8.2 Fatty acid breakdown
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88 Terms
What is fat metabolism primarily concerned with?
Storage, mobilisation, synthesis, and oxidation of lipids for energy.
What is the major fuel storage form in humans?
Triacylglycerol (TAG).
Why is triacylglycerol an efficient energy store?
Highly reduced, anhydrous, and energy dense.
How much TAG does a typical 70 kg non-obese person store?
Approximately 11 kg.
Where is TAG mainly stored?
Adipose tissue.
What is triacylglycerol made of?
Glycerol esterified to three fatty acids.
What are saturated fatty acids?
Fatty acids with no double bonds.
What are monounsaturated fatty acids?
Fatty acids with one double bond.
What are polyunsaturated fatty acids?
Fatty acids with multiple double bonds.
What is the first step in fat mobilisation?
Triacylglycerol breakdown (lipolysis).
What enzyme breaks down triacylglycerol?
Hormone-sensitive lipase.
What are the products of TAG breakdown?
Fatty acids and glycerol.
What stimulates hormone-sensitive lipase?
Glucagon and adrenaline.
When is lipolysis stimulated?
Low blood glucose / fasting.
How does glucagon stimulate lipolysis?
Receptor → adenylate cyclase → cAMP → protein kinase A → hormone-sensitive lipase activation.
What second messenger mediates glucagon lipolysis signalling?
cAMP.
What activates hormone-sensitive lipase directly?
Protein kinase A phosphorylation.
What happens to glycerol released from TAG?
Used in glycolysis or gluconeogenesis.
What happens to released fatty acids?
Transported to tissues for oxidation.
Why can’t fatty acids circulate freely in plasma?
They are hydrophobic and insoluble in water.
How are fatty acids transported in blood?
Bound to albumin.
Which tissues commonly oxidise fatty acids?
Skeletal muscle and heart.
What is β-oxidation?
Mitochondrial breakdown of fatty acids to generate energy.
Where does β-oxidation occur?
Mitochondria.
Why is β-oxidation called β-oxidation?
Oxidation occurs at the β-carbon.
How many carbons are removed per β-oxidation cycle?
2 carbons.
In what form are 2 carbons removed?
Acetyl CoA.
What must happen before fatty acids enter mitochondria?
Activation to fatty acyl CoA.
What enzyme activates fatty acids?
Fatty acyl CoA synthetase.
What molecule is attached during activation?
Coenzyme A.
Can fatty acyl CoA cross the inner mitochondrial membrane directly?
No.
How are fatty acids transported into mitochondria?
Carnitine shuttle.
What enzyme forms acyl-carnitine?
Carnitine acyltransferase (CPT1).
What does CPT1 stand for?
Carnitine palmitoyl transferase 1.
What transporter moves acyl-carnitine across the inner membrane?
Carnitine-acylcarnitine translocase.
What happens once acyl-carnitine enters mitochondria?
Converted back to fatty acyl CoA.
Why is the carnitine shuttle necessary?
Inner mitochondrial membrane is impermeable to fatty acyl CoA.
What are the four steps of β-oxidation?
Oxidation, hydration, oxidation, thiolysis.
First β-oxidation step?
FAD-dependent oxidation.
Product of first oxidation?
Enoyl CoA.
What cofactor is reduced in first oxidation?
FAD → FADH₂.
Second β-oxidation step?
Hydration.
Product after hydration?
L-hydroxyacyl CoA.
Third β-oxidation step?
NAD+-dependent oxidation.
Product after second oxidation?
Ketoacyl CoA.
What cofactor is reduced in second oxidation?
NAD+ → NADH.
Final β-oxidation step?
Thiolysis.
What happens in thiolysis?
Acetyl CoA removed, chain shortened by 2 carbons.
Products of one β-oxidation cycle?
1 acetyl CoA, 1 NADH, 1 FADH₂, shortened fatty acyl CoA.
What happens to acetyl CoA from β-oxidation?
Enters citric acid cycle or ketogenesis.
Why is β-oxidation energy rich?
Produces reduced cofactors and acetyl CoA.
Complete oxidation of palmitoyl CoA yields approximately how much ATP?
~129 ATP (lecture value).
Why does fatty acid oxidation yield more ATP than glucose?
Fatty acids are more reduced.
What percentage of stored energy is captured?
Approximately 40%.
What happens to odd-chain fatty acids?
Produce acetyl CoA plus propionyl CoA.
What happens to propionyl CoA?
Converted to succinyl CoA.
Why is succinyl CoA important?
Enters the citric acid cycle.
How are unsaturated fatty acids oxidised?
Double bonds are repositioned and reduced if needed.
What cofactor may be required for unsaturated FA oxidation?
NADPH.
What controls β-oxidation rate?
Fatty acid availability and carnitine shuttle entry.
How does lipolysis affect β-oxidation?
More fatty acid supply increases oxidation.
What inhibits β-oxidation?
Malonyl CoA.
Why does malonyl CoA inhibit β-oxidation?
Prevents simultaneous synthesis and breakdown.
How does malonyl CoA inhibit β-oxidation?
Inhibits CPT1/acyl-carnitine formation.
What does high malonyl CoA indicate?
Fed state / fatty acid synthesis active.
What are ketone bodies?
Water-soluble fuel molecules made from excess acetyl CoA.
Main ketone bodies?
Acetoacetate, 3-hydroxybutyrate, acetone.
Where are ketone bodies synthesised?
Liver.
When is ketogenesis increased?
Starvation, diabetes, prolonged fasting.
Why does ketogenesis occur?
Acetyl CoA accumulates when oxaloacetate is limited.
Why is oxaloacetate low during starvation?
Used for gluconeogenesis.
Why can’t excess acetyl CoA enter the citric acid cycle in starvation?
Insufficient oxaloacetate.
What tissues use ketone bodies?
Heart, kidney cortex, brain during starvation.
Why can’t the brain normally use fatty acids?
Blood-brain barrier restricts entry.
Why are ketone bodies useful for the brain?
They are water soluble and cross into brain tissue.
What happens to adipose tissue during starvation?
Releases fatty acids.
What does liver do with starvation fatty acids?
Oxidises them and produces ketone bodies.
Why can excessive ketone body production be dangerous?
Causes ketoacidosis.
What is ketoacidosis?
Acidification of blood due to excess ketone bodies.
Can humans convert fatty acids into glucose?
No.
Why can’t humans convert fatty acids into glucose?
Acetyl CoA cannot be converted back to pyruvate.
Why is acetyl CoA conversion impossible in humans?
Pyruvate dehydrogenase is irreversible.
What is the glyoxylate cycle?
A pathway allowing conversion of acetyl CoA to glucose.
Which organisms use the glyoxylate cycle?
Plants and bacteria.
Why can plants convert fat to glucose?
They possess the glyoxylate cycle.
Where does the glyoxylate cycle occur in plants?
Glyoxysomes.
Why is the glyoxylate cycle important in seedlings?
Provides glucose before photosynthesis begins.
Overall function of fatty acid breakdown?
Generate ATP during fasting and energy demand.