Lipid Metabolism (Fatty Acid Synthesis and Oxidation, Lipoproteins, Cholesterol) MCQs

Biochemistry · 79 free questions with answers & explanations.

1. A 45-year-old man with familial hypercholesterolemia has xanthomas and a markedly elevated LDL. He is started on a statin. The primary mechanism by which statins lower plasma LDL is:
2. A patient with uncontrolled type 1 diabetes presents with markedly elevated plasma triglycerides and eruptive xanthomas. Lipoprotein lipase activity in post-heparin plasma is severely reduced. Which lipoprotein accumulates most prominently?
3. Fatty acid synthesis occurs in the cytosol of hepatocytes. The committed, rate-limiting step is catalyzed by acetyl-CoA carboxylase (ACC). Which molecule is the direct product of the ACC reaction?
4. A 52-year-old woman with type 2 diabetes and obesity has steatohepatitis on liver biopsy. Her fasting insulin is markedly elevated. The most significant biochemical consequence of chronic hyperinsulinemia on hepatic lipid metabolism is:
5. Beta-oxidation of a C18:0 (stearic acid, fully saturated) fatty acyl-CoA molecule yields how many acetyl-CoA molecules?
6. A patient with recurrent pancreatitis and eruptive xanthomata has fasting triglycerides of 4500 mg/dL. Lipoprotein electrophoresis shows a creamy supernatant layer with no clear plasma. LPL activity in post-heparin plasma is markedly reduced. The primary metabolic defect is impaired hydrolysis of triglycerides in which lipoprotein?
7. A 45-year-old woman with corneal arcus, tendon xanthomata, and premature coronary artery disease has LDL-C of 380 mg/dL despite a normal-weight body mass index. Genetic analysis reveals a gain-of-function mutation in PCSK9. The pathophysiology involves:
8. During prolonged fasting, hepatic fatty acid oxidation increases dramatically. The rate-limiting step of mitochondrial beta-oxidation entry is regulated by malonyl-CoA levels. In the fasted state, which metabolic change correctly describes this regulatory mechanism?
9. A 35-year-old man with abetalipoproteinemia (Bassen-Kornzweig syndrome) presents with steatorrhea, ataxia, retinitis pigmentosa, and acanthocytosis. The fundamental metabolic defect in this disorder is mutation in:
10. In cholesterol biosynthesis, statins inhibit HMG-CoA reductase, the rate-controlling enzyme. Following statin therapy, the compensatory upregulation of LDL receptors in hepatocytes is mediated by which molecular mechanism?
11. Acetyl-CoA carboxylase (ACC), the rate-limiting enzyme of fatty acid synthesis, is regulated at multiple levels. A drug that mimics the effect of glucagon on hepatic ACC would have which mechanism of action?
12. A patient has severely elevated plasma triglycerides (>2000 mg/dL), eruptive xanthomas, recurrent pancreatitis, and creamy plasma on refrigeration. Lipoprotein lipase (LPL) activity in post-heparin plasma is absent. Which lipoprotein class is most elevated, and why does HDL remain paradoxically low?
13. Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is the most common inherited fatty acid oxidation disorder. A child presents with hypoketotic hypoglycemia during a febrile illness. Why is ketogenesis specifically impaired despite increased fatty acid mobilization?
14. Statins inhibit HMG-CoA reductase, reducing cholesterol synthesis. Which compensatory cellular response limits the efficacy of low-dose statin monotherapy?
15. A patient with abetalipoproteinemia (MTP — microsomal triglyceride transfer protein deficiency) presents with fat malabsorption, acanthocytosis, spinocerebellar degeneration, and pigmentary retinopathy. Why do fat-soluble vitamin deficiencies dominate the neurological picture despite normal dietary intake?
16. A 35-year-old man with familial hypercholesterolemia undergoes genetic testing. The mutation is identified in the PCSK9 gene causing a gain-of-function variant. PCSK9 promotes LDL receptor degradation by binding the receptor after LDL dissociation. A new monoclonal antibody (evolocumab) neutralizes circulating PCSK9. By which mechanism does PCSK9 normally prevent LDL receptor recycling?
17. A patient with abdominal obesity, hypertriglyceridemia (TG 450 mg/dL), and low HDL is found to have reduced lipoprotein lipase (LPL) activity. LPL requires apolipoprotein C-II (apoC-II) as an activator. ApoC-II is carried primarily on HDL and transferred to chylomicrons and VLDL in the circulation. A patient with which genetic defect would have a phenotype indistinguishable from LPL deficiency?
