Lipid Metabolism II (Lecture 1 - Exam 3) Flashcards

1
Q

Lipolysis

A

The breakdown of triglycerides and the mobilization of FAs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

HSL

A

Hormone Sensitive Lipase

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Perilipin

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Adipose triglyceride lipase (ATGL)

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Monoacylglycerol lipase (MGL)

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are the 5 steps of LIPOLYSIS?

A
  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.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What happens to the FFAs after lipolysis?

A

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.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What happens to the glycerol molecule after lipolysis?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

How is HSL regulated?

A

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)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

(TRUE/FALSE)

Fatty acids must be activated.

A

TRUE

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Acyl CoA synthetase

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

How are FAs activated?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

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

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

2.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

CPT1

A

Carnitine palmitoyl transferase 1

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

How does the LCFA cross the inner mitochondrial membrane?

A

Via Translocase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

CPT2

A

Carnitine Palmitoyl transferase 2

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

17
Q

How is carnitine recycled?

A

Via Translocase

18
Q

(TRUE/FALSE)

Shorter chain FAs cross the mitochondrial membrane independent of CPT1.

A

TRUE

19
Q

Where does beta-oxidation occur?

A

Mitochondrial Matrix

20
Q

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

A
  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.

21
Q

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

A

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)

22
Q

How many ATP does FADH yield?

A

3 ATP

23
Q

How many ATP does NADH yield?

A

2 ATP

24
Q

How many ATP does acetyl CoA yield?

A

12 ATP

25
Q

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

A

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
26
Q

What are the hormones and enzymes involved in lipolysis

A

Hormones: EPINEPHRINE, HSL

Enzymes: Protein Kinase A, Perilipin, ATGL, MGL

27
Q

Following lipolysis, what happens to glycerol and FFAs?

A

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

28
Q

How do FFAs translocate into the mitochondria from the cytoplasm?

A

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.

29
Q

What is beta-oxidation?

A

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.

30
Q

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

A

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***

31
Q

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

A

1) Enter the Kreb’s Cycle

2) Ketone synthesis

32
Q

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

A

FADHs: CoQ

NADH: Complex I

Both will undergo oxidation in the ETC.

33
Q

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

A

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