Lipid Metabolism Flashcards
What kind of synthesis uses acetyl-coA to build up fatty acids?
De novo fatty acid synthesis
Where does fatty acid synthesis occur?
in the cytoplasm while acetyl-coA is in the mitochondria
How is Acetyl-coA shuttled out of the mitochondria?
through citrate
Fatty acid synthesis: starts with what, which adds... where does it occur? What molecule does it use? hows it regulated?
Starts with acetyl-coA that adds 2C units to a growing fatty acid chain. Happens in liver and adipose. Uses NADPH. Regulated by acteyl-coA carboxylase.
What is fatty acid synthesis regulated by and how does it work?
How is it activated?
How is it deactivated?
Regulated by acetyl-CoA carboxylase.
Deactivated by phosphorylation by AMP activated kinase or glucagon signaling (low energy situation) or epinephrine signaling (high energy mobility situation).
Activated by high (citrate) and by dephosphorylation by insulin signaling (high energy situation)
How are triglycerides synthesized and why?
Where does glycerol come from and what is it reduced to?
fatty acids > triglycerides for storage. Glycerol comes from glycolysis dehidroxyacetone phosphate which is reduced to glycerol-3-phosphate. 3 fatty acids added in a stepwise fashion to position 1, 2, then 3.
If the process of triglyceride synthesis stopped after adding position two, what would happen?
Diaglycerol phosphate would be produced and can be used for membrane lipid synthesis.
where does triglyceride synthesis occur? What are they stored in and how are they transported out to the rest of the body, as what compound?
happens in liver and adipose. stored in adipose and in liver it is transported ot the rest of the body by very low density lipoprotein (VLDL)
Lipolysis step 0a
What is important about this?
How is it regulated and what is it called?
hormone sensitive lipase/monoacyglycerol lipase - main control point, regulated by insulin and epinephrine.
Lipolysis step 0b
Name?
Wheres it occur?
What cant cross mitochondrial membrane and how do we get it into mitochondria?
fatty acyl CoA synthetase
activation reactions happen in the cytosol but further happen in mitochondria.
Fatty acyl CoA cant cross mitochondria, we use the Carnitine shuttle.
How does the carnitine shuttle work?
take CoA and put it on a carnitine which is able to go through translocase (pulls fatty acid into mitochondria). Translocase shuttles fatty acids in and free carnitines back out so It can grab another fatty acid and bring it in.
Lipolysis step 1Whats it called?
What occurs here?
Where is fatty acyl-coA located?
Acyl-coA DehydrogenaseBeta oxidation - need to oxidize the molecule twice so we use FAD, a double bond type of oxidation. In mitochondria
Lipolysis step 2
What is it called?
What happens when we add water?
Enoyl-coA HydrataseWhen we add water, We have oxidized the carbon so we get a reduced molecule of FADH2.
lipolysis step 3
3-hydroxyacyl-coA dehydrogenase
lipolysis step 4
Products go where?
Thiolase
Back to step one, to TCA cycle, and to ketone bodies
Lipolysis/Lipogenesis control
What is the function of Citrate?
Feed forward regulation of ACC - high energy
Goes towards Lipogenesis
Lipolysis/Lipogenesis control
What is the function of AMP?
What is ACC?
Activates AMP - activated protein Kinase phosphorylation activates HSL, inhibits ACC, low energy
Goes towards Lipolysis
Lipolysis/Lipogenesis control
What is the function of Insulin?
Activates protein phosphatase 2A
Dephosphorylation inhibits HSL, activates ACC
Goes towards lipogenesis
Lipolysis/Lipogenesis control
Function of Epinephrine?
Activates Protein Kinase A, phosphorylation activates HSL, inhibits ACC
Goes towards Lipolysis
Lipolysis/Lipogenesis control function of Glucagon?
Activates protein kinase A
phosphorylation activates HSL, inhibits ACC
Goes towards Lipolysis
Lipolysis/Lipogenesis control
Function of Malonyl-coA
What does it prevent?
Feed forward regulation of ACC (lipogenesis) blocks CPT1, prevents both sides from being active at the same time
What is the problem we will see if all we have is Acetyl-CoA if TCA cycle doesn’t run fast enough?
Using up free CoA to get Acetyl CoA so every time we complete one of these steps we get a free co A that gets added to get acetyl Co A. The TCA cycle is what gets out free CoA back. If we don’t have oxygen, TCA cycle will be messed up. CoA is also used in lipid synthesis.
We need to have sufficient oxygen and glucose.
Acetyl-CoA oxidation requires glucose
If we have low glucose, what happens to Acetyl-CoA?
Run out of glycogen > start gluconeogenesis (oxaloacetate drops bc gluconeogenesis doesnt replish it, TCA does), wont deplete it much bc we have gluconeogenic AA so we will use oxaloacetate but also produce it so the TCA cycle can run, can still get free coA back
What happens if we have very low glucose level?
run out of gluconeogenic substrates so we will shift to gluconeogenesis, we run out of oxaloacetate and the TCA cycle stops so we no longer get free coenzyme A back.
