(L5) Lipid Metabolism pt. 2

Question 1

What is the most energy dense fuel used by the body?

L5 S40 LO4

Answer 1

TAGs which are contain about 6.75 times as much energy as carbohydrates

Question 2

Where do TAGs come from?

L5 S45 LO4

Answer 2

• intestines (dietary)
• liver (de novo)
• adipocytes (de novo)

Question 3

How are TAGs synthesized in the intestine?
What promotes this?

L5 S48 LO4

Answer 3

Dietary TAGs are broken down into MAG and FFA in the intestine and are absorbed by intestinal cells.

TAGs are reassembled in intestinal cells.

TAGs are packaged with other lipids to form chylomicrons which are released into the lymph.

Promoted by dietary TAGs.

Question 4

How are TAGs synthesized in the liver?
What promotes this?

L5 S49;51 LO4

Answer 4

Glycerol 3-P is produced via glycerol kinase (only found in the liver) or from DHAP.

Synthesized FAs are then attached to the glycerol to form TAGs.

TAGs are packaged with other lipids to form VLDLs which are released into the blood.

Promoted by excess carbohydrates

Question 5

How are TAGs synthesized in adipocytes?

L5 S55 LO4

Answer 5

Glycerol 3-P formed from DHAP (from glycolysis).

Synthesized FAs are then attached to the glycerol to form TAGs.

TAGs are stored in adipocytes.

Question 6

What are the enzymes responsible for TAG breakdown?

L5 S56-57 LO5

Answer 6

• Adipose triglyceride lipase (ATGL)
• Hormone sensitive lipase (HSL)
• Lipoprotein lipase (LPL)
• MAG lipase

Enzymes are mostly non-specific with regards to TAG, DAG or MAG

Question 7

How are FAs transported for further degradation after being broken down from TAGs?

L5 S57-58 LO5

Answer 7

Small chains FAs (<6C) are transported freely in blood

Long chain FAs (>6C) are transported bound to albumin in the blood

Question 8

What are the major regulators of mobilization of fatty acids?

L5 S60 LO5

Answer 8

HSL is regulated

Promoted by hunger and exercise signaled by:

• glucagon
• epinephrine

Inhibited by fed state signaled by:
-insulin

Question 9

What is perilipin and what regulates it?
What is a possible clinical significance of perlipin?

L5 S62 LO5

Answer 9

Proteins that coat lipid droplets and regulate lipolysis

Regulated by PKA and PP1

PKA phosphorylates allowing access for lipolysis enzymes (HSL)
PP1 dephosphorylates reversing this

Could potentially be a target for obesity.

Question 10

What are the main steps of fatty acid breakdown and where does each step take place?

L5 S65 LO6

Answer 10

Transport and activation of fatty acid (cytosolic)

Beta-oxidation (mitochondrial)

Question 11

What is fatty acyl-CoA synthase and what is it the mechanism?

L5 S66;68 LO6

Answer 11

Converts fatty acid to FA-CoA using ATP and CoA.

Question 12

What is carnitine palmitoyltransferase I (CPT-I)?

L5 S66;68 LO6

Answer 12

RATE LIMITING for FA breakdown

Transfers FA from FA-CoA to carnitine to for FA-carnitine

Mitochondrial inner membrane is impermeable to FA-CoA

Question 13

What is carnitine-acyl carnitine translocase (CACT)?

L5 S66;68 LO6

Answer 13

Antiporter for FA-carnitine (into mitochondrial matrix) and carnitine (out of mitochondrial matrix)

Question 14

What is carnitine palmitoyltransferase II (CPT-II)?

L5 S66;68 LO6

Answer 14

Transfers FA from FA-carnitine to CoA releasing carnitine

Question 15

What are the 4 steps of β-oxidation and what enzyme catalyzes each step?

L5 S71 LO6

Answer 15

• oxidation (acyl CoA dehydrogenase)
• hydration (enoyl CoA hydratase)
• oxidation (3-hydroxyacyl CoA dehydrogenase)
• thiolysis (acetyl CoA acetyltransferase)

Question 16

What molecules are produced by fatty acid break down that are used to generate energy?

L29 S23

Answer 16

• FADH2 (2 ATP through complex 2)
• NADH (3 ATP through complex I)
• Acetyl CoA (through TCA cycle)

Question 16

How much ATP is generated by breaking down palmitic acid (16C)?

L29 S24

Answer 16

• 7 FADH2 x 2 ATP (14 ATP)
• 7 NADH X 3 ATP (21 ATP)
• 8 acetyl CoA x 12 ATP (96 ATP)

Minus 2 ATP used during breakdown
——————————————————
Net ATP 129

Question 16

What molecule is needed for acetyl CoA to be used in the TCA cycle?

L29 S25

Answer 16

Oxaloacetate is needed with acetyl CoA for used by citrate synthase.

Low carb will result in low acetyl CoA

Question 16

What is MCAD and what is the clinical significance of it?

L5 S72 LO6

Answer 16

MCAD - medium chasing acyl CoA dehydrogenase, it is a type of ACAD (first step of FA degradation

It is the most commonly genetically defective enzyme of this pathway

Question 16

How are odd number FAs degraded?

L5 S76 LO7

Answer 16

Degraded normally until propionyl-CoA (3C)

This is carboxylated to and then converted to succinyl-CoA which enters TCA cycle

Question 17

How are unsaturated FAs degraded?

L5 S77 LO7

Answer 17

Reductases removes double bonds

Isomerases moves disruptive double bonds

Question 19

What are ketone bodies, where are they produced and what are they used for?

L5 S85-86 LO9

Answer 19

Ketone bodies:

• acetoacetate
• β-hydroxybutyrate
• acetone

Produced in the liver through excessive β-oxidation induced by fasting/starving state

Provide energy in peripheral tissues during fasting condition and for the brain during starvation

Question 20

What fuel sources are used during fasting and starvation and at what times are they used?

L5 S90 LO9

Answer 20

Glucose (from last meal)
Glycogen (<1 day)
TAGs (1 day)
Ketones and AAs enter gluconeogenesis (3 days)
Brain uses ketones directly (1-2 weeks)
Proteins only remaining source (2-3 months)

Death follows

Question 21

What is the difference in physiological and pathological ketoacidosis?

Answer 21

Physiological:

• mild to moderate increase in ketone bodies
• occurs in fasting pregnant women and following prolonged exercise

Pathological:

• increased glucagon/insulin ratio
• increased acetyl CoA results in reduced oxaloacetate, favoring ketone production

Question 22

What is peroxisomal β-oxidation?
What is significant about?

L5 S78-79 LO7

Answer 22

Used in degradation of very long chain FAs.

Produces hydrogen peroxide
Does not produce ATP