Lipid metabolism – V: Phospholipid and Sphingolipid Metabolism

Question 1

What are the three main roles of phospholipids in cells?

Answer 1

Major components of cell membranes.

Source of arachidonic acid for eicosanoid biosynthesis.

Provide secondary messengers (e.g., DAG, IP3) during signal transduction.

Question 2

Which phospholipid-derived molecules act as secondary messengers in the Phospholipase C pathway?

Answer 2

Diacylglycerol (DAG) and Inositol triphosphate (IP3).

Question 2

What enzyme cleaves PIP2 into DAG and IP3?

Answer 2

: Phospholipase C.

Question 3

Name the enzyme responsible for adding the second acyl group to lysophosphatidic acid during phosphatidic acid synthesis.

Answer 3

Acyltransferase II.

Question 3

What structural components make up sphingolipids?

Answer 3

Sphingosine (or derivative).

A long-chain fatty acid.

A polar head group.

Question 4

How are sphingomyelins structurally distinct from other sphingolipids?

Answer 4

They contain phosphocholine or phosphoethanolamine as their polar head group

Question 5

Which sphingolipid is a major component of the myelin sheath?

Answer 5

Sphingomyelins.

Question 6

What distinguishes gangliosides from cerebrosides and globosides?

Answer 6

Gangliosides have sialic acid residues, giving them a negative charge at pH 7.

Question 7

What is the head group in a glucosylcerebroside?

Answer 7

Glucose.

Question 8

Which sphingolipids determine blood group antigens?

Answer 8

Glycosphingolipids (e.g., A and B antigens depend on specific sugar residues like GalNAc or Gal).

Question 9

Name the three sub-classes of sphingolipids.

Answer 9

Sphingomyelins.

Neutral glycolipids (e.g., cerebrosides, globosides).

Gangliosides.

Question 10

Which carbons in sphingosine are analogous to glycerol in phospholipids?

Answer 10

C-1, C-2, and C-3 of sphingosine.

Question 10

What enzyme synthesizes CDP-diacylglycerol during phosphatidic acid metabolism?

Answer 10

CDP-DAG synthase.

Question 10

What is the primary function of DAG in signaling pathways?

Answer 10

Activates Protein Kinase C, which phosphorylates target proteins

Question 11

What type of bond links the polar head group to ceramide in sphingomyelin?

Answer 11

Phosphodiester bond (to phosphocholine).

Question 12

Which glycolipid class contains complex oligosaccharides with sialic acid?

Answer 12

Gangliosides (e.g., GM2).

Question 13

What is the role of PIP2 in cellular signaling?

Answer 13

serves as a substrate for Phospholipase C to produce DAG and IP3.

Question 14

Why are phospholipids critical for β-oxidation?

Answer 14

They provide fatty acids for the process.

Question 15

Name a neutral glycolipid found in neural tissue plasma membranes.

Answer 15

Galactocerebroside.

Question 16

What enzyme converts phosphatidic acid to triacylglycerol?

Answer 16

Acyl-CoA:diacylglycerol acyltransferase (DGAT).

Question 17

What phospholipid-derived secondary messengers trigger calcium release and PKC activation?

Answer 17

IP3 (releases Ca²⁺ from ER) and DAG (activates Protein Kinase C).
Clinical Link: Targeted in hypertension drugs (e.g., PLC inhibitors).

Question 17

Which phospholipid is the primary source of arachidonic acid for inflammatory eicosanoids (e.g., prostaglandins)?

Answer 17

Phospholipids (via phospholipase A2 action).
Exam Tip: Arachidonic acid is a precursor for COX/LOX pathway products

Question 17

What distinguishes gangliosides from other glycosphingolipids?

Answer 17

Presence of sialic acid (confers negative charge at pH 7).
Clinical Relevance: GM1 gangliosidosis involves GM1 accumulation due to β-galactosidase deficiency.

Question 17

A patient presents with recurrent infections and neuropathy. Lab work shows abnormal myelin. Which sphingolipid is likely deficient?

