Week 9 Objectives

Question 1

Describe the processes by which fatty acids are transported in the blood, activated and transported into the matrix of the mitochondria for breakdown to obtain energy. (Specifically, determine the role of carnitine palmitoyl transferase in the oxidation of fatty acids.)

Answer 1

Beta Oxidation location: mitochondria matrix.

B-Oxidation is prepped by the Carnitine Shuttle pathway: Carnitine is taken through the IMM through CPTI then taken back by CPTII.

Malonyl-CoA inhibits CPTI to stop Beta Oxidation

• acetyl CoA makes malonyl CoA using Acetyl CoA carboxylase.
• ACC is activated by insulin, inhibited by glucagon/epinephrine

Question 2

Explain the processes by which fatty acids are released from triacylglycerol stored in adipose tissue.

Answer 2

Lipolysis= “hydrolysis of fat,” process of releasing free fatty acids from TAGs stored in the adipose in the FASTED state.

• HSL hydrolyzes TAGs into FFAs and glycerol
• inhibited by insulin
• activated by glucagon and epinephrine
• glycerol goes to liver, substrate for GNG

-Acetyl-CoA sythetase reconverts FFAs to acyl-CoA for resterification

Question 3

Outline the β-oxidation pathway by which fatty acids are metabolized to acetyl-CoA and explain how this leads to the production of large quantities of ATP.

Answer 3

-Purpose: Generate acetyl-CoA, FADH2, NADH
Start: Palmitoyl-CoA (acyl)
1. Dehydrogenation (acyl-CoA dehydrogenase w FADH2)
2. Hydration (enoyl-CoA hydratase)
3. Dehydrogenation (B-hydroxyacyl dehydrogenase w NADH)
4. Cleavage (thiolase)
End: Acyl-CoA and Acetyl-CoA
-NADH and FADH2 oxidized to make ATP

Question 4

Identify the three compounds termed “ketone bodies” and describe the reactions by which they are formed in liver mitochondria.

Answer 4

1. Acetoacetate
2. D-3hydroxybutyrate (B-hydroxybutyrate)

HMG CoA lyase cleaves HMG-CoA and produces acetoacate + acetyl-coA

Acetone can be reduced to D-3hydroxybutyrate or decarboxylated to acetone

Question 5

Recognize that ketone bodies are important fuels for extrahepatic tissues and indicate the conditions in which their synthesis and use are favored.

Answer 5

Ketogenesis occurs in the liver hepatocytes.

Skeletal muscle can oxidize ketones, brain can during starvation. Liver CANNOT

Question 6

Indicate the three stages in the metabolism of fatty acids where ketogenesis is regulated.

Answer 6

1. Activity of lipolysis
2. Cystolic levels of malonyl-coa (inhibits phosphate)
3. Flux thru the TCA cycle depending on NADH levels + concentration of intermediates (oxaloacetate)

Question 7

Indicate that overproduction of ketone bodies leads to ketosis and, if prolonged, ketoacidosis, and identify pathologic conditions when this occurs.

Answer 7

Ketoacidosis can occur from prolonged ketogenesis

1. starvation
2. uncontrolled diabetes

Question 8

Give examples of diseases associated with impaired fatty acid oxidation.

Answer 8

Deficiencies in B-oxidation result in hypoglycemia due to inability to support glucose.

• CPTI deficiency
• Medium chain acyl-dehydrogenase deficiency

Question 9

Determine how the process of β-oxidation and gluconeogenesis are interconnected.

Answer 9

Supplies high levels of ATP even in fasted state.
ATP is required for:
- nitrogen disposal via UC
- glucose synthesis via GNG