Met 1: Fatty Acid Oxidation

Question 1

What is the energy source for gluconeogenesis?

Answer 1

fatty acid oxidation

Question 2

Can triglycerides be substrate for gluconeogenesis?

Answer 2

Fatty acids CANNOT be turned into glucose (enter TCA cycle too late, as acetyl-coA)

Glycerol backbone can be converted to glucose

Question 3

How does fat get from adipose TG’s to target tissues?

Answer 3

1. Triglycerides in adipose tissue are broken down into free fatty acids and glycerol
   
   • by Hormone-Sensitive Lipase
2. Free fatty acids travel through blood bound to albumin to reach target tissues

Question 4

What is hormone-sensitive lipase?

Describe its regulation

Answer 4

Hormone sensitive lipase:

• Breaks TG’s into glycerol and free fatty acids.
• It’s active when glucagon is high (aka when it’s phosphorylated)

Question 5

Where in the cell does beta oxidation occur?

Answer 5

Inner mitochondrial matrix

Question 6

How do fatty acids get into the target tissue’s mitochondria?

Answer 6

1. In cytosol, fatty acid is activated to fatty acyl-coA
   
   • By fatty acyl coA synthase
2. Fatty acyl coA moves into mitochondrial intermembrane space
3. Fatty acyl coA then attached to carnitine
   
   • by carnitine acyltransferase-1
4. Fatty acyl carnitine can move into inner matrix
5. Carnitine is removed to yield fatty acyl coA

Question 7

What is the rate limiting step of fat oxidation?
Name one allosteric regulator

Answer 7

Rate-limiting step: Carnitine acyltransferase-1 (converting fatty acyl-coA into fatty acyl carnitine)

Regulation: CAT-1 is inhibited by malonyl-coA (part of lipid synthesis)

Question 8

Is carnitine used up during fat oxidation?

Answer 8

NO. It gets recycled

Carnitine gets attached to fatty acyl coA and then released from fatty acyl coA

Question 9

Describe the two steps of beta oxidation.

What is the enzyme, where does it occur?

Answer 9

1. Acyl coA dehydrogenase removes 2C at a time from fatty acyl-coA
   
   • in mitochondrial matrix
   • this produces FADH2, NADH, and acetyl-coA
2. Acetyl-coA goes into TCA cycle

Question 10

What are the products of beta oxidation?

Answer 10

Acetyl-coA

FADH2

NADH

Question 11

What is special about odd numbered fatty acids?

Answer 11

Odd numbered fatty acids can go into gluconeogenesis.

Question 12

How are odd numbered fatty acids used clinically?

Answer 12

• Metabolism of odd-# fatty acids requires B12
• If B12 deficiency -> buildup of methylmalonylcoA
• Methylmalonyl coA is thus a marker for B12 def

Question 13

What is another organelle (besides mitochondria) that can do beta oxidation?

Answer 13

Peroxisome

Question 14

What are the rate-limiting enzymes in lipid synthesis and beta oxidation?

How are they regulated hormonally?

Answer 14

• Lipid synthesis: acetylcoA carboxylase
  
  • Upregulated by insulin, inhibited by glucagon
• Lipolysis: hormone-sensitive lipase
  
  • upregulated by glucagon, inhibited by insulin

Question 15

Name 2 ketoacids

Answer 15

acetoacetate

beta-hydroxybutyrate

Question 16

When does ketone synthesis occur?

What will insulin/glucagon levels be?

Answer 16

When there is excess acetyl-coA, but increased NADH and ATP from fat oxidation is inhibiting the TCA cycle

(ie when fat is only fuel source)

High glucagon, low insulin

Question 17

In what tissues does ketone synthesis occur?

Where do ketones go to?

Answer 17

Ketone synthesis occurs in liver

Ketones transported to brain and muscle to be used as fuel (reconverted to acetyl-coA there)

Question 18

What are 3 conditions that can cause ketone synthesis?

Answer 18

• Diabetes
• Starvation
• Alcoholism

Question 19

Describe the two steps of ketone synthesis

Answer 19

1. Acetyl-coA converted to HMG coA
   
   • by HMG coA synthase
2. HMG coA converted to ketones

Question 20

Where in the cell does ketone synthesis occur?

Answer 20

Mitochondria matrix

(of liver cells)