Lipid Metabolism II (Lecture 1 - Exam 3)

Question 1

Lipolysis

Answer 1

The breakdown of triglycerides and the mobilization of FAs

Question 2

HSL

Answer 2

Hormone Sensitive Lipase

Acts on the diacylglycerol molecule, producing another FFA and a monoacylglycerol remains

Question 3

Perilipin

Answer 3

The lipid coating that is around the triglyceride itself; it protects the droplet from HSL from hydrolyze the FAs.

When it is PHOSPHORYLATED, it allows the lipid droplet to be accessible by HSL

Question 4

Adipose triglyceride lipase (ATGL)

Answer 4

The first enzyme that acts on the TG, to produce the first FFA, with diacylglycerol remaining

Question 5

Monoacylglycerol lipase (MGL)

Answer 5

Acts on the monoacylglycerol molecule in the final step of lipolysis to produce the third FA and a glycerol molecule

Question 6

What are the 5 steps of LIPOLYSIS?

Answer 6

1. Epi binds to beta-adrenergic receptor and stimulates adenylate cyclase and cAMP is formed
2. cAMP activates protein kinase A
3. Protein kinase A phosphorylates and activates HSL and perilipin. Perilipin protects lipid droplet from HSL but when phosphorylated it allows ATGL to act on TAG producing FA and DAG
4. HSL acts on DAG to produce MAG and FA
5. MGL acts on MAG to produce FA and glycerol.

Question 7

What happens to the FFAs after lipolysis?

Answer 7

They will leave the tissue and be bound to albumin to be taken to peripheral tissue (muscle), where energy (ATP) is needed.

Remember- this is a FASTED state.

Question 8

What happens to the glycerol molecule after lipolysis?

Answer 8

It will go back to the liver to be either:

-Synthesized back into a triacylglycerol (via endogenous de novo synthesis)
-Participate in gluconeogenesis
-Ketone formation during a prolonged fast or starvation

Question 9

How is HSL regulated?

Answer 9

Hormonally:

1. Epinephrine will lead to the phosphorylation of HSL via cAMP and activation
2. INSULIN will dephos and inactivate HSL, as it activates phosphatase enzyme. It also reduces the expression of ATGL (decreasing lipolysis in general)

Question 10

(TRUE/FALSE)

Fatty acids must be activated.

Answer 10

TRUE

Question 11

Acyl CoA synthetase

Answer 11

Combines the LCFA with CoA to form LC fatty acyl CoA within the cytosol.

This activates the FA, allowing it to cross the outer mitochondrial membrane

Question 12

How are FAs activated?

Answer 12

Via the enzyme Acyl CoA synthetase which is located on the outer mitochrondrial membrane

This allows LC fatty acyl CoA to cross the outer mito. membrane

Question 13

What are the steps of LCFA crossing the inner mitochondrial membrane?

Answer 13

1. FAs are activated to FA CoA via Acyl CoA Synthetase and cross the OUTER mito membrane

2.

Question 14

CPT1

Answer 14

Carnitine palmitoyl transferase 1

An outer mito. membrane bound enzyme that cleaves off CoA and attaches carnitine to the FA

Question 15

How does the LCFA cross the inner mitochondrial membrane?

Answer 15

Via Translocase

Question 16

CPT2

Answer 16

Carnitine Palmitoyl transferase 2

An INNER mito membrane bound enzyme that binds, removes carnitine and adds CoA to reform FA CoA

Question 17

How is carnitine recycled?

Answer 17

Via Translocase

Question 18

(TRUE/FALSE)

Shorter chain FAs cross the mitochondrial membrane independent of CPT1.

Answer 18

TRUE

Question 19

Where does beta-oxidation occur?

Answer 19

Mitochondrial Matrix

Question 20

What are the steps of beta-oxidation of LCFA even numbered carbon chain?

