CO₂ to acetyl-CoA to form malonyl-CoA), but the enzyme itself is not activated by carboxylation. ACC is regulated by polymerization (enhanced by citrate) and by phosphorylation/dephosphorylation rather than carboxylation.
B. It catalyzes a reaction that condenses an acetyl group with a malonyl group. This condensation step occurs later in fatty acid synthesis and is carried out by the enzyme fatty acid synthase (FAS), not ACC. ACC’s role is to produce malonyl-CoA, not to condense it with acetyl-CoA.
D. It converts malonyl-CoA to acetyl-CoA: ACC performs the opposite reaction; it converts acetyl-CoA into malonyl-CoA, not the other way around.
E. It is activated by malonyl-CoA: Malonyl-CoA is a product of the reaction catalyzed by ACC and does not activate the enzyme. In fact, high levels of malonyl-CoA can inhibit fatty acid oxidation by blocking carnitine palmitoyltransferase I (CPT I) but do not serve as an activator for ACC.
8. Which of the following mechanisms is involved in regulating the rate of fatty acid synthesis when a person consumes a low-carbohydrate diet for a prolonged period?
A. Allosteric modification
B. Covalent modification
C. Feedback inhibition
D. Reduced substrate concentration
E. Repression
Correct Answer: E. Repression. In a low-carbohydrate diet, the body decreases the expression of enzymes involved in fatty acid synthesis at the genetic level, a process known as repression. This occurs because low carbohydrate availability reduces insulin levels and increases glucagon, which signals the body to conserve energy and focus on fat oxidation rather than synthesis. This leads to decreased expression of key enzymes in fatty acid synthesis, such as acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS), thereby reducing the rate of fatty acid synthesis over time.
Incorrect Options:
A. Allosteric modification: Allosteric regulation, such as activation by citrate and inhibition by palmitoyl-CoA, is a mechanism of acute regulation but does not explain the long-term decrease in enzyme levels associated with a prolonged low-carbohydrate diet.
B. Covalent modification: Covalent modification, like phosphorylation and dephosphorylation of ACC, provides short-term regulation of enzyme activity in response to immediate needs. However, it does not account for the sustained decrease in enzyme synthesis over an extended period of low-carbohydrate intake.
C. Feedback inhibition: Feedback inhibition refers to the inhibition of an enzyme by its end product (e.g., fatty acids inhibiting ACC). While this mechanism does help regulate fatty acid synthesis, it is a short-term response and does not fully account for the long-term reduction in enzyme activity under low-carbohydrate dietary conditions.
D. Reduced substrate concentration: Although reduced availability of acetyl-CoA could influence fatty acid synthesis rates, substrate concentration alone does not fully account for the downregulation of fatty acid synthesis enzymes, which is driven more significantly by changes in enzyme expression.
9. It’s pivotal to understand the nuanced regulation mechanisms that prevent fatty acids, synthesized by the fatty acid synthase complex, from becoming substrates for beta-oxidation. Which of the following statements best explains why newly synthesized fatty acids are not immediate substrates for beta-oxidation?
A. Acetyl-CoA, the substrate for the fatty acid synthase complex, inhibits carnitine palmitoyltransferase-2
B. High glucagon causes phosphorylation of acetyl-CoA carboxylase whenever fatty acid synthase is active
C. High NADPH, a requirement for fatty acid synthesis, inhibits beta-oxidation
D. The product of the control step for fatty acid synthesis also inhibits carnitine palmitoyltransferase-1
Correct Answer: D. The product of the control step for fatty acid synthesis also inhibits carnitine palmitoyltransferase-1. The product of the control step in fatty acid synthesis is malonyl-CoA, which is formed by acetyl-CoA carboxylase (ACC). Malonyl-CoA serves as a potent inhibitor of carnitine palmitoyltransferase-1 (CPT-1), the enzyme responsible for transporting fatty acids into the mitochondria for beta-oxidation. By inhibiting CPT-1, malonyl-CoA prevents newly synthesized fatty acids from entering the mitochondria, thus blocking beta-oxidation and ensuring that fatty acids are stored or utilized for membrane synthesis rather than immediately oxidized.