18. In peroxisomal beta-oxidation, very long chain fatty acids (VLCFAs, >C22) are oxidized by a distinct mechanism. A patient with Zellweger syndrome has absent peroxisomes and accumulates VLCFAs. Unlike mitochondrial beta-oxidation, the first oxidation step in peroxisomal beta-oxidation uses which electron acceptor?
19. A 45-year-old woman with xanthelasma and corneal arcus has a fasting lipid profile showing: total cholesterol 320 mg/dL, LDL 260 mg/dL, HDL 55 mg/dL, TG 25 mg/dL. Her heterozygous sibling has LDL of 250 mg/dL. The defect is in the LDL receptor gene causing absent receptor protein. Treatment with rosuvastatin increases LDL receptor expression. Why is statin therapy partially effective in receptor-negative (null allele) familial hypercholesterolemia heterozygotes compared to homozygotes?
20. Malonyl-CoA inhibits carnitine palmitoyltransferase-1 (CPT-1) to prevent futile cycling between fatty acid synthesis and oxidation. In the fed state, elevated malonyl-CoA inhibits CPT-1, blocking fatty acid entry into mitochondria. In which intracellular location is the carnitine shuttle system blocked by malonyl-CoA?
21. A 6-month-old infant presents with hypotonia, cardiomyopathy, and muscle weakness. Urine organic acids show elevated C8–C14 acylcarnitines. The enzyme defect is:
22. Malonyl-CoA is a potent inhibitor of which enzyme, thereby coordinating de novo fatty acid synthesis with mitochondrial beta-oxidation to prevent a futile cycle?
23. A 35-year-old man with tendon xanthomas, corneal arcus, and premature coronary artery disease has LDL-cholesterol of 580 mg/dL. His father died of MI at age 42. The most likely molecular defect is:
24. A patient is started on a statin for hyperlipidemia. The primary biochemical mechanism involves competitive inhibition of HMG-CoA reductase, which leads to compensatory upregulation of hepatic LDL receptors. At which subcellular site does HMG-CoA reductase primarily reside, and what signals its degradation?
25. Tangier disease is characterized by nearly absent plasma HDL, cholesterol ester deposition in tonsils and cornea, and premature atherosclerosis. The defective gene encodes:
26. A 45-year-old man with type 2 diabetes and hypertriglyceridemia has markedly elevated VLDL and chylomicrons on lipoprotein electrophoresis (type V pattern). Lipoprotein lipase activity measured in post-heparin plasma is negligible. Which apolipoprotein is necessary for the activation of lipoprotein lipase at the capillary endothelium?
27. In fatty acid beta-oxidation, the very first step after acyl-CoA entry into the mitochondria is catalyzed by acyl-CoA dehydrogenase. Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is the most common inherited fatty acid oxidation disorder. Which metabolite accumulates and is detected on newborn screening?
28. HMG-CoA reductase catalyzes the rate-limiting step in cholesterol biosynthesis. Its activity is regulated at multiple levels. Which of the following represents post-translational regulation of this enzyme?
29. A 55-year-old woman with xanthomas and a strong family history of premature coronary artery disease has total cholesterol of 400 mg/dL and LDL of 330 mg/dL. Genetic testing confirms a point mutation in the LDL receptor gene. In familial hypercholesterolemia, which step in LDL receptor cycling is most commonly defective?
30. Malonyl-CoA acts as a metabolic signal that coordinates fatty acid synthesis and oxidation. How does malonyl-CoA prevent futile cycling during active fatty acid synthesis?
31. A male child presents with progressive skeletal myopathy, episodes of hypoketotic hypoglycemia, and cardiomyopathy, worsened by fasting. Plasma carnitine is very low. Urine organic acids show minimal ketones but elevated dicarboxylic acids. The likely diagnosis is:
32. A 10-year-old boy with recurrent pancreatitis has triglycerides >10,000 mg/dL, eruptive xanthomas, and lipemia retinalis. Apolipoprotein C-II levels are undetectable. Lipoprotein lipase (LPL) activity measured in post-heparin plasma is absent after addition of normal plasma. This confirms deficiency of:
33. The committed step in cholesterol biosynthesis is catalysed by HMG-CoA reductase. Statins competitively inhibit this enzyme. Which downstream effect is responsible for the greatest increase in LDL receptor expression following statin therapy?
34. In fatty acid synthesis, each two-carbon addition requires NADPH. Malonyl-CoA, the two-carbon donor, is formed from acetyl-CoA and CO2. The rate-limiting enzyme acetyl-CoA carboxylase is allosterically regulated. Which combination correctly identifies its allosteric activator and inhibitor?
35. Reverse cholesterol transport is the process by which peripheral cholesterol is delivered to the liver for excretion. Which plasma enzyme is essential for the maturation of nascent HDL (disc-shaped) to spherical mature HDL by esterifying cholesterol in the HDL particle?
