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BMIS 435 > Lipolysis > Flashcards

Lipolysis Flashcards

1
Q

What is lipolysis

A

Breakdown of TG stored in adipose tissue to fatty acids and glycerol
Fatty acids are then turned to ATP via B-oxidation in the mitochondria

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2
Q

What are lipases

A

break down ester bonds of triacylglycerol to release 3 FA

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3
Q

What are lipid droplets? What is the role of LD in adipocytes and structure?

A

Organelle that contains TG
TG storage in adipocytes
present in cytosol
Surface of phospholipids and proteins
Core of TG

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4
Q

T/F lipid droplet-associated proteins have specific functions

A

True

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5
Q

What is the most abundant lipid droplet protein

A

Perilipin

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6
Q

Function of perilipin

A

Forms a barrier around LDs
Prevents unwanted lipolysis

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7
Q

What is immunofluorescence microscopy

A

Visualize specific proteins in cells
allows you to see the location of a protein in a single cell

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8
Q

What happens to perilipin when lipolysis is activated

A

Perilipin undergoes a conformational change
Can access TG

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9
Q

Was the classic pathway of lipolysis correct? Why or why not

A

No
Though that HSL (hormone sensitive lipase) was responsible for every step from TG to glycerol, when HSL didn’t participate int he first step to DG.
It is a DG lipase

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10
Q

What is HSL

A

HSL is a DG lipase and is not the lipsae responsible for TG hydrolysis during lipolysis

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11
Q

What accumulates in HSL ko-mice

A

DG accumulated

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12
Q

All lipases have what motif?

A

GXSXG
(Serine is important for catalysis)

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13
Q

What was the enzyme that was found to be responsible for the first step of lipolysis?

A

Adipose Tissue Triacylglycerol Lipase (ATGL)

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14
Q

Where is ATGL present

A

Adipocytes

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15
Q

What happened in ATGL KO mice

A

TG lipase activity was reduced by 80%
Lipolysis was impaired

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16
Q

How is lipolysis measured

A

rate of fatty acid release into media

17
Q

What is isoproterenol

A

A drug that stimulates lipolysis when incubated with adipose
Mimics epinephrine

18
Q

What are the three lipases involved in lipolysis? Which enzyme is rate-limiting? Which enzyme needs to be activated?

A

ATGL: TG –> DG
HSL: DG–> MG
MGL: MG –> Glycerol

ATGL is rate-limiting

ATGL and HSL needs to be activated

MGL is constitutively activated

19
Q

What is CGI-58?

A

Interacts with perilipin
P-perilipin has a low affinity for CGI-58
Interacts and activates ATGL during lipolytic stimulation

20
Q

What does phosphorylated perilipin do?

A

Barrier to lipid droplets is removed
Allows ATGL to access TG in the core of lipid droplet
Facilitates increased lipolysis

21
Q

What activates ATGL

A

CGI-58

22
Q

What is Chanarin-Dorfman Syndrome? Caused by mutations in what?

A

Rare lipid storage diseases
Fats are stored abnormally in the body because they have impaired lipolysis
Fat accumulates in tissues (skin, liver, muscles, eyes, and ears) resulting scaly skins
Weak heart muscle
No cure but can treat symptoms with a low fat diet

Caused by mutations in CGI-58 so they cannot activate ATGL

23
Q

What does a mutation in CGI58 result in

A

Chanarin-Dorfman syndrome
Cannot activate ATGL
Impaired lipolysis

24
Q

Describe the carnitine shuttle

A

Shuttles FA from cytosol into mitochondria where they can be oxidized

Takes Acyl-CoA from the cytosol and attaches it to carnitine.

Acyl-carnitine is then shuttles to the matrix where it becomes acyl CoA against and undergoes B-oxidation

25
Q

What were to happen if you were carnitine deficient

A

Acyl CoA would not be able to cross the mitochondrial membrane

Easily fatigued
Weak muscles
Can lead to death from heart failure

26
Q

Which enzyme transports across which membrane

A

CPTI transports across the outer mitochondrial membrane
Translocase transports across the inner mitochondrial membrane
CPTII detaches Acyl from carnitine

27
Q

What is carnitine synthesized from?

A

Synthesized in the liver/kidney from lysine and methionine
Also in the diet

28
Q

What mutation results in carnitine deficiency? Effects? what is the treatment?

A

OCTN2 - defect in the carnitine transporter
Decreased carnitine transport resulting in decreased transport of FA to mitochdondria
Treatment: carnitine supplementation, avoid fasting, frequent feeding

29
Q

What do mutations in OCTN2 result in

A

OCTN2 is the transporter for carnitine
Mutation in OCTN2 results in decreased ability of tissues to take up carnitine
Imparied transport of fatty acids into mitochondria resulting in decreased fatty acid oxidation
leading to heart failure

BMIS 435 (17 decks)

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