Lipid Metabolism

Question 1

What are the 4 functions of lipids?

Answer 1

1. energy storage
2. structural components
3. Signaling molecules.
4. Others: insulation, heat…

Question 2

What are the types of Fatty Acid Derivatives?

Answer 2

1. glycerol backbone (mono-, di- and tri-acylglycerols)
2. : 2 fatty acids attached to a glycerol backbone. phosphate esterified with a head group (e.g., phosphatidylcholine, phosphatidylserine)

The other non-FA derivative is isoprenoids (cholestrol/steroids)

Question 3

What is the Major source of carbon for fatty acid synthesis?

Answer 3

Carbs

Question 4

What organ does Fatty acid synthesis occur in?

Answer 4

Liver: requires cytosolic and mitochondrial coordination for reactions

Question 5

What is the foundational unit of FA synthesis?

Answer 5

Acetyl-Coa

Question 6

What is the first phase of FA synthesis?

Answer 6

Cytosolic entry of Acetyl CoA

Made in mitochondrial matrix but needed in cytoplasm

Question 7

What is the second phase of FA synthesis?

Answer 7

Generation of Malonyl CoA

Acetyl CoA is carboxylated to malonyl CoA. Most important substrate in FA synthesis. Rate limiting reaction

Question 8

What is the third phase of FA synthesis?

Answer 8

Fatty acid chain formation
(The enzyme Fatty acid synthase catalyzes 7 reactions that incorporate Acetyl CoA and Malonyl CoA into palmitate, a C16 fatty acid)

Question 9

What is the rate limiting step of Fatty Acid synthesis?

Answer 9

Acetyl-Coa carboxylase (needs biotin)

Question 10

What are the activators of ACC?

Answer 10

Citrate, Insulin

Question 11

What is the reaction that ACC carries out?

Answer 11

ACC carboxylates actetyl-CoA into malonyl-coA and uses 1 ATP and biotin as a cofactor.

Question 12

What inhibits ACC?

Answer 12

Glucagon, Epinephrine, high AMP, palmitate, PUFA.

Question 13

Explain the regulation of glucagon and epinephrine involving phosphorylation of ACC and how it affects FA synthesis.

Answer 13

Glucagon and epinephrine cause PKA to PO4 ACC, which INACTIVATES it. INHIBITING ACC = NO FA SYNTHESIS

Question 14

Explain the regulation of insulin involving phosphorylation of ACC and how it affects FA synthesis.

Answer 14

Insulin stimulates protein phosphatase-1 (PP1) mediated dephosphorylation of ACC, which ACTIVATES IT, thus making FA synthesis on.

Question 15

What is the Substrate for Fatty Acid Synthase (FAS)

Answer 15

Malonyl-coA

Question 16

What is the main regulator in FA degradation?

Answer 16

Malonyl-coA

Question 17

Where does elongation of fatty acids occur?

Answer 17

Smooth ER, uses malonyl-CoA as a carbon donor

Question 18

Where does desaturation of FAs occur?

Answer 18

Smooth ER, use Acyl-CoA desaturases

Question 19

How many desaturases do humans have and where can they introduce double bonds?

Answer 19

They can introduce double bonds between carbons 4-5, 5-6, 6-7, and 9-10 of the fatty acid.

FA with double bond beyond carbon 9 and 10 cannot be synthesized in humans

E.g., Omega 3 fatty acids and Omega 6 fatty acids
Need to ingest them or their precursors in diet
Precursors called Essential Fatty Acids

Question 20

How are desaturases regulated?

Answer 20

Insulin and suppressed by dietary PUFAS (polyunsaturated fatty acids)

Question 21

What are the essential fatty acids and why can’t they be made?

Answer 21

Linoleic acid (18:2 ω6):  used to make arachidonic acid 
Linolenic acid (18:3 ω3): used to make eicosapentanoic acid (EPA) (20:5  ω3) and docosahexanoic acid (DHA)

Question 22

What are essential fatty acids?

Answer 22

Human desaturases cannot introduce double bonds beyond C9, which is why they are essential fatty acids.