Lipid Metabolism II

Question 1

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

Answer 1

dietary carbohydrates

Question 2

where does fatty acid synthesis primarily occur?

Answer 2

liver

Question 3

where does fatty acid synthesis also occur?

Answer 3

brain, kidneys, and adipose tissue

Question 4

List the components located in cytoplasm

Answer 4

– Enzymes
– Acyl carrier proteins
– Co-factors
– Reducing power
– Energy (ATP)

Question 5

List major steps in fatty acid synthesis.

Answer 5

Formation of Acetyl CoA
 Conversion of Acetyl CoA to Malonyl CoA
 Elongation (addition of carbons)
 Desaturation (introduction of double bonds)

Question 6

What is the rate limiting step of fatty acid synthesis?

Answer 6

Conversion of Acetyl CoA to Malonyl CoA

Question 7

What is the rate limiting step of fatty acid synthesis catalyzed by?

Answer 7

Acetyl CoA carboxylase (ACC)

Question 8

How is Acetyl CoA converted to malonyl CoA?

Answer 8

carboxylation

Question 9

How is ACC regulated?

Answer 9

• Allosteric regulation
• Citrate (+)
• Long chain fatty acids (-)
• Phosphorylation (-)/Dephosphorylation (+)
• Insulin (+)
• Epinephrine (-)
• Glucagon (-)
• Induction/repression
• Gene expression up-regulated by high carbohydrate/low fat diet
• Gene expression down-regulated by high fat/low
carbohydrate diet

Question 10

Describe Elongation of Fatty Acids.

Answer 10

• Two carbon units from malonyl CoA are
sequentially added to the growing fatty acyl chain to form palmitate (16:0).
• The reactions of fatty acid synthesis occur on the Fatty Acid Synthase Complex.

Question 11

What is Fatty Acid Synthase (FAS)?

Answer 11

• Large multi-enzyme complex.
• Composed of 2 identical dimers (260 kDa each).
• Each has 7 catalytic activities and an acyl carrier protein (ACP).
• ACP segment has a phosphopantetheine (PP) residue.
• Two dimers arranged in head to tail conformation - PP
of one is aligned with a cysteinyl sulfhydryl group of
another.

Question 12

List the reactions of fatty acid synthesis.

Answer 12

acetyl ACP to malonyl ACP to acetoacetyl ACP to D-3-hydroxbutyryl ACP to crotonyl ACP to butryryl ACP

Question 13

How is FAS regulated?

Answer 13

• Allosteric effect (presence of phosphorylated sugars)
• Induction and repression at gene level
– High carbohydrate/low fat diet increases FAS synthesis.
– High fat diet as well as starvation lowers FAS
synthesis.

Question 14

Describe Eicosanoids.

Answer 14

• Eicosanoids are products generated by the oxidation of 20-carbon fatty acids (arachidonic acid).
• They are signaling molecules and serve as messenger
molecules.
• Short lived molecules, serve as local hormones
• Influence many pathways involved in growth, inflammation, infection, and immunity

Question 15

What are the four families of eicosanoids?

Answer 15

Prostaglandins, prostacyclins, thromboxanes and

leukotrienes,

Question 16

What does PGD2 do?

Answer 16

promotion of sleep

Question 17

What does PGE2 do?

Answer 17

smooth muscle contraction; inducing pain, heat, fever; bronchoconstriction

Question 18

What does PGE2alpha do?

Answer 18

uterine contraction

Question 19

What doesTXA2 do?

Answer 19

stimulation of platelet aggregation; vasoconstriction

Question 20

What does PGI2 do?

Answer 20

inhibition of platelet aggregation; vasodilation; embryo implantation

Question 21

What does LTB4 do?

Answer 21

leukocyte chemotaxis

Question 22

Describe mechanism 1 for phospholipid synthesis.

Answer 22

 Phosphatidic acid cleaved by phosphatase to form
diacylglycerol (DAG).
 DAG reacts with various headgroups to form different
phospholipids.
 The headgroups need to be ‘activated’ prior to this
reaction.
 Choline headgroup combines with CTP to form CDPcholine (activated).
 Phosphocholine (PC) transferred to DAG to form
phosphatidylcholine and CMP is released.

Question 23

Describe mechanism 2 for phospholipid synthesis.

Answer 23

 Phosphatidic acid reacts with CTP to form CDP-DAG.
 CDP-DAG reacts with inositol to form PI and CMP.
 CDP-DAG may react with glycerol to produce
phosphatidyl glycerol.
 The reaction of CDP-DAG with phosphatidyl glycerol
forms diphosphatidyl glycerol (cardiolipin), a component
of the inner mitochondrial membrane.

Question 24

List the Interconversion between PLs.

Answer 24

 PS is formed by exchanging ethanolamine for serine.
 PS can be reconverted to PE by decarboxylation.
 PE can be methylated to form PC.

Question 25

Describe Cholesterol

Answer 25

Most abundant sterol (~ 0.05% of total body weight).
 Component of membranes and precursor of biologically active compounds:
 Bile acids and bile salts
 Vitamin D
 Steroid hormones (progesterone, aldosterone, cortisol, testosterone, estradiol)
 Daily intake: ~250 mg (~30-60% absorbed in gut).
 Daily production: ~1g, mostly in liver.
 Daily excretion: ~5% excreted, ~95% re-absorbed.
 Biosynthesis regulated by dietary intake.

Question 26

How many nobel prizes have been awarded to scientists

who devoted major parts of their careers to cholesterol?

Answer 26

13

Question 27

Describe the Structure of Cholesterol

Answer 27

 Allicyclic compound made of 4 fused rings
 Has 27 carbons, 4 rings, 1 double bond between C5
and C6, 2 CH3 at C18 and C19, 1 OH at C3, 8
member hydrocarbon chain attached to C17

Question 28

List the steps of Cholesterol Biosynthesis

Answer 28

acetyl CoA to mevalonate to squalene to dimethylallylpyrophosphate to lanosterol to cholesterol

Question 29

What does Oxidosqualene cyclase do?

Answer 29

• holds molecule into place and initiates protonation

Question 30

Describe HDLs

Answer 30

smallest and dense; high protein and phospholipid content