Incorrect Options:
A. Acetyl-CoA, the substrate for the fatty acid synthase complex, inhibits carnitine palmitoyltransferase-2: Acetyl-CoA is indeed a substrate for fatty acid synthesis, but it does not directly inhibit carnitine palmitoyltransferase-2 (CPT-2). CPT-2 functions within the mitochondria and is not regulated by acetyl-CoA.
B. High glucagon causes phosphorylation of acetyl-CoA carboxylase whenever fatty acid synthase is active: Glucagon does lead to the phosphorylation (and inactivation) of acetyl-CoA carboxylase, which would decrease malonyl-CoA levels, promoting beta-oxidation. However, glucagon’s action typically opposes fatty acid synthesis rather than working simultaneously with it, so this is not a direct mechanism preventing the oxidation of newly synthesized fatty acids.
C. High NADPH, a requirement for fatty acid synthesis, inhibits beta-oxidation: While NADPH is essential for fatty acid synthesis, it does not inhibit beta-oxidation directly. NADPH is mainly involved in reductive biosynthesis and does not interact directly with the enzymes involved in beta-oxidation.
10. A 24-year-old male presents with fatigue and weight loss. Laboratory results indicate elevated levels of free fatty acids in the blood. A deficiency in which enzyme would most likely impair triglyceride synthesis, leading to increased free fatty acids in the bloodstream?
A. Acetyl-CoA carboxylase
B. Glycerol-3-phosphate acyltransferase
C. Hormone-sensitive lipase
D. Carnitine palmitoyltransferase I
E. Fatty acid synthase
Correct Answer: B. Glycerol-3-phosphate acyltransferase. This enzyme initiates triglyceride synthesis by attaching a fatty acid to glycerol-3-phosphate. A deficiency would prevent triglyceride formation, leading to an accumulation of free fatty acids.
Incorrect Options:
A. Acetyl-CoA carboxylase: This enzyme is involved in fatty acid synthesis, not triglyceride synthesis.
C. Hormone-sensitive lipase: This enzyme breaks down triglycerides into fatty acids and is not responsible for triglyceride synthesis.
D. Carnitine palmitoyltransferase I: This enzyme transports fatty acids into mitochondria for oxidation, unrelated to triglyceride formation.
E. Fatty acid synthase: This enzyme synthesizes fatty acids that are not directly involved in triglyceride synthesis.
11. A researcher studies a genetic mutation that reduces the activity of fatty acid synthase (FAS). Which of the following would most likely accumulate in the cytoplasm due to decreased FAS activity?
A. Acetyl-CoA
B. Malonyl-CoA
C. Citrate
D. Pyruvate
E. Oxaloacetate
Correct answer: B. Malonyl-CoA. Malonyl-CoA is a precursor in fatty acid synthesis. With reduced FAS activity, it would accumulate since it cannot be used for fatty acid chain elongation.
Incorrect Options:
A. Acetyl-CoA: Acetyl-CoA enters the pathway but is not directly accumulated due to FAS inhibition.
C. Citrate: Citrate is a precursor for acetyl-CoA, is not directly involved with FAS, and would not accumulate here.
D. Pyruvate: Pyruvate is involved in glycolysis, not directly in fatty acid synthesis.
E. Oxaloacetate: Oxaloacetate is part of the TCA cycle, not the fatty acid synthesis pathway.
12. A 28-year-old woman has been on a high-carbohydrate diet. Which molecule derived from glucose metabolism is most likely to activate acetyl-CoA carboxylase and thereby stimulate fatty acid synthesis?
A. Glucose 6-phosphate
B. Citrate
C. Pyruvate
D. Acetyl-CoA
E. Lactate
Correct answer: B. Citrate. Citrate activates acetyl-CoA carboxylase (ACC), enhancing fatty acid synthesis by promoting ACC polymerization.
Incorrect Options:
A. Glucose 6-phosphate: This molecule is part of glycolysis and the pentose phosphate pathway but does not activate ACC.
C. Pyruvate: Pyruvate is a product of glycolysis, not a direct activator of ACC.
D. Acetyl-CoA: Acetyl-CoA is a substrate for ACC but does not activate it.
E. Lactate: Lactate is a byproduct of anaerobic glycolysis, not involved in activating ACC.
13. A newborn has a metabolic disorder characterized by impaired synthesis of triglycerides. Which of the following molecules is essential for the initial step in triglyceride synthesis, by providing the backbone for fatty acid attachment?
