Lipids 2 Flashcards
Breakdown, oxidation, synthesis and storage.
Describe the synthesis of free fatty acids, when in the fasted state.
When in the fasted state, the adipocyte triglyceride is broken down and released by lipolysis.
As insulin levels are low, glucagon (anti-hormone of glucose) levels are high and beta adrenergic receptors levels rise, due to neuronal stimulation of adipocytes.
B-adrenergic receptor is activated, and it recruits Adenylate cyclase, which produces cAMP.
cAMP binds to protein kinase A, activating it.
This leads to the phosphorylation of perilipin (which controls access to the lipid within the cell). This releases ABHD5 which binds to adipose triglyceride lipase.
Describe the synthesis of fatty acids.
The synthesis of fatty acids happens through a complex called fatty acid synthase.
Where does the synthesis of fatty acids take place.
The synthesis of fatty acids takes place in the liver, lactating mammary glands and adipose tissue.
What are the 3 ways we can derive fatty acids.
Synthesis
Diet
Stored lipid.
Define the “citrate shuttle”.
The citrate shuttle is used to allow the transfer of the acetyl part of acetyl CoA from the mitochondria to the cytosol.
Describe the synthesis of fatty acids.
Acetyl CoA combines with bicarbonate and passes through the Acetyl CoA Carboxylase enzyme (using ATP and producing ADP and Pi).
This produces Malonyl CoA.
Describe lipolysis.
Lipolysis is the breakdown of lipids - triacylglycerol to three fatty acids and a glycerol molecule - for energy.
It is regulated by a number of molecules: adenylate cyclase, cAMP, PKA, HSL, Perilipin, ABHD5, ATGL, MGL.
Describe the process of lipolysis.
In the fasted state, the insulin levels are low - glucagon levels rise, so does B-adrenergic receptor activity (low insulin - high epinephrine).
Both of these factors cause the activation of Adenylate Cyclase, this activation produces cAMP.
cAMP then binds to and activates PKA - PKA then phosphorylates both HSL (hormone-specific lipase), and Perilipin.
Once Perilipin is activated, it releases ABDH5.
An enzyme complex is then formed with ATGL (adipocyte triglyceride lipase) ABDH5 and HSL.
This enzyme complex then facilitates the consecutive cleaving of the acyl groups from triacylglycerol (one by one).
Triacylglycerol - to - diacylglycerol + 1 free FA.
Diacylglycerol - to - monoacylglycerol + 2 free FAs.
Monoacylglycerol - to - 3 FAs and glycerol.
State the two fates of the free FA’s within the body.
1) Oxidation (beta) / BURN
2) Triacylglycerol / STORE
Describe the B-oxidation of fatty acids.
B-oxidation takes place within the mitochondrial matrix, the “Fatty Acyl CoA” is transported into the mitochondria by the Carnitine shuttle.
Shorter fatty acids are oxidised in the MM.
Medium fatty acids are oxidised in the MM but through the Carnitine Shuttle.
Long chain fatty acids are too big for MM, so are oxidised in Peroxisomes.
Describe the mechanisms of the Carnitine Shuttle.
The Carnitine shuttle consists of 2 enzymes - CPTL 1 (rate-limiting enzyme) and CPTL 2.
In the cytosol, the fatty acids bind an acetyl coenzyme A to create - Fatty Acyl CoA.
Fatty Acyl CoA can cross through the outer mitochondrial membrane.
However, the inner mitochondrial membrane does not allow for the transfer of Fatty Acyl CoA, so a complex is formed with the Fatty Acyl CoA molecule + Carnitine.
The complex can move across the inner mitochondrial membrane, once within the mitochondrial matrix, carnitine is released as a product, and Fatty Acyl CoA remains.
Describe the process of B-oxidation of fatty acids.
Fatty Acyl CoA is within the mitochondrial matrix. The molecules passes through the
[Fatty Acyl CoA Dehydrogenase] enzyme.
This produces Acetyl CoA - can either enter TCA cycle (where is would then continue to ETC and produce ATP) or contribute to ketone bodies in the liver for storage of energy.
**The acyl molecule at the end of the B-oxidation cycle is 2 carbon atoms shorter than the last.