Answer 17

Sphingomyelins (critical for myelin sheath integrity).
Disease Link: Hereditary sensory neuropathy type 1 (SPTLC1 mutations).

Question 18

Why are glycosphingolipids critical in blood group antigen determination?

Answer 18

Their sugar head groups (e.g., GalNAc for A antigen, Gal for B antigen) define ABO system. Easy-to-Miss: Found on red blood cell membranes.

Question 18

Which enzyme deficiency causes Tay-Sachs disease, and what sphingolipid accumulates?

Answer 18

Hexosaminidase A deficiency → GM2 ganglioside accumulation. Key Symptom: Cherry-red spot on macula.

Question 19

What is the clinical significance of elevated glucosylceramide?

Answer 19

Gaucher disease (due to glucocerebrosidase deficiency). Presentation: Hepatosplenomegaly, bone pain, "crumpled tissue paper" macrophages.

Question 20

Which carbons in sphingosine mirror glycerol in phospholipids, and why does this matter?

Answer 20

C-1, C-2, C-3 → Structural analogy explains similar membrane integration. High-Yield: Often tested in comparative lipid biochemistry.

Question 21

What role does cardiolipin (diphosphatidyl glycerol) play clinically?

Answer 21

Stabilizes mitochondrial membranes (electron transport chain). Disease Link: Barth syndrome (cardiolipin remodeling defects → cardiomyopathy).

Question 22

A patient has fat malabsorption. Which phospholipid-related process is impaired?

Answer 22

Micelle formation (requires phospholipids like phosphatidylcholine to solubilize fats). Key Enzyme: Pancreatic phospholipase A2.

Question 23

What enzyme converts phosphatidic acid to triacylglycerol, and where is it located?

Answer 23

DGAT (acyl-CoA:diacylglycerol acyltransferase) in the ER. Therapeutic Target: Obesity/diabetes drugs inhibit DGAT to reduce fat storage.

Question 24

Why are sphingomyelins classified as phospholipids despite being sphingolipids?

Answer 24

They contain a phosphocholine/phosphoethanolamine head group. Exam Trap: Sphingomyelins bridge both categories—don’t confuse with glycolipids!

Question 25

Which signaling molecule is both a phospholipid derivative and a precursor for platelet-activating factor (PAF)?

Answer 25

DAG (modified to form PAF, a potent inflammatory mediator). Clinical Link: PAF antagonists used in asthma/allergy.

Question 26

What structural feature makes cerebrosides neutral at pH 7?

Answer 26

Uncharged sugar head groups (e.g., glucose/galactose). Contrast: Gangliosides are acidic due to sialic acid.

Question 27

Which phospholipid is critical for lung surfactant function, and what happens if deficient?

Answer 27

Dipalmitoylphosphatidylcholine (DPPC) → Neonatal respiratory distress syndrome (NRDS). Treatment: Synthetic surfactant (e.g., beractant).

Question 28

How does Phospholipase C contribute to hormone signaling (e.g., vasopressin)?

Answer 28

Cleaves PIP2 → IP3 (↑ intracellular Ca²⁺) + DAG (activates PKC). High-Yield Pathway: IP3/DAG system is ubiquitous in cell signaling exams.

Question 29

What distinguishes globosides from cerebrosides?

Answer 29

Globosides have 2+ sugars (e.g., lactosylceramide); cerebrosides have one. Clinical Angle: Globoside accumulation in Fabry disease (α-galactosidase A deficiency).

Question 30

Why are phospholipids essential for β-oxidation?

Answer 30

They release fatty acids (via phospholipases) for mitochondrial energy production. Easy-to-Forget: Phospholipids aren’t just structural!

Question 31

Which sphingolipid lacks a phosphate group and is a pure glycolipid?

Answer 31

Cerebrosides (e.g., galactocerebroside in neural tissue). Contrast: Sphingomyelins have phosphocholine → technically phospholipids.