A. Acetyl-CoA
B. Malonyl-CoA
C. Glycerol-3-phosphate
D. Pyruvate
E. Lactate
Correct Answer: C. Glycerol-3-phosphate. Glycerol-3-phosphate is the backbone molecule for triglyceride synthesis, allowing fatty acids to attach and form triglycerides.
Incorrect Options:
A. Acetyl-CoA: Acetyl-CoA is involved in fatty acid synthesis, not directly in triglyceride formation.
B. Malonyl-CoA: Malonyl-CoA is an intermediate in fatty acid synthesis, not a direct component of triglycerides.
D. Pyruvate: Pyruvate is a glycolysis product and is not involved in triglyceride synthesis.
E. Lactate: Lactate is a byproduct of anaerobic glycolysis and does not play a role in triglyceride synthesis.
14. A 16-year-old male with a rare genetic deficiency in fatty acid synthase (FAS) has trouble gaining weight and muscle mass. Which of the following is the most direct consequence of a deficiency in fatty acid synthase?
A. Decreased production of acetyl-CoA
B. Decreased levels of malonyl-CoA
C. Reduced synthesis of palmitate
D. Increased triglyceride formation
E. Elevated levels of free fatty acids
Correct Answer: C. Reduced synthesis of palmitate. Fatty acid synthase (FAS) is the enzyme complex responsible for synthesizing palmitate, a 16-carbon saturated fatty acid, from acetyl-CoA and malonyl-CoA. A deficiency in FAS would directly reduce the synthesis of palmitate and other long-chain fatty acids. Palmitate is crucial for energy storage and membrane synthesis, so a lack of FAS activity would impact the body’s ability to produce these fats, contributing to poor weight gain and development issues in the patient.
Incorrect Options:
A. Decreased production of acetyl-CoA: Acetyl-CoA production is not directly affected by FAS activity. Acetyl-CoA is generated from various sources, including glycolysis and beta-oxidation, and is the substrate used by FAS, not a product.
B. Decreased levels of malonyl-CoA: Malonyl-CoA is synthesized by acetyl-CoA carboxylase (ACC) and serves as a building block for fatty acid synthesis, but its production is independent of FAS. In fact, a deficiency in FAS might lead to an accumulation of malonyl-CoA due to reduced utilization.
D. Increased triglyceride formation: Triglyceride formation would likely decrease, not increase, because reduced palmitate production limits the availability of fatty acids needed for triglyceride synthesis.
E. Elevated levels of free fatty acids: Free fatty acids are typically sourced from triglyceride breakdown or dietary fats. A deficiency in FAS would not directly cause elevated levels of free fatty acids; instead, it would reduce the synthesis of new fatty acids, which could lead to fewer stored triglycerides.
15. A 40-year-old woman with a history of obesity is advised to follow a low-calorie diet to manage her weight. After several weeks on the diet, her body starts mobilizing stored fat as an energy source. Which of the following best explains why fatty acid synthesis is inhibited under these conditions?
A. Increased levels of malonyl-CoA
B. High insulin levels
C. Elevated activity of AMP-activated protein kinase (AMPK)
D. Increased NADPH availability
E. High levels of cytosolic citrate
Correct Answer: C. Elevated activity of AMP-activated protein kinase (AMPK). AMPK is activated in response to low cellular energy levels (high AMP/ATP ratio), which commonly occurs during calorie restriction or fasting. When activated, AMPK phosphorylates and inactivates acetyl-CoA carboxylase (ACC), the rate-limiting enzyme in fatty acid synthesis. This reduces the production of malonyl-CoA, thereby inhibiting fatty acid synthesis and favoring fat mobilization and oxidation for energy.
Incorrect Options:
A. Increased levels of malonyl-CoA: Malonyl-CoA is a product of ACC and is required for fatty acid synthesis. Elevated malonyl-CoA levels would activate fatty acid synthesis and inhibit beta-oxidation, the opposite of what occurs during calorie restriction.
B. High insulin levels: Insulin promotes fatty acid synthesis by activating ACC through dephosphorylation. Under low-calorie conditions, insulin levels decrease, favoring catabolic pathways rather than fatty acid synthesis.
