1. A 45-year-old patient presents to the clinic with significant weight loss and fatigue. Blood tests reveal elevated levels of epinephrine and glucagon. Given this clinical context, when these hormones bind to receptors on the adipose cell membrane, which of the following is NOT expected to occur?
A. Fatty acids are activated, enter the mitochondria, and are oxidized by beta-oxidation and the TCA cycle
B. Free fatty acids are carried to most tissues of the body by albumin
C. Increased beta-oxidation increases glycolysis in resting muscle
D. The cAMP cascade activates hormone-sensitive lipase
E. Triacylglycerol is hydrolyzed to free fatty acids, and glycerol
Explanations:
Correct Answer: C. Increased beta-oxidation increases glycolysis in resting muscle. This statement is incorrect. In a clinical scenario where epinephrine or glucagon levels are elevated, the body shifts to using fatty acids as the primary energy source, resulting in decreased glycolysis in resting muscle. The activation of beta-oxidation indicates a preference for fatty acid metabolism over glucose utilization.
Incorrect Options:
A. Fatty acids are activated, enter the mitochondria, and are oxidized by beta-oxidation and the TCA cycle. This is correct and expected. Elevated levels of epinephrine or glucagon stimulate pathways that mobilize fatty acids for energy production through beta-oxidation and subsequent oxidation in the TCA cycle.
B. Free fatty acids are carried to most tissues of the body by albumin: This is correct and expected. When triacylglycerols are hydrolyzed in response to high levels of epinephrine or glucagon, free fatty acids are released into the bloodstream and transported by albumin to other tissues for energy use.
D. The cAMP cascade activates hormone-sensitive lipase: This is correct and expected. The activation of the cAMP cascade by epinephrine or glucagon leads to the activation of hormone-sensitive lipase, which facilitates the breakdown of stored triacylglycerol.
E. Triacylglycerol is hydrolyzed to free fatty acids and glycerol: This is correct and expected. The activation of hormone-sensitive lipase results in the hydrolysis of triacylglycerol, releasing free fatty acids and glycerol into the bloodstream for energy production.
2. A 16-year-old girl, presenting with a body weight 35% below the expected range and perceiving herself as obese despite her extreme slenderness, rigorously limits her food intake and is diagnosed with Anorexia Nervosa. Given her inadequate dietary intake, the breakdown of fatty acids becomes imperative to furnish energy. Which substance is generated in the initial step of fatty acid beta-oxidation?
A. ATP
B. Carnitine
C. CoASH
D. Fatty acyl CoA
E. Malonyl CoA
Explanations:
Correct Answer: D. Fatty acyl CoA. In the initial step of fatty acid beta-oxidation, fatty acids in the cytosol are activated by the enzyme acyl-CoA synthetase (also known as fatty acid thiokinase). This activation step converts the free fatty acid into fatty acyl CoA, preparing it for transport into the mitochondria for subsequent beta-oxidation.
Incorrect Options:
A. ATP: While ATP is used in the activation process of fatty acids (it is converted to AMP and pyrophosphate), it is not generated in the initial step of beta-oxidation. Instead, it is consumed during the conversion of the free fatty acid to fatty acyl CoA.
B. Carnitine: Carnitine plays a role in transporting fatty acyl CoA across the mitochondrial membrane by forming fatty acyl-carnitine but is not generated in the initial step of beta-oxidation itself.
C. CoASH: CoASH (coenzyme A) is part of the reaction to form fatty acyl CoA, as it combines with the fatty acid, but it is not the primary product of the initial step.
E. Malonyl CoA: Malonyl CoA is involved in fatty acid synthesis, not in beta-oxidation. It is an intermediate in the biosynthesis pathway and also serves as an inhibitor of carnitine palmitoyltransferase I (CPT I), preventing the transport of fatty acyl CoA into the mitochondria during fatty acid synthesis.
3. A 50-year-old man with a history of metabolic syndrome presents to the clinic for routine evaluation. He reports a recent change in diet and an increase in body weight due to a high intake of carbohydrates. Blood tests reveal elevated levels of triglycerides. During active fatty acid synthesis in the liver, a concurrent decrease in beta-oxidation of fatty acids is observed. What is the reason for this decline in beta-oxidation?
