Glycerophospholipids

Flashcard 1 Q: Draw and label the general structure of a glycerophospholipid. What are the key components?

A: Structure: Glycerol backbone (3 carbons) → sn-1 and sn-2 positions esterified to fatty acyl chains; sn-3 position has a phosphate group linked via a phosphodiester bond to a polar head group (X). Components: Glycerol backbone, fatty acyl chains (sn-1, sn-2), phosphate group, polar head group (X).

Flashcard 2 Q: Which positions on the glycerol backbone are esterified to fatty acids, and which contain a phosphodiester bond?

A: The sn-1 and sn-2 positions are esterified to fatty acids (via ester bonds). The sn-3 position contains a phosphate group linked to the glycerol via a phosphodiester bond to the polar head group (X).

Flashcard 3 Q: Name the six major classes of glycerophospholipids based on their polar head group.

A: 1) Phosphatidylcholine (lecithin)

Phosphatidylethanolamine (cephalin)

Phosphatidylserine

Phosphatidylinositol

Phosphatidylglycerol

Cardiolipin (diphosphatidylglycerol)

Flashcard 4 Q: What is the polar head group of phosphatidylcholine, and what is its common name?

A: Polar head group: Choline. Common name: Lecithin.

Flashcard 5 Q: What is the polar head group of phosphatidylethanolamine, and what is its common name?

A: Polar head group: Ethanolamine. Common name: Cephalin.

Flashcard 6 Q: What are the polar head groups of phosphatidylserine, phosphatidylinositol, and phosphatidylglycerol?

A: Phosphatidylserine – Serine. Phosphatidylinositol – Inositol. Phosphatidylglycerol – Glycerol.

Flashcard 7 Q: What is cardiolipin, and where is it predominantly found?

A: Cardiolipin (diphosphatidylglycerol) consists of two phosphatidic acid molecules linked by a glycerol head group. It is predominantly found in the inner mitochondrial membrane and is essential for mitochondrial function.

Flashcard 8 Q: Write the activation reaction of fatty acids to acyl-CoA, including the enzyme, coenzyme, and energy cost.

A: Fatty acid + CoA-SH + ATP → Acyl-CoA + AMP + PPi. Enzyme: Acyl-CoA synthetase (fatty acid thiokinase). Coenzyme: CoA-SH. Energy cost: 2 high-energy bonds (ATP → AMP + PPi; PPi → 2 Pi).

Flashcard 9 Q: Write the reaction for the synthesis of phosphatidic acid from glycerol-3-phosphate.

A: Glycerol-3-phosphate + 2 Acyl-CoA → Phosphatidic acid + 2 CoA-SH. Enzymes: Step 1: Glycerol-3-phosphate acyltransferase (adds first acyl-CoA at sn-1). Step 2: 1-Acylglycerol-3-phosphate acyltransferase (adds second acyl-CoA at sn-2).

Flashcard 10 Q: What is phosphatidic acid, and why is it a central intermediate in glycerophospholipid synthesis?

A: Phosphatidic acid is a key intermediate that can be:

Dephosphorylated to diacylglycerol (DAG) for synthesis of phosphatidylcholine and phosphatidylethanolamine.

Activated to CDP-diacylglycerol for synthesis of phosphatidylinositol, phosphatidylglycerol, and cardiolipin.

Flashcard 11 Q: Write the reaction for the formation of CDP-diacylglycerol from phosphatidic acid.

A: Phosphatidic acid + CTP → CDP-diacylglycerol + PPi. Enzyme: CDP-diacylglycerol synthase. This is the activated form used in the CDP-diacylglycerol pathway.

Flashcard 12 Q: Which glycerophospholipids are synthesized via the CDP-diacylglycerol pathway?

A: Phosphatidylinositol, phosphatidylglycerol, and cardiolipin.

Flashcard 13 Q: Describe the activation of choline for the CDP-choline pathway.

A: Choline + ATP → Phosphocholine + ADP (enzyme: Choline kinase). Phosphocholine + CTP → CDP-choline + PPi (enzyme: CTP:phosphocholine cytidylyltransferase – rate-limiting enzyme).

Flashcard 14 Q: What is the rate-limiting enzyme in the CDP-choline pathway?

A: CTP:phosphocholine cytidylyltransferase. It is the key regulatory step for phosphatidylcholine synthesis.

Flashcard 15 Q: Write the final reaction for the synthesis of phosphatidylcholine via the CDP-choline pathway.

A: CDP-choline + Diacylglycerol (DAG) → Phosphatidylcholine + CMP. Enzyme: Choline phosphotransferase.

Flashcard 16 Q: How is phosphatidylethanolamine synthesized, and what enzyme catalyzes the final step?

A: Ethanolamine + ATP → Phosphoethanolamine + ADP (ethanolamine kinase). Phosphoethanolamine + CTP → CDP-ethanolamine + PPi (CTP:phosphoethanolamine cytidylyltransferase). CDP-ethanolamine + DAG → Phosphatidylethanolamine + CMP (Ethanolamine phosphotransferase).

Flashcard 17 Q: What is the structural role of glycerophospholipids in biological membranes?

A: Glycerophospholipids are the major structural components of membranes. They form a lipid bilayer with hydrophobic fatty acyl tails facing inward and hydrophilic head groups facing outward, providing a permeability barrier and matrix for membrane proteins.