D. Increased NADPH availability: NADPH is essential for fatty acid synthesis, providing reducing power for the anabolic reactions. During calorie restriction, NADPH availability may decrease, further limiting fatty acid synthesis.
E. High levels of cytosolic citrate: Citrate is an allosteric activator of ACC and promotes fatty acid synthesis. Under fasting or calorie restriction, cytosolic citrate levels typically decrease as citrate is directed into the TCA cycle for ATP production.
16. Which of the following is the primary role of NADPH in fatty acid synthesis?
A. Provides ATP for the condensation reaction
B. Serves as an energy substrate for the TCA cycle
C. Acts as a reducing agent in the chain elongation process
D. Inhibits acetyl-CoA carboxylase
E. Activates fatty acid synthase (FAS)
Correct Answer: C. Acts as a reducing agent in the chain elongation process. NADPH provides the reducing power needed for the reduction steps in fatty acid chain elongation, enabling the conversion of intermediates into fully saturated fatty acids.
Incorrect Options:
A. Provides ATP for the condensation reaction: ATP is not involved in the condensation reactions of fatty acid synthesis. ATP is used in the initial conversion of acetyl-CoA to malonyl-CoA, but NADPH’s role is specifically in reduction, not energy provision.
B. Serves as an energy substrate for the TCA cycle: NADPH does not participate in the TCA cycle, which primarily uses NADH and FADH₂ as electron carriers.
D. Inhibits acetyl-CoA carboxylase: NADPH does not inhibit acetyl-CoA carboxylase (ACC); instead, it provides reducing power for fatty acid synthesis downstream of ACC.
E. Activates fatty acid synthase (FAS): NADPH does not activate FAS; it acts as a coenzyme by donating electrons during the reduction steps of fatty acid elongation.
17. Which of the following pathways is the primary source of NADPH for fatty acid synthesis?
A. Glycolysis
B. Tricarboxylic acid (TCA) cycle
C. Pentose phosphate pathway (PPP)
D. Urea cycle
E. Beta-oxidation
Correct Answer: C. Pentose phosphate pathway (PPP). The PPP is the main source of NADPH in cells, as it generates NADPH during the oxidation of glucose-6-phosphate, which is essential for anabolic pathways like fatty acid synthesis.
Incorrect Options:
A. Glycolysis: Glycolysis primarily generates ATP and NADH, not NADPH.
B. Tricarboxylic acid (TCA) cycle: The TCA cycle generates NADH and FADH₂, which are used in the electron transport chain, not for anabolic processes.
D. Urea cycle: The urea cycle is involved in nitrogen disposal and does not produce NADPH.
E. Beta-oxidation: Beta-oxidation breaks down fatty acids and produces NADH and FADH₂ but does not produce NADPH.
18. During each cycle of fatty acid elongation, how many NADPH molecules are consumed?
A. 1
B. 2
C. 3
D. 4
E. 6
Correct Answer: B. 2. Each cycle of fatty acid synthesis requires two NADPH molecules, one for reducing the keto group to a hydroxyl group and another for reducing the double bond to a single bond.
Incorrect Options:
A. 1: This is incorrect; one NADPH is insufficient as two reduction steps occur per elongation cycle.
C. 3: Three NADPH molecules are not required per cycle; only two are used.
D. 4: Four NADPH molecules would exceed the actual requirement of two per cycle.
E. 6: Six NADPH molecules per cycle would be excessive; only two are needed for the two reduction steps.
19. Which of the following enzymes is involved in providing NADPH specifically for fatty acid synthesis by converting malate to pyruvate?
A. Glucose-6-phosphate dehydrogenase
B. Malic enzyme
C. Acetyl-CoA carboxylase
D. Pyruvate dehydrogenase
E. Isocitrate dehydrogenase
Correct Answer: B. Malic enzyme. The malic enzyme converts malate to pyruvate and produces NADPH as a byproduct, which is used in fatty acid synthesis.
Incorrect Options:
A. Glucose-6-phosphate dehydrogenase: While this enzyme does produce NADPH, it functions in the pentose phosphate pathway, not in converting malate to pyruvate.