Answer 20

1. Fatty acyl CoA –> trans-2-enoyl CoA via dehydrogenase, which introduces a double-bond between C2 & C3 and produces FADH2
2. Trans-2-enoyl CoA —-> 3-Hydroxacyl CoA via Hydratase, which adds a H20 and OH group between C2 and C3
3. 3-Hydroxacyl CoA —> 3-Ketoacyl CoA via Dehydrogenase, which introduces a double bond and produces NADH
4. 3-Ketoacyl CoA —> Fatty acyl CoA + Acetyl CoA via Thiolase, C2 & C3 are cleaved off, CoA is attached to form acetyl CoA.

Acetyl CoA can then proceed to the Kreb’s Cycle or be used to synthesize ketones

This 4 step process starts over.

Question 21

For 16 carbon fatty acid, palmitate, what is the energy yield from beta-oxidation?

Answer 21

In the first step, it will yield 1 FADH, 1 NADH, 1 Acetyl CoA (which will go to the Kreb’s Cycle and produce 12 ATP).

1 FADH = 3 ATP
1 NADH = 2 ATP
1 Acetyl CoA = 12 ATP
For a total yield for palmitate of 129 ATP (131 ATP - 2 ATP)

Question 22

How many ATP does FADH yield?

Answer 22

3 ATP

Question 23

How many ATP does NADH yield?

Answer 23

2 ATP

Question 24

How many ATP does acetyl CoA yield?

Answer 24

12 ATP

Question 25

What are the steps in beta-oxidation of odd number carbon FAs?

Answer 25

They are processed the SAME as the odd number, until propionyl-CoA is left (remember- this is a 3 carbon FA) 1. Propionyl-CoA ----> D-Methylmalonyl CoA via Carboxylase, where Biotin is required. 2. D-Methylmalonyl CoA ---> L-Methylmalonyl CoA via Methylmalonyl CoA RACEMASE, isomerization 3. L-Methylmalonyl CoA ---> Succinyl CoA via Methylmalonyl CoA MUTASE (which is VITAMIN B12 DEPENDENT) 4. Succinyl CoA enters into the Kreb's Cycle

Question 26

What are the hormones and enzymes involved in lipolysis

Answer 26

Hormones: EPINEPHRINE, HSL Enzymes: Protein Kinase A, Perilipin, ATGL, MGL

Question 27

Following lipolysis, what happens to glycerol and FFAs?

Answer 27

GLYCEROL: transported to the liver and used for endogenous TAG de novo synthesis, OR ketone formation (during a prolonged fast/starvation), OR part of gluconeogenesis FFA: leaves adipocytes and travels in the blood, bound to albumin, to be transported to the MUSCLE, to enter cells to be utilized as energy, in the form of ATP

Question 28

How do FFAs translocate into the mitochondria from the cytoplasm?

Answer 28

1) FAs are activated to FA-CoA by ACYL CoA SYNTHETASE and cross the OUTER mito. membrane. 2) CPT1 cleaves off CoA, attaches carnitine to FA & the complex crosses the INNER mito. membrane into the matrix via TRANSLOCASE 3) CTP2 binds, removes carnitine and adds CoA to reform FA-CoA 4) Carnitine is recycled via TRANSLOCASE **REMEMBER: SCFA cross mito. membrane w/o CPT1.

Question 29

What is beta-oxidation?

Answer 29

The major pathway for catabolism of FAs is a mitochondrial pathway, called beta-oxidation, in which 2-carbon fragments are successively removed from the carboxyl end of the fatty acyl CoA, producing acetyl-CoA, NADH, FADH.

Question 30

How many FADH2, NADH, and acetyl-CoA will be provided from a 16-carbon fatty acid (palmitate)?

Answer 30

7 NADH (2 ATP each) = 14 ATP 7 FADH (3 ATP each) = 21 ATP 1 Acetyl-CoA (12 ATP each) = 96 ATP EQUALS: 131 - 2 ATP = 129 ATP***

Question 31

What is the fate of acetyl-CoA from beta oxidation?

Answer 31

1) Enter the Kreb's Cycle 2) Ketone synthesis

Question 32

What is the fate of FADHs and NADH from beta-oxidation?

Answer 32

FADHs: CoQ NADH: Complex I Both will undergo oxidation in the ETC.

Question 33

How is beta-oxidation of odd number carbon fatty acids different from even number?

Answer 33

It is the same until you reach propionyl-CoA (3 carbon FA)