Flashcard 18 Q: How does phosphatidylinositol (PI) function as a precursor for signaling molecules?

A: Phosphatidylinositol is sequentially phosphorylated to PIP₂ (phosphatidylinositol 4,5-bisphosphate). Upon receptor activation, phospholipase C (PLC) cleaves PIP₂ into IP₃ (inositol 1,4,5-trisphosphate) and DAG (diacylglycerol), both of which act as second messengers. IP₃ releases Ca²⁺ from the ER; DAG activates protein kinase C (PKC).

Flashcard 19 Q: What is the role of phospholipase A₂ (PLA₂) in glycerophospholipid signaling?

A: PLA₂ cleaves the fatty acid at the sn-2 position of glycerophospholipids, releasing arachidonic acid (a 20:4 fatty acid). Arachidonic acid is the precursor for eicosanoids (prostaglandins, leukotrienes, thromboxanes) – key inflammatory and signaling mediators.

Flashcard 20 Q: What is platelet-activating factor (PAF), and how is it derived from glycerophospholipids?

A: PAF is a potent signaling phospholipid. It is derived from phosphatidylcholine by PLA₂ (removing the sn-2 fatty acid, usually arachidonate) followed by acetylation at the sn-2 position with a short acetyl group. PAF mediates platelet aggregation, inflammation, and anaphylaxis.

Flashcard 21 Q: Where does the biosynthesis of glycerophospholipids primarily occur?

A: Glycerophospholipid biosynthesis primarily occurs in the endoplasmic reticulum (ER) of most cells. Cardiolipin synthesis occurs in the inner mitochondrial membrane.

Flashcard 22 Q: What is the source of the glycerol-3-phosphate used for glycerophospholipid synthesis?

A: Glycerol-3-phosphate is derived from:

Reduction of DHAP (from glycolysis) – in most tissues.

Phosphorylation of glycerol by glycerol kinase – in liver and kidney (not adipose tissue).

Flashcard 23 Q: What is the role of phosphatidylserine in the cell, and where is it predominantly located?

A: Phosphatidylserine (PS) is a negatively charged phospholipid. It is predominantly located in the inner leaflet of the plasma membrane. It plays a role in apoptosis (externalized PS is an "eat-me" signal for macrophages) and is a precursor for phosphatidylethanolamine (via decarboxylation).

Flashcard 24 Q: What is the role of cardiolipin in mitochondrial function?

A: Cardiolipin is essential for the structural integrity of the inner mitochondrial membrane. It binds to and stabilizes respiratory chain complexes (electron transport chain) and is required for optimal activity of ATP synthase and mitochondrial transporters.

Flashcard 25 Q: How are phosphatidylcholine and phosphatidylethanolamine synthesized in the liver?

A: They are primarily synthesized via the CDP-choline/CDP-ethanolamine pathways. Additionally, phosphatidylethanolamine can be converted to phosphatidylcholine by three successive methylation reactions (using S-adenosylmethionine as methyl donor) – this is important in the liver.

Flashcard 26 Q: What is the significance of the sn-1 vs. sn-2 fatty acyl composition of glycerophospholipids?

A: The sn-1 position typically contains a saturated fatty acid (e.g., palmitic, stearic). The sn-2 position typically contains an unsaturated fatty acid (e.g., oleic, linoleic, arachidonic). This asymmetry is crucial for membrane fluidity and for the release of signaling lipids (e.g., arachidonic acid from sn-2 by PLA₂).

Flashcard 27 Q: What is the role of phosphatidylinositol 4,5-bisphosphate (PIP₂) in cell signaling?

A: PIP₂ is a membrane phospholipid that serves as a precursor for second messengers. Upon activation of G-protein-coupled receptors or receptor tyrosine kinases, phospholipase C (PLC) cleaves PIP₂ into:

IP₃ – releases Ca²⁺ from intracellular stores.

DAG – activates protein kinase C (PKC).

Flashcard 28 Q: What enzyme synthesizes CDP-diacylglycerol, and why is this a key step?

A: CDP-diacylglycerol synthase catalyzes: Phosphatidic acid + CTP → CDP-diacylglycerol + PPi. This is a key step because CDP-diacylglycerol is the activated precursor for the synthesis of phosphatidylinositol, phosphatidylglycerol, and cardiolipin.

Flashcard 29 Q: What are the two main pathways for glycerophospholipid biosynthesis, and which lipids does each produce?

A: 1) CDP-diacylglycerol pathway → produces phosphatidylinositol, phosphatidylglycerol, and cardiolipin.

CDP-choline/CDP-ethanolamine pathway → produces phosphatidylcholine (lecithin) and phosphatidylethanolamine (cephalin).

Flashcard 30 Q: What is the clinical significance of phospholipase A₂ (PLA₂) and arachidonic acid release?

A: PLA₂ releases arachidonic acid from membrane phospholipids, which is then metabolized by cyclooxygenase (COX) to prostaglandins and thromboxanes, and by lipoxygenase (LOX) to leukotrienes. These eicosanoids are involved in inflammation, pain, fever, platelet aggregation, and bronchoconstriction. This is the target of anti-inflammatory drugs like aspirin and NSAIDs (which inhibit COX