C. Acetyl-CoA carboxylase: Acetyl-CoA carboxylase (ACC) is involved in producing malonyl-CoA, not NADPH production.
D. Pyruvate dehydrogenase: This enzyme converts pyruvate to acetyl-CoA, but it produces NADH, not NADPH.
E. Isocitrate dehydrogenase: This enzyme produces NADH (or NADPH in some cases) in the TCA cycle, but it does not provide NADPH for fatty acid synthesis directly.
20. In fatty acid synthesis, NADPH is used directly by which of the following enzyme complexes?
A. Fatty acid synthase (FAS)
B. Acetyl-CoA carboxylase
C. Pyruvate carboxylase
D. Glucose-6-phosphate dehydrogenase
E. Carnitine palmitoyltransferase I
Correct Answer: A. Fatty acid synthase (FAS). FAS is the enzyme complex that catalyzes fatty acid chain elongation. It requires NADPH for the reduction reactions that occur within each elongation cycle.
Incorrect Options:
B. Acetyl-CoA carboxylase: ACC catalyzes the conversion of acetyl-CoA to malonyl-CoA but does not directly use NADPH.
C. Pyruvate carboxylase: Pyruvate carboxylase is involved in gluconeogenesis, using biotin as a cofactor, not NADPH.
D. Glucose-6-phosphate dehydrogenase: This enzyme produces NADPH in the pentose phosphate pathway but does not use it.
E. Carnitine palmitoyltransferase I: CPT-I is involved in transporting fatty acids into mitochondria for oxidation, not in fatty acid synthesis or NADPH utilization.
21. Why is NADPH essential in fatty acid synthesis instead of NADH?
A. NADPH is a more potent energy carrier
B. NADPH is specifically produced in the cytoplasm
C. NADH inhibits acetyl-CoA carboxylase
D. NADPH is selectively used in biosynthetic pathways
E. NADH is unstable in fatty acid synthesis
Correct Answer: D. NADPH is selectively used in biosynthetic pathways. NADPH is preferentially used in anabolic reactions, like fatty acid and cholesterol synthesis, providing the necessary reducing power. NADH, on the other hand, is mainly used in catabolic reactions like ATP production.
Incorrect Options:
A. NADPH is a more potent energy carrier: This is not true; both NADPH and NADH carry electrons, but their roles are distinct due to their cellular compartmentalization and function.
B. NADPH is specifically produced in the cytoplasm: While NADPH is produced in the cytoplasm, NADH can also be present there. The distinction is in their roles, not just their location.
C. NADH inhibits acetyl-CoA carboxylase: NADH does not inhibit ACC; malonyl-CoA or AMP indirectly regulate ACC activity.
E. NADH is unstable in fatty acid synthesis: This is incorrect. NADH is stable but is preferentially used in catabolic reactions rather than in biosynthesis.
22. Which condition would lead to increased NADPH requirements for fatty acid synthesis in liver cells?
A. Prolonged fasting
B. High-carbohydrate diet
C. Low insulin levels
D. Elevated glucagon
E. Increased beta-oxidation
Correct Answer: B. High-carbohydrate diet. A high-carbohydrate diet increases glucose availability, leading to more glucose being shunted through glycolysis and the pentose phosphate pathway (PPP). The PPP generates NADPH, which is essential for fatty acid synthesis. Increased glucose metabolism raises citrate levels, which activates acetyl-CoA carboxylase (ACC), promoting fatty acid synthesis and subsequently increasing NADPH requirements to support the reductive steps of this pathway.
Incorrect Options:
A. Prolonged fasting: During fasting, the body shifts towards fatty acid oxidation and ketone body production rather than fatty acid synthesis, reducing the demand for NADPH in the liver.
C. Low insulin levels: Low insulin levels reduce fatty acid synthesis because insulin normally promotes ACC activation. Therefore, NADPH requirements would decrease in the liver under low insulin conditions.
D. Elevated glucagon: High glucagon levels activate AMP-activated protein kinase (AMPK), which inactivates ACC, reducing fatty acid synthesis and NADPH demand.
E. Increased beta-oxidation: During beta-oxidation, fatty acids are broken down for energy and not synthesized. Beta-oxidation requires NAD+ and FAD, not NADPH, so the demand for NADPH would decrease.
