Lipid Chemistry (Sphingolipids, Eicosanoids, Ketogenesis) MCQs

Biochemistry · 31 free questions with answers & explanations.

1. A 6-month-old infant presents with progressive neurological deterioration, hypotonia, cherry-red spot on fundoscopy, and hepatosplenomegaly. Enzyme assay confirms hexosaminidase A and B deficiency. This is consistent with:
2. A 6-month-old infant presents with progressive neurological deterioration, loss of previously acquired skills, a cherry-red spot on fundoscopy, and hepatosplenomegaly. Bone marrow biopsy shows 'foam cells.' Enzyme assay reveals absent hexosaminidase A AND B activity. This presentation is MOST consistent with:
3. A 6-month-old infant has progressive neurological deterioration with macrocephaly, a cherry-red spot on macula, exaggerated startle response, and hypotonia. Hexosaminidase A activity is absent. Which sphingolipid accumulates, and in which organelle?
4. Ketone body synthesis (ketogenesis) occurs exclusively in hepatic mitochondria. The rate-limiting regulated enzyme in ketogenesis that is NOT a simple condensation but an irreversible committed step is:
5. Gaucher disease type 1 (non-neuronopathic) results from glucocerebrosidase (acid beta-glucosidase) deficiency with accumulation of glucocerebroside in macrophages/Kupffer cells. Enzyme replacement therapy (imiglucerase, velaglucerase) is available. Substrate reduction therapy with eliglustat inhibits which enzyme?
6. In diabetic ketoacidosis (DKA), ketogenesis is activated due to high glucagon:insulin ratio. Acetyl-CoA derived from unchecked beta-oxidation is channeled into ketone body synthesis in hepatic mitochondria. The committed step in ketogenesis is catalyzed by HMG-CoA synthase (mitochondrial). Why is ketogenesis limited to the LIVER (and not muscle or adipose tissue) despite these tissues also performing beta-oxidation?
7. Thromboxane A2 (TXA2) and prostacyclin (PGI2) are derived from prostaglandin H2 (PGH2) via opposing enzymes — thromboxane synthase (in platelets) and prostacyclin synthase (in vascular endothelium), respectively. Low-dose aspirin selectively inhibits platelet COX-1 irreversibly. Platelets lack nuclei and cannot re-synthesize COX-1. Endothelial cells recover COX activity within hours by new protein synthesis. This forms the pharmacological basis for cardioprotection. Why is it important that aspirin's effect on platelet TXA2 is NOT offset by equal suppression of endothelial PGI2 at low doses?
8. Niemann-Pick disease type A is caused by acid sphingomyelinase deficiency, leading to sphingomyelin accumulation in lysosomes. Sphingomyelin is structurally unique among membrane phospholipids because:
9. Tay-Sachs disease is caused by deficiency of hexosaminidase A (HexA, alpha subunit), while Sandhoff disease is caused by deficiency of both hexosaminidase A and B (beta subunit). Both diseases accumulate GM2 ganglioside. A cherry-red spot at the macula and progressive neurodegeneration are characteristic. How is Tay-Sachs disease distinguished from Sandhoff disease biochemically?
10. In prolonged starvation, the liver produces ketone bodies that serve as alternative fuel for the brain. The rate-limiting regulated enzyme for ketogenesis is:
11. Niemann-Pick disease type C (NPC) differs from types A and B. While NPC-A and B result from sphingomyelinase deficiency, NPC-C is caused by a defect in cholesterol trafficking. Which protein is defective in NPC-C and what is its normal function?
12. Aspirin irreversibly inhibits cyclooxygenase (COX) by acetylating serine 529 of COX-1 and serine 516 of COX-2. In platelets, this is therapeutically beneficial for preventing thrombosis. Why does aspirin inhibit thromboxane A2 (TXA2) production more selectively than prostacyclin (PGI2) synthesis at low doses?
13. A 6-month-old infant with cherry-red spot on fundoscopy, progressive neurodegeneration, and foam cells in the bone marrow has absent hexosaminidase A (Hex A) activity. Hex A is composed of α and β subunits. Which specific subunit mutation causes Tay-Sachs, and what accumulates in neurons?
