PHA 339 - Lecture #11 (Lipolysis)

Fatty acids definition

Fatty acids are long-chain hydrocarbon molecules with a terminal carboxyl group that can be used as a major source of energy.

Fatty acid synthesis overview

Fatty acid synthesis occurs in the cytosol and converts acetyl CoA into fatty acids using ATP and NADPH.

Key enzyme of fatty acid synthesis

The key regulatory enzyme of fatty acid synthesis is acetyl CoA carboxylase.

Steps of fatty acid synthesis

Step 1: Acetyl CoA is converted to malonyl CoA by acetyl CoA carboxylase. Step 2: Fatty acid synthase catalyzes the sequential addition of two-carbon units to form a growing fatty acid chain. Step 3: The fatty acid chain is elongated and eventually released as palmitate.

Acetyl CoA carboxylase reaction (Step 1)

______ converts acetyl CoA to malonyl CoA. This is the rate-limiting step of fatty acid synthesis.

Fatty acid synthase reaction (Step 2)

______ catalyzes the formation of a growing fatty acid chain by adding two-carbon units.

Fatty acid synthesis energy

Fatty acid synthesis requires ATP and NADPH.

Storage of fatty acids

Fatty acids are stored in the body as triacylglycerols (TAG) in adipose tissue.

Lipolysis definition

Lipolysis is the breakdown of stored triacylglycerols into free fatty acids and glycerol.

Fat mobilization definition

Fat mobilization refers to the release of free fatty acids from adipose tissue into the blood for use as energy.

Products of lipolysis

The products of lipolysis are free fatty acids (FFA) and glycerol.

Hormone-sensitive lipase reaction

______ hydrolyzes stored TAG into free fatty acids and glycerol in adipocytes.

Transport of fatty acids in blood

Free fatty acids are transported in the blood bound to serum albumin.

Fatty acid uptake

Fatty acids enter cells and are activated to fatty acyl CoA before metabolism.

Fatty acid activation

Fatty acids are converted to fatty acyl CoA by acyl CoA synthetase.

Transport into mitochondria

Fatty acyl CoA cannot directly enter the mitochondria and must be transported via the carnitine shuttle.

Carnitine shuttle overview

The carnitine shuttle transports fatty acyl groups into the mitochondria for β-oxidation.

Carnitine acyltransferase I reaction

______ transfers the fatty acyl group to carnitine to form acyl-carnitine.

Carnitine acyltransferase II reaction

______ transfers the fatty acyl group from carnitine back to CoA in the mitochondria.

Fatty acid β-oxidation definition

Fatty acid β-oxidation is the process of breaking down fatty acids into acetyl CoA units in the mitochondria.

Steps of β-oxidation

Step 1: Oxidation produces FADH2. Step 2: Hydration of the double bond. Step 3: Oxidation produces NADH. Step 4: Cleavage produces acetyl CoA.

β-oxidation oxidation step 1 (enzyme)

______ catalyzes the first oxidation step producing FADH2.

β-oxidation hydration step (enzyme)

______ catalyzes the hydration of the double bond.

β-oxidation oxidation step 2 (enzyme)

______ catalyzes the second oxidation step producing NADH.

β-oxidation cleavage step (enzyme)

______ catalyzes the cleavage to release acetyl CoA.

Products of β-oxidation

Each cycle of β-oxidation produces one FADH2, one NADH, and one acetyl CoA.

Energy yield of β-oxidation

Oxidation of fatty acids produces large amounts of ATP through the production of NADH and FADH2, which enter the electron transport chain, and acetyl CoA, which enters the TCA cycle.

Palmitate energy yield

Complete oxidation of palmitate yields 129 ATP.

Regulation of fatty acid metabolism

Fatty acid synthesis and β-oxidation are reciprocally regulated.

Malonyl CoA regulation

Malonyl CoA inhibits carnitine acyltransferase I, preventing fatty acid entry into mitochondria during synthesis.

Fed vs fasting (fatty acids)

Fed state: Fatty acid synthesis is increased. Fasting state: Lipolysis and β-oxidation are increased.

When lipolysis is stimulated

Fasting, exercise, low insulin, high glucagon or epinephrine

Location of fatty acid activation

Occurs on the outer mitochondrial membrane (cytosolic side)

Enzyme of fatty acid activation

Acyl-CoA synthetase (thiokinase)

Transport protein in carnitine shuttle

Carnitine-acylcarnitine translocase moves acyl-carnitine across inner mitochondrial membrane

Location of β-oxidation

Mitochondrial matrix

Final outcome of complete β-oxidation

Multiple acetyl-CoA molecules that enter the TCA cycle

Net ATP yield of palmitate oxidation

Approximately 106 ATP (after subtracting activation cost)

Why fatty acids require albumin transport

Long-chain fatty acids are hydrophobic and poorly soluble in plasma

Why glycerol is sent to liver

Adipocytes lack glycerol kinase

Purpose of fat mobilization

To provide energy to peripheral tissues during low glucose state