36. A 2-year-old presents with hypotonia, hypoketotic hypoglycemia, elevated plasma C8 and C10 acylcarnitines, and sudden cardiac arrest during a febrile illness. The most likely deficient enzyme is:
37. Malonyl-CoA inhibits carnitine palmitoyltransferase I (CPT-I). What is the physiological significance of this in the post-prandial (fed) state in liver?
38. Abetalipoproteinemia (Bassen-Kornzweig syndrome) results from deficiency of microsomal triglyceride transfer protein (MTP). Which lipoprotein particles are absent in plasma?
39. A patient with homozygous familial hypercholesterolemia (HoFH) fails to respond to high-dose statins because:
40. Which step in the reverse cholesterol transport pathway requires lecithin:cholesterol acyltransferase (LCAT) activity?
41. A patient with type IIb hyperlipidemia (elevated LDL and VLDL) is started on a statin. The mechanism by which statins increase LDL receptor expression involves:
42. A 45-year-old man with type 2 diabetes has elevated triglycerides and reduced HDL. Lipoprotein lipase activity on chylomicrons and VLDL is decreased due to insulin deficiency. The apolipoprotein that functions as the obligate activator of lipoprotein lipase (LPL) on chylomicrons is:
43. During prolonged starvation, the liver switches from glucose oxidation to fatty acid oxidation. The key regulatory molecule that signals high beta-oxidation flux and inhibits malonyl-CoA synthesis (thereby preventing futile cycling) is:
44. A patient is found to have absent apolipoprotein B in plasma and steatorrhea from birth. Neurological symptoms (ataxia, peripheral neuropathy) develop in childhood despite normal dietary fat intake. This is abetalipoproteinemia. The primary defect is in which protein?
45. In the lipoprotein lipase (LPL) pathway, which apolipoprotein is essential for LPL activation, and what is the clinical consequence of its deficiency?
46. Cholesterol synthesis is regulated at the HMG-CoA reductase step. Which post-translational mechanism rapidly reduces HMG-CoA reductase activity in response to high intracellular sterol levels?
47. A patient with abdominal pain and eruptive xanthomas has triglycerides of 4500 mg/dL. LPL assay shows absent activity. Which lipoprotein accumulates in type I hyperlipoproteinemia (familial LPL deficiency)?
48. In the fasted state, hepatic ketogenesis is activated. Which enzyme controls the committed step of ketogenesis, and what regulates its activity?
49. Reverse cholesterol transport (RCT) is the mechanism by which peripheral cholesterol is returned to the liver. Which enzyme esterifies cholesterol on HDL during RCT, and what is its significance?
50. Familial hypercholesterolemia (FH) is caused by LDL receptor mutations. Which category of LDL receptor mutation results in the most severe phenotype (homozygous FH with cholesterol >600 mg/dL)?
51. During fatty acid oxidation, propionyl-CoA is generated from odd-chain fatty acids. The conversion of propionyl-CoA to succinyl-CoA requires two enzymatic steps. The second step (methylmalonyl-CoA mutase) requires which cofactor?
52. Abetalipoproteinaemia (Bassen-Kornzweig syndrome) is caused by a defect in MTP (microsomal triglyceride transfer protein). The consequence is inability to assemble:
53. PCSK9 (proprotein convertase subtilisin/kexin type 9) regulates LDL receptor levels. The mechanism by which PCSK9 inhibition lowers LDL-C is:
54. Statins inhibit HMG-CoA reductase, but upregulate LDL receptors. The mechanism linking HMG-CoA reductase inhibition to LDL receptor upregulation is:
55. Familial hypercholesterolaemia (FH) is caused by LDL receptor mutations. Which LDL receptor mutation class would result in receptor synthesis but failure to transport to cell surface?
56. Statins inhibit HMG-CoA reductase. Apart from reducing cholesterol synthesis, the indirect cellular consequence that paradoxically upregulates LDL receptor expression is:
57. Carnitine acylcarnitine translocase (CACT) deficiency presents as neonatal hypoketotic hypoglycaemia with hyperammonaemia. This enzyme deficiency blocks which step in long-chain fatty acid oxidation?
58. A patient has markedly elevated serum triglycerides with xanthomas, lipaemia retinalis, and recurrent pancreatitis. Genetic testing confirms homozygous lipoprotein lipase (LPL) deficiency (Fredrickson type I). The primary biochemical defect causing chylomicron accumulation is:
59. Familial hypercholesterolemia (FH) is caused by loss-of-function mutations in the LDL receptor (LDLR). In FH, statins have reduced efficacy compared to normal individuals because:
60. In peroxisomal beta-oxidation, which structural class of fatty acids is EXCLUSIVELY oxidized in peroxisomes and cannot be handled by mitochondrial beta-oxidation?
