A researcher uses a drug that specifically blocks the phosphatase enzyme converting phosphatidic acid (PA) to diacylglycerol (DAG). Which prediction is MOST accurate about the effect on phospholipid synthesis?
AAll phospholipid synthesis halts immediately because DAG is required for all phospholipid classes
BSynthesis of phosphatidylcholine and phosphatidylethanolamine is impaired, but phosphatidylinositol and cardiolipin may continue via the CDP-diacylglycerol branch from PA
COnly the fatty acid composition of membrane phospholipids is affected; head group attachment continues normally
DCholesterol synthesis increases to compensate for the reduced phospholipid content in membranes
Phosphatidic acid (PA) is the branch point in the Kennedy pathway. It can either be dephosphorylated to DAG (leading to phosphatidylcholine and phosphatidylethanolamine) or converted to CDP-diacylglycerol (leading to phosphatidylserine, phosphatidylinositol, and cardiolipin). Blocking the PA→DAG step impairs the first branch but not the second. Option A is wrong because PA itself feeds the second branch directly.
Question 2 Multiple Choice
Why is CTP (cytidine triphosphate) required for phospholipid head group attachment in the Kennedy pathway?
ACTP directly phosphorylates the glycerol backbone to create phosphatidic acid from glycerol-3-phosphate
BCTP activates the head group (e.g., choline) by forming a high-energy CDP-choline intermediate, making the subsequent transfer to DAG thermodynamically favorable
CCTP removes the sn-2 fatty acid from phosphatidic acid during the Lands cycle remodeling step
DCTP is the primary carbon donor for extending fatty acid chains that are incorporated into the phospholipid backbone
The Kennedy pathway uses the same biochemical strategy as other biosynthetic pathways: activation by a nucleotide triphosphate drives an otherwise unfavorable condensation reaction. Choline is first phosphorylated (to phosphocholine), then activated with CTP to form CDP-choline — a high-energy intermediate. This activation makes the transfer of the choline head group to DAG thermodynamically favorable, releasing CMP. This is analogous to UTP activating glucose in glycogen synthesis.
Question 3 True / False
The Lands cycle allows cells to modify the fatty acid composition of membrane phospholipids after initial synthesis by exchanging the fatty acid at the sn-2 position.
TTrue
FFalse
Answer: True
The Lands cycle is a phospholipid remodeling system: phospholipase A₂ removes the fatty acid at the sn-2 position, and a lysophospholipid acyltransferase installs a different one. This post-synthetic remodeling is how cells generate the enormous diversity of phospholipid molecular species (hundreds of combinations of head groups, chain lengths, and saturation levels) from a relatively simple synthetic pathway, enabling precise tuning of membrane fluidity and curvature.
Question 4 True / False
Once a phospholipid is assembled via the Kennedy pathway, its fatty acid composition is permanently fixed and can seldom be changed without degrading and resynthesizing the entire molecule.
TTrue
FFalse
Answer: False
This is incorrect. The Lands cycle specifically provides a mechanism for remodeling phospholipid fatty acid composition without resynthesis. Phospholipase A₂ cleaves the sn-2 fatty acid, and acyltransferases install a replacement. This is how cells fine-tune membrane properties — adjusting fluidity, curvature, and signaling capacity — in response to changing needs. The Kennedy pathway synthesizes the structural scaffold; the Lands cycle customizes the content.
Question 5 Short Answer
What is the role of phosphatidic acid (PA) in the Kennedy pathway, and why is its position at the branch point important for understanding how cells produce diverse phospholipid classes?
Think about your answer, then reveal below.
Model answer: Phosphatidic acid is the common precursor formed after two fatty acid chains are attached to the glycerol-3-phosphate backbone. Its position at the branch point is critical because it is converted by two different enzymes into two different products: dephosphorylation yields diacylglycerol (DAG), which feeds synthesis of phosphatidylcholine and phosphatidylethanolamine; conversion by CTP yields CDP-diacylglycerol, which feeds synthesis of phosphatidylserine, phosphatidylinositol, and cardiolipin. This single branch point allows one common synthetic route to diverge into all major phospholipid classes, with the relative flux through each branch determining the membrane's lipid composition.
Understanding PA as a branch point explains how mutations or drugs affecting specific enzymes at or after this point selectively impair some phospholipid classes but not others — a conceptually important feature of membrane biochemistry that cannot be inferred from knowing the pathway as a linear sequence.