A. Decrease in adipolysis
B. Inhibition by end-product
C. Decreased availability of ATP
D. Inhibition of translocation between cellular compartments
E. Inactivation of specific enzymes of fatty acid oxidation
Explanations:
Correct Answer: D. Inhibition of translocation between cellular compartments. During active fatty acid synthesis, the key reason for the decrease in beta-oxidation is the inhibition of the transport of fatty acyl CoA into the mitochondria. Malonyl CoA, a product of the initial steps of fatty acid synthesis, acts as an inhibitor of carnitine palmitoyltransferase I (CPT I), the enzyme responsible for transferring fatty acyl CoA into the mitochondria for beta-oxidation. This regulation ensures that the liver does not simultaneously synthesize and break down fatty acids, maintaining metabolic balance.
Incorrect Options:
A. Decrease in adipolysis: Adipolysis refers to the breakdown of fat in adipose tissue. While reduced adipolysis could affect the overall supply of fatty acids, it is not the direct mechanism leading to a decline in beta-oxidation during active liver fatty acid synthesis.
B. Inhibition by end-product: This option would imply feedback inhibition by a final product. Although feedback regulation exists in many pathways, it is not the reason for the suppression of beta-oxidation during fatty acid synthesis in this context.
C. Decreased availability of ATP: ATP availability would generally promote beta-oxidation, if low, to meet energy demands. Thus, this is not relevant to the observed decrease in beta-oxidation during active synthesis.
E. Inactivation of specific enzymes of fatty acid oxidation: The decline in beta-oxidation is not due to the inactivation of enzymes but rather the inhibition of the transport of fatty acids into the mitochondria.
4. A 10-year-old girl, experiencing difficulty walking, muscle weakness, and altered mental status is diagnosed with carnitine acyltransferase deficiency. Which of the following is produced in the reaction catalyzed by Carnitine Acyltransferase-I (CAT-I)?
A. β-Keto acyl CoA
B. β-OH-Acyl CoA
C. Fatty acylcarnitine
D. Fatty acyl CoA
E. Fatty enoyl CoA
Explanations:
Correct Answer: C. Fatty acyl carnitine. Carnitine Acyltransferase-I (CAT-I) catalyzes the transfer of the fatty acyl group from fatty acyl CoA to carnitine, forming fatty acylcarnitine. This reaction is crucial for the transport of long-chain fatty acids from the cytosol into the mitochondria, where they undergo beta-oxidation.
Incorrect Options:
A. β-Keto acyl CoA: This is an intermediate formed during the beta-oxidation cycle, not during the action of CAT-I. It is not the product of the reaction catalyzed by CAT-I.
B. β-OH-Acyl CoA: This is also an intermediate in the beta-oxidation pathway, produced during the second step of the cycle. It is not produced by CAT-I.
D. Fatty acyl CoA: This is the substrate for CAT-I, not the product. CAT-I uses fatty acyl CoA to produce fatty acylcarnitine.
E. Fatty enoyl CoA: This is another intermediate in the beta-oxidation cycle that forms after the initial dehydrogenation step, not in the reaction catalyzed by CAT-I.
5. A 12-year-old boy presents with recurrent episodes of muscle pain, weakness, and dark urine after prolonged exercise or periods of fasting. He is diagnosed with Carnitine Acyltransferase-II (CAT-II) deficiency. Which of the following processes is directly impaired due to the enzyme’s dysfunction?
A. Formation of fatty acylcarnitine in the cytosol
B. Conversion of fatty acylcarnitine to fatty acyl CoA in the mitochondria
C. Degradation of fatty acyl CoA into acetyl CoA
D. Activation of fatty acids to form fatty acyl CoA
E. Transport of carnitine out of the mitochondria
Explanations:
Correct Answer: B. Conversion of fatty acylcarnitine to fatty acyl CoA in the mitochondria. Carnitine Acyltransferase-II (CAT-II) is responsible for converting fatty acyl carnitine back into fatty acyl CoA inside the mitochondria, allowing the fatty acid to proceed to beta-oxidation. Deficiency in CAT-II leads to impaired energy production, especially during periods of fasting or extended physical activity.
Incorrect Options:
A. Formation of fatty acylcarnitine in the cytosol: This process is catalyzed by Carnitine Acyltransferase-I (CAT-I), which is located on the outer mitochondrial membrane. CAT-I converts fatty acyl CoA to fatty acyl carnitine to facilitate its transport into the mitochondria. This step is unaffected in CAT-II deficiency, as CAT-I operates before CAT-II in the transport pathway.
C. Degradation of fatty acyl CoA into acetyl CoA: This process occurs during beta-oxidation inside the mitochondria. Once fatty acyl CoA is present, it undergoes a series of reactions to produce acetyl CoA, which then enters the TCA cycle for energy production. CAT-II deficiency impairs the formation of fatty acyl CoA from fatty acyl carnitine but does not directly involve the degradation step itself.
