Chapter 22: Lipid Metabolism

Question 1

Use of TAGs for fuel

Answer 1

The fatty acids incorporated into triacylglycerols in adipose tissue are made accessible in three stages:

1. Degradation of TAGs to release fatty acids and glycerol into the blood for transport to energy-requiring tissues
2. Activation of the fatty acids and transport into the mitochondria for oxidation
3. Oxidation of the fatty acids to acetyl CoA for processing by the CAC

Produces one FADH₂, one NADH, and one fatty acetyl CoA per cycle

Question 2

Hormonal regulation of lipolysis

Answer 2

Stimulated by:

• Glucagon
• Epinepherine
• Cortisol

Inhibited by:

• Insulin

Question 3

Glycerol degradation

Answer 3

Question 4

Fatty acid activation

Answer 4

Begins with an activation step in the cytosol (FA-1) that requires the energy of ATP hydrolysis

• FA-1⇢ catalyzed by acyl CoA synthetase; drives the attachment of a CoA molecule to the fatty acid forming fatty acetyl CoA

The fatty acetyl CoA is then transported into the mitochondrion by a translocase in the inner membrane

Question 5

Movement of fatty acetyl CoA into the mitochondria

Answer 5

Carnitine carries long-chain activated fatty acids into the mitochondiral matrix

Carnitine acyltransferase 1 is located in the outer mitochondiral membrane

• Replaces the CoA group with a carnitine group to move the fatty acid across the membrane

Carnitine acyltransferase 2 is located in the inner mitochondiral membrane

• Removes the carnitine group and reattaches the CoA, regenerating the fatty acetyl CoA

Question 6

Degradation of fatty acetyl CoA

Answer 6

FA-2⇢ An integral membrane dehydrogenase oxidizes the fatty acetyl CoA, forming a double bond between the α and β-carbons

• The two electrons and protons removed are transferred to FAD, forming one FADH₂

FA-3⇢ water is added across the double bond by a hydratase

FA-4⇢ another dehydrogenase re-oxidizes the β-carbon, forming a ketone

• The two electrons and protons removed are transferred to NAD⁺, forming one NADH

FA-5⇢ the bond between the α and ß-carbons is broken by a thiolase and a two-carbon fragment is transferred to a second acetyl CoA

The steps FA-2 to FA-5 are repeated until the original fatty acid is completely degraded

Question 7

Enzymes required to metabolize unsaturated fatty acids

Answer 7

Isomerase- gets it into right shape

Reductase- corrects the molecular geometry

Question 8

Degredation of odd-chain fatty acids

Answer 8

Propionyl CoA carboxylase adds a carbon to propionyl CoA to form methylmalonyl CoA

Methylmalonyl CoA mutase a vitamin B12-requiring enzyme, subsequently forms succinyl CoA from methylmalonyl CoA

Question 9

Driver of ketone body formation

Answer 9

Acetyl CoA formed via β-oxidation enters the CAC only if fat and carb degredation are balanced

In fasting or diabetes oxaloacetate is used to form glucose in the gluconeogenic pathway

In these situations acetyl CoA is diverted to form acetoacetate and D-3-hydroxybutyrate

These two molecules as well as acetone are often referred to as ketone bodies

Question 10

Ketone bodies

Answer 10

1. Acetoacetate
2. Acetone
3. D-3-hydroxybutyrate

Acetoacetate undergoes a slow, spontaneous decarboxylation to acetone

Question 11

Ketone bodies as fuel

Answer 11

Liver exports water-soluble ketones through the blood to other systems for use as fuel

Once ketones show up at their destination, they enter the CAC to be used as fuel