Class 6: Lipid Metabolism 2

Question 1

What is the major source of carbon for FA synthesis?

Answer 1

Dietary carbohydrate

Question 2

Where does FA synthesis primarily occur?

Answer 2

In the liver

Also occurs in brain, kidney, and adipose tissue

Question 3

MAjor steps in FA synthesis:

Answer 3

1. Formation of acetyl CoA
2. Conversion of acetyl CoA to Malonyl CoA
3. Elongation (addition of carbons)
4. Desaturation (introduce of double bonds)

Question 4

Citrate lyase

Answer 4

Lyses citrate to OAA and produces Acetyl CoA—supplies carbons for FA synthesis.

Question 5

Malic enzyme

Answer 5

Converts malate to pyruvate

Question 6

Citrate lyase and malic enzyme make up the:

Answer 6

Synthesis of acetyl CoA

Question 7

What is the rate limiting step in FA biosynthesis?

Answer 7

Acetyl CoA carboxylase (ACC)

Acetyl CoA converted to Malonyl coa by carboxylation-adds CO2 (req’s biotin and ATP)

Question 8

Regulation of ACC:

Answer 8

Allosteric:
+ Citrate
-long chain FA

Phosphorylation:
+ insulin
- epinephrine/glucagon

Induction:
+up-regulated w/ high carbohydrate diet
- down-regulated by high fat diet

Question 9

2 carbon units from Malonyl CoA are sequentially added to growing fatty acyl chain to form palmitate.

Reacitons of FA synthesis occur on the:

Answer 9

Fatty acid synthase complex

Question 10

2 identical dimers, each has 7 catalytic activities and an Acyl carrier protein (ACP),

Answer 10

FAS. Fatty acid synthase

Question 11

ACP has a flexible arm w/ _____________________ group.

Answer 11

phosphopantetheine

Question 12

Palmitate synthesis req’s:

Answer 12

8 acetyl CoA, 7 ATP, 14 NADPH,

Question 13

Regulation of fatty acid synthase complex (FAS):

Answer 13

Allosteric:
(Presence of phosphorylated sugars)

Induction:
+high carb diet increases FAS synthesis
-high fat diet

Question 14

Creating unsaturation stipulations:

Answer 14

Cant introduce double bonds beyond C-9…Cant synthesize linoleate and linolenate

That’s why theyre EFAs

Question 15

Products generated by oxidation of 20 carbon FAs (arachidonic acid)

Answer 15

Eicosanoids

Serve as messenger and signaling molecules.

Serve as local hormones.

4 families: prostaglandins, prostacyclins, thromboxanes, and leukotrienes.

Question 16

Aspirin blocks effects of:

Answer 16

Eicosanoids– prostaglandins

Question 17

Mechanism 1 of phospholipid synthesis:

Answer 17

1. Phosphatidic acid cleaved by phophatase to form DAG
2. Head groups activated w/ CTP and become CDP-head grp which can react w/ DAG.
3. After reaction, CMP is released and glycerophospholipid is formed

-phosphatidylcholine (PC) and phosphatidyethanolamine (PE)

Question 18

Mechanism 2 of phospholipid synthesis:

Answer 18

1. Phosphatidic acid reacts w/ CTP to form CDP-DAG.
2. CDP-DAG reacts w/ head group, and releases CMP.
3. Glycerophospholipid is formed

-phosphaidylinositol (PI) and cardiolipin

Question 19

Most abundant sterol.
Component of membranes and precursor to vitamin D, bile salts, steroid hormones.
DAILY PRODUCTION: ~1 g, mostly in liver.
BIOSYNTHESIS REGULATED BY DIETARY INTAKE.

Answer 19

Cholesterol

Question 20

Alicyclics compound.

27 C’s, 4 fused rings, 1 double bond btw C5 and C6, 2 CH3 at C18 and C19, 1 OH at C3, 8 member hydrocarbon chain attached to C17

Answer 20

Cholesterol.

Question 21

Synthesis of cholesterol:

Answer 21

1. Acetyl CoA is beginning molecule.
2. It is reduced by HMG CoA Reductase(rate-limiting step-target of statins), which uses a NADPH.
3. One step req’s ATP after and 3 req’ NADPH to form cholesterol.

Question 22

The synthesis of __________ is a committed step in cholesterol formation.

Answer 22

Mevalonate

Question 23

What is the rate limiting enzyme in cholesterol synthesis?

Answer 23

HMG CoA synthase

Reduced acetyl CoA to mevalonate

Question 24

OH at C3 on cholesterol can become “cholesterol ester” by means of :

Answer 24

Acyl CoA acyl transferase (ACAT)

-extremely hydrophobic stored in lipid droplets(VLDL)

Question 25

Lipoproteins:

• Largest
• least dense
• high TAG content

Answer 25

Chylomicron

Question 26

VLDL go to the liver. (ApoE)

IDL is degraded and goes to liver. (ApoE)

Why is LDL considered bad?

Answer 26

Densely packed w/ cholesterol.

Question 27

Lipoproteins:

• smallest
• most dense
• HIGH PROTEIN AND PHOSPHOLIPID CONTENT

Answer 27

HDL

This is why its considered good