Lipid Metabolism

Question 1

Functions of lipids

Answer 1

Fuel stores (provide energy)
Structural components of plasma membranes
Signaling molecules (participate in pathways that regulate growth, survival and immune response)
Other roles include providing insulation, generating heat and fat digestion

Question 2

What is the major source of carbon for FA synthesis?

Answer 2

Dietary carbohydrates

Question 3

What are the major steps in FA synthesis?

Answer 3

Phase 1: cytosolic entry of acetyl CoA
Phase 2: generation of malonyl CoA
Phase 3: FA chain formation

Question 4

What is the RLE for FA synthesis?

Answer 4

Acetyl CoA carboxylase which converts acetyl CoA to malonyl CoA

Question 5

What are the reactions catalyzed by FAS?

Answer 5

Condensation, reduction, dehydration, reduction and product release

Question 6

Synthesis of longer chain FAs (elongation)

Answer 6

Palmitate converted to longer chain FA in SER or mitochondria
Brain cells need longer chain FAs (C18-24)
FA lengthened 2 carbons at a time
NADPH used as reducing power

Question 7

The SER pathway of FA elongation uses what as the carbon donor?

Answer 7

Malonyl CoA

Question 8

The mitochondrial pathway of FA elongation uses what as the carbon donor?

Answer 8

Acetyl CoA

Question 9

Where does desaturation/unsaturation occur?

Answer 9

In the SER and it uses NADPH/NADH and oxygen

Catalyzed by acyl CoA desaturases

Question 10

How many desaturases do humans have?

Answer 10

Four: delta 4, 5, 6 and 9 that cannot make a double bound beyond carbon 9 (C9-10) and the methyl end
Ex. Omega 3 and 6 FAs (which is why they need to be in the diet)

Question 11

What are the essential FAs?

Answer 11

Linoleic (18:2 omega 6) and linolenic acid (18:3 omega 3)

Question 12

What is linoleic acid used to make?

Answer 12

Arachidonic acid (omega 6) a precursor for eicosanoids (prostaglandins, leukotrienes and thromboxanes)

Question 13

What is linolenic acid used to make?

Answer 13

Eicosapentaenoic acid (EPA omega 3) and docosahexanoic acid (DHA omega 3)

Question 14

What is the storage form of FA?

Answer 14

TAGs

Question 15

What are the 4 major lipases?

Answer 15

ATGL (adipose triglyceride lipase), hormone sensitive lipase (HSL), lipoprotein lipase (LPL) and monoacylglycerol lipase (MAG lipase)

Question 16

The activity of HSL is modulated by what?

Answer 16

Phosphorylation

Question 17

What two major signals promote mobilization of TAGs?

Answer 17

Hunger and exercise

Question 18

What are the major controllers of the signaling that promotes mobilization of TAGs?

Answer 18

Glucagon (secreted in response to hunger) and epinephrine (secreted in response to exercise)
Both phosphorylate HSL (activate) and promote lipolysis in adipocytes

Question 19

What inhibits the mobilization of TAGs?

Answer 19

Fed status

Insulin (secreted in response to a high carb meal) dephosphorylates HSL via activation of PP1 to inhibit lipolysis

Question 20

What are perilipin?

Answer 20

A family of proteins that coat lipid droplets in adipocytes and muscle cells
Regulate lipolysis by controlling physical access to HSL
They are regulated by PKA (phosphorylation allows association with HSL) which promotes lipolysis

Question 21

What are the major steps in FA oxidation?

Answer 21

Phase I: transport of FA into the mitochondria

Phase II: beta oxidation

Question 22

What are the 4 major steps of beta oxidation?

Answer 22

Oxidation, hydration, oxidation and thiolysis

Question 23

CPT I deficiency

Answer 23

Defect in the catabolism of FAs
Defect in carnitine palmitoyltransferase I (CPT I)
Associated organelle: mitochondria

Question 24

CACT deficiency

Answer 24

Defect in the catabolism of FAs
Defect in carnitine acylcarnitine translocase (CACT)
Associated organelle: mitochondria

Question 25

CPT II deficiency

Answer 25

Defect in the catabolism of FAs Defect in carnitine palmitoyltransferase II (CPT II) Associated organelle: mitochondria

Question 26

MCAD deficiency

Answer 26

Defect in the catabolism of FAs Defect in medium chain acyl CoA dehydrogenase (MCAD) Associated organelle: mitochondria

Question 27

Zellweger syndrome

Answer 27

Defect in biogenesis of peroxisomes (affects FA catabolism)

Question 28

Infantile Refsum disease

Answer 28

Defect in assembly of peroxisomes (affects FA catabolism)

Question 29

X-linked adrenoleukodystrophy

Answer 29

Defect in transport of very long chain FAs into peroxisomes

Question 30

Adult Refsum disease

Answer 30

Defect in the catabolism of FAs Defect in degradation of phytanic acid Associated organelle: peroxisome

Question 31

Describe MCAD deficiency (detailed)

Answer 31

Disorder of beta oxidation that impairs breakdown of MCFAs Leads to secondary carnitine deficiency due to excessive excretion of MCA carnitine in urine Pts depend on glucose as energy source Gluconeogenesis impaired due to low activity of pyruvate carboxylase due to low ATP & acetyl CoA

Question 32

What are the 3 important KBs?

Answer 32

Acetoacetate, beta hydroxybutyrate and acetone

Question 33

Where are KB produced?

Answer 33

In the liver ONLY

Question 34

What are the sources of NADH that are used as a reducing power for FA synthesis?

Answer 34

Malic enzyme and PPP