D. Activation of fatty acids to form fatty acyl CoA: This step occurs in the cytosol and is catalyzed by acyl-CoA synthetase (also known as fatty acid thiokinase). This enzyme converts free fatty acids into fatty acyl CoA before they are transported into the mitochondria. CAT-II deficiency does not affect this activation step, as it occurs upstream of CAT-II’s function.
E. Transport of carnitine out of the mitochondria: The transport of carnitine back to the cytosol is mediated by the carnitine/acylcarnitine translocase (CACT). CAT-II converts fatty acyl carnitine into fatty acyl CoA in the mitochondria, freeing carnitine to be recycled and transported back to the cytosol. CAT-II deficiency does not impair the transport of carnitine itself but rather the conversion step, preventing efficient fatty acid utilization.
6. During fasting or exercise, fatty acids must enter the mitochondria for oxidation. Which of the following factors inhibits this entry?
A. Active protein kinase A
B. AMP
C. Epinephrine
D. Glucagon
E. Insulin
Explanations:
Correct Answer: E. Insulin. Insulin promotes fatty acid synthesis and inhibits fatty acid oxidation by increasing the levels of malonyl-CoA, which acts as an inhibitor of Carnitine Palmitoyltransferase I (CPT-I), the enzyme responsible for transporting fatty acyl CoA into the mitochondria. Thus, insulin effectively prevents fatty acids from entering the mitochondria for oxidation.
Incorrect Options:
A. Active protein kinase A: Active protein kinase A (PKA) is stimulated by hormones like glucagon and epinephrine. It promotes lipolysis and enhances the mobilization of fatty acids for oxidation. It does not inhibit the entry of fatty acids into the mitochondria.
B. AMP: AMP is an indicator of low energy status in the cell and activates AMP-activated protein kinase (AMPK). AMPK reduces the synthesis of malonyl-CoA and promotes fatty acid oxidation by removing inhibition from CPT-I. It facilitates, rather than inhibits, fatty acid entry into the mitochondria.
C. Epinephrine: Epinephrine activates lipolysis and stimulates pathways that increase the availability of free fatty acids for oxidation. It does not inhibit fatty acid entry into the mitochondria; instead, it helps mobilize and utilize them for energy.
D. Glucagon: Glucagon triggers pathways that enhance fatty acid oxidation by activating PKA, which supports the breakdown of stored fat and reduces malonyl-CoA synthesis. This facilitates, rather than inhibits, fatty acid entry into the mitochondria.
7. An infant exhibiting lethargy, sweating, and irritability is admitted to the Pediatrics unit. Notably, his symptoms intensify when feeding is delayed. After comprehensive testing, a diagnosis indicates a deficiency in an enzyme catalyzing the first step of the β-oxidation spiral. Identify the enzyme:
A. Acyl CoA dehydrogenase
B. Beta hydroxy acyl-CoA dehydrogenase
C. Enoyl CoA reductase
D. Fatty acid synthase
E. Thiolase
Explanations:
Correct Answer: A. Acyl CoA dehydrogenase. This enzyme catalyzes the first step of the β-oxidation spiral, which involves the dehydrogenation of fatty acyl CoA to produce trans-enoyl CoA. Deficiency in this enzyme, particularly medium-chain acyl-CoA dehydrogenase (MCAD) deficiency, can lead to severe hypoglycemia, lethargy, and other metabolic crises, especially during fasting or periods of low energy intake.
Incorrect Options:
B. Beta hydroxy acyl-CoA dehydrogenase: This enzyme catalyzes the third step of the β-oxidation spiral, converting β-hydroxy acyl-CoA to β-ketoacyl CoA. While important in the β-oxidation process, it does not catalyze the initial step and is not related to the immediate clinical findings associated with the first enzyme deficiency.
C. Enoyl CoA reductase: This enzyme is involved in the fatty acid synthesis pathway, not β-oxidation. It is responsible for reducing double bonds during fatty acid chain elongation. It is unrelated to the deficiency causing the symptoms described.
D. Fatty acid synthase: Fatty acid synthase is involved in the synthesis of fatty acids rather than their oxidation. It catalyzes the formation of palmitate from acetyl-CoA and malonyl-CoA and plays no role in the β-oxidation spiral.
E. Thiolase: Thiolase catalyzes the last step of the β-oxidation spiral, where it cleaves β-ketoacyl CoA to produce acetyl-CoA. While crucial for β-oxidation, it does not catalyze the first step, making it an incorrect answer for this scenario.
