Lipid Metabolism

Question 1

Glycerolipids

Answer 1

glycerol backbone + FA

Question 2

Glycerophospholipids

Answer 2

glycerol backnone + 2 FAs + phosphate head group

Question 3

Phase 1 of FA synthesis

Answer 3

Cytosolic Entry of Acetyl CoA: in the mitochondrial matrix, OAA + acetyl CoA can be converted to citrate, which can then be shuttle out of mitochondria into cytosol where it can be converted back to OAA via ATP citrate lyase. (+ glucose and insulin, - leptin and PUFA). As citrate is converted back to OAA, CoA + ATP is converted back to Acetyl-CoA to enter FA synthesis. OAA can then be converted back to malate and reenter mitochondria there or go to pyruvate and reeneter mitochondria.

Question 4

Phase II of FA synthesis

Answer 4

Now acetyl CoA is free in cytoplasm. Acetyl CoA -> Malonyl CoA via Acetyl CoA carboxylase (ACC).

Question 5

Rate limiting step of FA synthesis and coenzyme

Answer 5

ACC! and Biotin (B7)

Question 6

Activators and inhibitors of ACC

Answer 6

Active when dephosphorylated and inactive when P
+: insulin (activates PPI), citrate (allosterically)
-: PUFA (allosterically), glucagon (PKA), epinephrine (PKA), high AMP (activates AMP kinase)

Question 7

Malonyl CoA inhibits what?

Answer 7

Carnitine acyltransferase (rate limiting step for FA degradation)

Question 8

Phase III of FA synthesis

Answer 8

Two units of Malonyl CoA are added to growing fatty acyl chain in 7 reactions to form palmitate (16:0) via Fatty acid synthase.

Question 9

Structure of FA synthase

Answer 9

7 enzymatic subunits and acyl carrier protein (ACP)

Question 10

Stoichiometry of Palmitate synthesis

Answer 10

1 acetyl CoA + 7 malonyl CoA + 14 NADPH + 14 H+ = Palmitate + NADP + 8 CoA + 6 H20

Question 11

Reactions of FA synthase

Answer 11

Condensation, Reduction, Dehydration, Reduction X 6

Then product release

Question 12

Regulation of ATP Citrate Lyase

Answer 12

Stimulated by Phosphorylation. Gene expression is induced by glucose and insulin. PUFAs and Leptin counteract gene expression.

Question 13

Regulation of FA synthase

Answer 13

Insulin, glucocorticoid hormones, and high carb/low fat diet increase synthesis.
High fat diets and high PUFA suppress synthesis.

Question 14

Leptin mechanism

Answer 14

Leptin is secreted in direct proportion to fat mass that acts on leptin receptor in hypothalamus. When fat mass is high leptin is secreted to suppress food intake

Question 15

Elongation of Palmitate occur where ?

Answer 15

Smooth ER or mitochondria and uses NADPH as reducing power. SER uses malonyl CoA as carbon donor and Mitochondria uses Acetyl CoA as carbon doner

Question 16

How is desaturation done?

Answer 16

By Acyl CoA desaturases: humans have 4 - ∆4, ∆5, ∆6, and ∆9. FA’s with double bonds beyond carbon 9 and 10 cannot be synthesized in humans -> essentail FA such omega 3 and omega 6 FA.

Question 17

Regulation of Desaturases

Answer 17

Insulin induces gene expression and PUFAs suppress expression.

Question 18

Essentail FAs

Answer 18

Humans need to ingest omega 3 and omega 6 FAs. Linoleic acid is used to make arachidonic acid and linolenic acid is used to make EPA and DHA