61. A patient with familial hypercholesterolaemia (FH) has markedly elevated LDL despite high-dose statin therapy. Genetic testing reveals homozygous gain-of-function mutation in PCSK9. The mechanism by which this PCSK9 mutation elevates LDL is:
62. A patient with Type V hyperlipoproteinaemia (familial hypertriglyceridaemia) presents with acute pancreatitis and eruptive xanthomata. Serum shows turbid plasma with both elevated chylomicrons and VLDL. The enzyme whose activity is PRIMARILY deficient in Type V hyperlipoproteinaemia is:
63. Reverse cholesterol transport (RCT) is the process by which peripheral cell cholesterol is returned to the liver. The FIRST step of RCT involving HDL formation from lipid-poor apoA-I and membrane phospholipids requires:
64. Familial hypercholesterolaemia (FH) is most commonly caused by loss-of-function mutations in LDL receptor (LDLR). However, some patients have autosomal dominant hypercholesterolaemia without LDLR mutation. The second most common genetic cause involves gain-of-function mutations in:
65. Abetalipoproteinaemia is a rare autosomal recessive disorder characterised by fat malabsorption, acanthocytosis, ataxia, and retinitis pigmentosa. The biochemical defect is:
66. Familial hypercholesterolemia (FH) is caused by LDL receptor mutations. In compound heterozygous FH with two different LDL receptor mutations, a Western blot of patient fibroblasts shows LDL receptors of normal size but their surface expression is severely reduced. The mutation MOST likely affects:
67. Lipoprotein lipase (LPL) deficiency causes hyperchylomicronemia. A patient presents with pancreatitis, eruptive xanthomas, lipemia retinalis, and triglycerides >2000 mg/dL. The role of LPL in normal triglyceride clearance is:
68. Statins inhibit HMG-CoA reductase. Beyond reducing LDL-cholesterol synthesis, statins upregulate LDL receptors. The MOLECULAR mechanism by which statin-induced mevalonate depletion increases LDL receptor expression is:
69. Abetalipoproteinaemia presents with fat malabsorption, retinitis pigmentosa, ataxia, and acanthocytosis. The defect is in the MTP (microsomal triglyceride transfer protein) gene, preventing assembly of which lipoprotein?
70. In fatty acid beta-oxidation, the entry of long-chain fatty acyl-CoA into the mitochondria requires carnitine shuttle. Which enzyme on the inner mitochondrial membrane regenerates free carnitine inside the mitochondrial matrix?
71. Familial hypercholesterolaemia (FH) is most commonly caused by mutations in the LDL receptor gene. How does LDL receptor deficiency cause elevated circulating LDL?
72. A patient with familial hypercholesterolaemia (FH) has a defective LDL receptor. LDL particles are not cleared, leading to hypercholesterolaemia. PCSK9 inhibitors lower LDL by:
73. Malonyl-CoA inhibits CPT-I (carnitine palmitoyltransferase I), serving as a key regulatory link between fatty acid synthesis and oxidation. Malonyl-CoA levels are HIGH in the:
74. Lipoprotein lipase (LPL) deficiency causes type I hyperlipoproteinaemia characterised by a markedly elevated fasting plasma triglyceride. The creamy supernatant on standing of such plasma indicates excess:
75. A 35-year-old man presents with eruptive xanthomas over the buttocks and back, severe abdominal pain, and serum triglycerides of 4800 mg/dL. Plasma turbidity clears at 4°C (cream layer forms at the top). Lipoprotein electrophoresis shows a prominent chylomicron band. Deficiency of which enzyme or protein is the most likely cause?
76. In hepatic fatty acid oxidation, the enzyme enoyl-CoA hydratase acts on trans-2-enoyl-CoA to produce a specific stereoisomer of 3-hydroxyacyl-CoA. Which stereoisomeric form is produced, and why is this specificity important?
77. A student reads that ketone bodies serve as an important fuel for the brain during prolonged starvation. Which of the following correctly describes the rate-limiting step in ketogenesis in the liver?
78. A 50-year-old woman with hypothyroidism is found to have elevated LDL cholesterol. Thyroid hormone normally upregulates hepatic LDL receptor expression. In her hypothyroid state, LDL clearance is reduced. Which intracellular mechanism, when LDL enters a cell via its receptor, normally prevents cholesterol overload?
79. Carnitine palmitoyl transferase I (CPT-I) is the rate-limiting enzyme for long-chain fatty acid entry into mitochondria for beta-oxidation. In the fed state, which metabolite specifically inhibits CPT-I, thereby preventing futile cycling between fatty acid synthesis and oxidation?