8. A 25-year-old marathon runner experiences severe fatigue, muscle cramping, and low energy levels after a race. Lab results indicate a deficiency in the enzyme responsible for the final step of the β-oxidation cycle. Which of the following processes would be impaired as a result of deficiency of this enzyme?
A. Release of acetyl-CoA from β-ketoacyl-CoA
B. Addition of water to enoyl-CoA
C. Oxidation of fatty acyl CoA to form trans-enoyl CoA
D. Reduction of NAD+ to NADH during oxidation
E. Transport of fatty acyl carnitine into the mitochondria
Explanations:
Correct Answer: A. Release of acetyl-CoA from β-ketoacyl-CoA. The enzyme responsible for the final step of the β-oxidation cycle is thiolase, which cleaves the bond between the α- and β-carbons of β-ketoacyl-CoA to release acetyl-CoA and a shortened fatty acyl-CoA. A deficiency in this enzyme would impair the release of acetyl-CoA, hindering energy production and the continuation of the β-oxidation cycle.
Incorrect Options:
B. Addition of water to enoyl-CoA: This process is performed by enoyl-CoA hydratase during the second step of β-oxidation, not by thiolase. A deficiency in thiolase would not affect this step.
C. Oxidation of fatty acyl CoA to form trans-enoyl CoA: This is the first step of β-oxidation, catalyzed by acyl-CoA dehydrogenase, which generates FADH2. Thiolase is not involved in this step.
D. Reduction of NAD+ to NADH during oxidation: This step is carried out by β-hydroxyacyl-CoA dehydrogenase in the third step of β-oxidation. Thiolase deficiency would not impact this part of the process.
E. Transport of fatty acyl carnitine into the mitochondria: This process is mediated by carnitine palmitoyltransferase I (CPT-I) and carnitine/acylcarnitine translocase (CACT), part of the carnitine shuttle. Thiolase plays no role in the transport of fatty acylcarnitine.
9. A 40-year-old woman, recently having undergone gastric bypass surgery, presents with severe vomiting attributed to the rapid consumption of large food quantities—a practice contraindicated post-surgery. Having successfully lost 10 lbs over the past month due to the mobilization of fat stores for acetyl CoA and energy production, a question arises: How many acetyl CoA molecules are produced upon the oxidation of palmitoyl CoA?
A. 2
B. 6
C. 8
D. 10
E. 12
Explanations:
Correct Answer: C. 8. Palmitoyl CoA, derived from palmitic acid (a 16-carbon fatty acid), undergoes β-oxidation, which involves sequential cleavage of 2-carbon units in the form of acetyl CoA. For a 16-carbon chain:
• Total Acetyl CoA Produced: Each cycle of β-oxidation produces one acetyl CoA, and since each cycle removes 2 carbon atoms, palmitoyl CoA completes 7 cycles of β-oxidation, yielding 7 acetyl CoA directly from these cycles. The final cleavage produces an additional 1 acetyl CoA molecule.
• Total Acetyl CoA Molecules: 8 acetyl CoA molecules are produced in total.
Incorrect Options:
A. 2: This is incorrect, as only 2 acetyl CoA molecules would be produced from a 4-carbon fatty acid like butyryl CoA, not palmitoyl CoA.
B. 6: This number would correspond to a shorter fatty acid, such as a 12-carbon fatty acid.
D. 10: This could suggest a larger fatty acid with more carbons, such as an 18-carbon fatty acid.
E. 12: This would imply a significantly longer fatty acid chain, such as a 24-carbon fatty acid, undergoing β-oxidation.
10. In one turn of the β-oxidation spiral, how many ATPs are produced by oxidative phosphorylation?
A. 0
B. 1
C. 2
D. 3
E. 4
Explanations:
Correct Answer: E. 4
In one turn of the β-oxidation spiral, the following are produced:
• 1 FADH2, which yields approximately 1.5 ATP through oxidative phosphorylation.
• 1 NADH, which yields approximately 2.5 ATP through oxidative phosphorylation.
Total ATP Yield:
• 1.5 ATP (from FADH2) + 2.5 ATP (from NADH) = 4 ATP per cycle of β-oxidation.
Incorrect Options:
A. 0: This is incorrect, as β-oxidation directly produces reducing equivalents (FADH2 and NADH), which generate ATP through oxidative phosphorylation.
B. 1: This underestimates the ATP produced, as one turn of β-oxidation generates more than just 1 ATP.
C. 2: This also underestimates the ATP yield, accounting for only one of the reducing equivalents.
D. 3: While closer to the actual number, it still falls short of the total ATP produced from one FADH2 and one NADH.