14. Gaucher disease type 1 is the most common lysosomal storage disorder, caused by glucocerebrosidase (GBA) deficiency. Imiglucerase (recombinant glucocerebrosidase) is used for enzyme replacement therapy (ERT). What modification of recombinant glucocerebrosidase is essential for its targeting to macrophage lysosomes?
15. During prolonged fasting, hepatic ketogenesis increases. The key committed step in ketogenesis is catalysed by HMG-CoA synthase 2 (mitochondrial). Which mechanism prevents ketone body utilisation by the liver itself?
16. Gaucher disease (glucocerebrosidase deficiency) type 1 (non-neuronopathic) is the most common lysosomal storage disorder among Ashkenazi Jews. The substrate that accumulates is glucocerebroside (glucosylceramide). Which cell type predominantly accumulates this lipid, and what is the characteristic histological finding?
17. In eicosanoid biosynthesis, 5-lipoxygenase (5-LOX) converts arachidonic acid to which intermediate before producing leukotrienes?
18. HMG-CoA lyase deficiency presents with hypoketotic hypoglycemia during fasting, similar to MCAD deficiency but differs because it also causes metabolic acidosis with elevated 3-hydroxy-3-methylglutaric acid. HMG-CoA lyase catalyses which reaction?
19. A patient presents with progressive ataxia, cherry-red spot on macula, splenomegaly, and foam cells on bone marrow biopsy. Glucocerebrosidase (acid beta-glucosidase) activity is markedly reduced. The lipid that accumulates in Gaucher's disease and the sphingoid base backbone of this glycosphingolipid are:
20. Thromboxane A2 (TXA2) and prostacyclin (PGI2) are both derived from arachidonic acid via the cyclooxygenase pathway. They have opposing effects on platelet aggregation and vascular tone. The enzyme that synthesises TXA2 in platelets and the receptor through which it promotes aggregation are:
21. Gaucher disease involves accumulation of glucocerebrosides in macrophages of the spleen, liver, and bone marrow. The enzyme deficient in Gaucher disease is:
22. HMG-CoA in the mitochondria is a branch point metabolite. In which two metabolic pathways does it serve as an intermediate, and which enzyme commits it to ketogenesis?
23. A patient with Gaucher disease has a bone marrow biopsy showing 'crinkled paper' macrophages. The deficient lysosomal enzyme and its substrate are:
24. Gaucher disease (glucocerebrosidase deficiency) causes accumulation of glucocerebroside in macrophages of liver, spleen, and bone marrow. The 'Gaucher cell' is a macrophage with a characteristic appearance described as:
25. A 6-month-old infant with progressive neurodegeneration, cherry-red spot, and hepatosplenomegaly has foamy macrophages on bone marrow biopsy. Enzyme assay reveals absent beta-glucocerebrosidase. This enzyme cleaves which bond in glucocerebroside?
26. Thromboxane A2 (TXA2) and prostacyclin (PGI2) have opposing effects on platelet aggregation and vascular tone. Which statement correctly describes the mechanism of this physiological antagonism?
27. Gaucher disease (type I) presents with hepatosplenomegaly, pancytopenia from bone marrow infiltration, and Erlenmeyer flask deformity. Enzyme replacement therapy uses recombinant glucocerebrosidase. The substrate that accumulates is glucocerebroside, which is enriched in which specific cell type?
28. Niemann-Pick disease type C (NPC) is caused by mutations in NPC1 or NPC2 proteins involved in intracellular cholesterol trafficking. The biochemical defect in NPC is FUNDAMENTALLY different from NPC type A/B because:
29. Gaucher disease is the most common lysosomal storage disorder. Glucocerebrosidase (glucosylceramidase) deficiency leads to glucocerebroside accumulation in macrophages. Which cell feature is pathognomonic on bone marrow biopsy?
30. Niemann-Pick disease type A is caused by sphingomyelinase deficiency, leading to sphingomyelin accumulation. The cell type primarily engorged with lipid is:
31. Thromboxane A2 (TXA2) and prostacyclin (PGI2) have opposing effects on platelet aggregation. The enzyme that produces TXA2 in platelets and is inhibited by low-dose aspirin is: