Lipolysis Flashcards
What is lipolysis
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
What are lipases
break down ester bonds of triacylglycerol to release 3 FA
What are lipid droplets? What is the role of LD in adipocytes and structure?
Organelle that contains TG
TG storage in adipocytes
present in cytosol
Surface of phospholipids and proteins
Core of TG
T/F lipid droplet-associated proteins have specific functions
True
What is the most abundant lipid droplet protein
Perilipin
Function of perilipin
Forms a barrier around LDs
Prevents unwanted lipolysis
What is immunofluorescence microscopy
Visualize specific proteins in cells
allows you to see the location of a protein in a single cell
What happens to perilipin when lipolysis is activated
Perilipin undergoes a conformational change
Can access TG
Was the classic pathway of lipolysis correct? Why or why not
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
What is HSL
HSL is a DG lipase and is not the lipsae responsible for TG hydrolysis during lipolysis
What accumulates in HSL ko-mice
DG accumulated
All lipases have what motif?
GXSXG
(Serine is important for catalysis)
What was the enzyme that was found to be responsible for the first step of lipolysis?
Adipose Tissue Triacylglycerol Lipase (ATGL)
Where is ATGL present
Adipocytes
What happened in ATGL KO mice
TG lipase activity was reduced by 80%
Lipolysis was impaired
How is lipolysis measured
rate of fatty acid release into media
What is isoproterenol
A drug that stimulates lipolysis when incubated with adipose
Mimics epinephrine
What are the three lipases involved in lipolysis? Which enzyme is rate-limiting? Which enzyme needs to be activated?
ATGL: TG –> DG
HSL: DG–> MG
MGL: MG –> Glycerol
ATGL is rate-limiting
ATGL and HSL needs to be activated
MGL is constitutively activated
What is CGI-58?
Interacts with perilipin
P-perilipin has a low affinity for CGI-58
Interacts and activates ATGL during lipolytic stimulation
What does phosphorylated perilipin do?
Barrier to lipid droplets is removed
Allows ATGL to access TG in the core of lipid droplet
Facilitates increased lipolysis
What activates ATGL
CGI-58
What is Chanarin-Dorfman Syndrome? Caused by mutations in what?
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
What does a mutation in CGI58 result in
Chanarin-Dorfman syndrome
Cannot activate ATGL
Impaired lipolysis
Describe the carnitine shuttle
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
What were to happen if you were carnitine deficient
Acyl CoA would not be able to cross the mitochondrial membrane
Easily fatigued
Weak muscles
Can lead to death from heart failure
Which enzyme transports across which membrane
CPTI transports across the outer mitochondrial membrane
Translocase transports across the inner mitochondrial membrane
CPTII detaches Acyl from carnitine
What is carnitine synthesized from?
Synthesized in the liver/kidney from lysine and methionine
Also in the diet
What mutation results in carnitine deficiency? Effects? what is the treatment?
OCTN2 - defect in the carnitine transporter
Decreased carnitine transport resulting in decreased transport of FA to mitochdondria
Treatment: carnitine supplementation, avoid fasting, frequent feeding
What do mutations in OCTN2 result in
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
