Metabolism: Fatty Acids & Ketones

Question 1

What is the function of HSTL?

Answer 1

HSTL = hormone sensitive TAG lipase

- breaks down TAG into glycerol and FFAs

Question 2

What is the function of perilipin?

Answer 2

perilipin (LDAP) - lipid droplet associated protein

- required for HSTL mobilization and activation

Question 3

What are the sources of TAG?

Answer 3

• glucose => glycerol
• dietary lipids => chylomicrons
• TAG from the liver

Question 4

What are the activators of HSTL?

Answer 4

• epinephrine (cAMP => phosphorylation)
• ACTH
• thyroid hormones and adrenal corticol hormones (not required)

Question 5

What are inhibitors of HSTL?

Answer 5

• insulin

- prostaglandins

Question 6

What are the fates of FAs released by lipolysis?

Answer 6

• transported in circulation via association with albumin
• carried to muscle, liver, etc.
• used in beta-oxidation and energy production
• used in TCA or to make ketone bodies

Question 7

What are the fates of glycerol released by lipolysis?

Answer 7

• transported to liver and kidney

- used in gluconeogenesis after conversion to glycerol-3-phosphate

Question 8

What does FA release inhibit?

Answer 8

• inhibition of fatty acid synthesis (because you need to use up TAG not store it)
• inhibition of glycolysis (because you need to generate energy, not use it up)

Question 9

What does FA release activate?

Answer 9

• ketone body formation

- gluconeogenesis

Question 10

How does FA degradation inhibit glycolysis?

Answer 10

• generates lots of ATP

- ATP inhibits PFK1

Question 11

What is the major energy producing pathway in the body?

Answer 11

beta oxidation of FA

Question 12

Which organs mainly use fatty acids?

Answer 12

liver
kidney
heart
musclee

Question 13

Which organs cannot use fatty acids?

Answer 13

brain, CNS
RBCs
adrenal medulla
lens

Question 14

How much ATP does palmitate yield?

Answer 14

1 palmitate = 8 aCoA + 7 FADH2 + 7 NADH

106 ATP

Question 15

What is the function of carnitine?

Answer 15

transport of FAs into the mitochondrial matrix for beta oxidation

Question 16

Inhibition of carnitine transport can lead to what?

Answer 16

• inhibit FA oxidation

- decreased ATP production

Question 17

Describe the mechanism of carnitine.

Answer 17

1. CPT1 acts on fatty acyl-CoA and carnitine to produce acyl-carnitine
   NOTE: fatty acyl-CoA are outside the mitochondrial membrane and carnitine is on the inside of the mitochondria
2. CPT1 activity transfers the acyl group to be carried by carnitine
3. translocase enzyme brings acyl-carnitine inside the mitochondrial matrix
4. CPT2 transfers acyl to CoA to regenerate carnitine (sent out of the matrix) and acyl-CoA
5. acyl-CoA is then used for beta oxidation

Question 18

At which point in lipid metabolism does malonyl-CoA act upon?

Answer 18

malonyl-CoA inhibits CPT1

prevents attachment of acyl group to carnitine and prevents transport into mito matrix

Question 19

How does malonyl-CoA affect lipid metabolism?

Answer 19

• increased = promotes biosynthesis, inhibits beta oxidation (because you have lots of energy you need to store)
• decreased = promotes beta oxidation (because you don’t have enough energy)

Question 20

How does SIDS relate to lipid metabolism?

Answer 20

• deficiency in FA-CoA dehydrogenase enzyme

- prevents beta-oxidation

Question 21

List examples of ketone bodies.

Answer 21

acetone
acetoacetate
beta-hydroxybutyrate

Question 22

Describe the function of HMG-CoA Synthase and where it is active.

Answer 22

• only active in the liver

- eventually forms acetoacetate, which can further derivate to form acetone and beta-hydroxybutyrate

Question 23

What is unique about ketone bodies in the liver?

Answer 23

• ketone bodies are ONLY synthesized in the liver

- however, the liver can NOT utilize them for energy because it lacks succinyl-CoA transferase (thiophorase)

Question 24

What is the function of succinyl-CoA transferase?

Answer 24

converts ketone bodies to acetyl-CoA for use in energy production

Question 25

What is the rate limiting step in ketogenesis?

Answer 25

HMG-CoA Synthase

Question 26

How is TAG breakdown regulated?

Answer 26

activated by epi

inhibited by insulin