Lipid Metabolism Flashcards
Diet glucose and diet amino acids can turn into what and where
Acetyl-CoA in the liver
-here we can have De-Novo FA synthesis
These fatty acids are packaged generating VLDL and sent into circulation
Diet fatty acids are packaged into
chylomicrons in the intestinal epithelium and then stored as triglycerides in adipose tissue.
Fatty acids are transported in the blood as . . .
- Non-esterified FA with albumin (so they don’t precipitate).
- Triglyceride associated with apolipoproteins and cholesterol esters (lipoproteins)
Major lipoproteins include
Chylomicrons-made in intestinal epithelial cells
VLDL- made in liver(
LDL- delivers liver cholesterol to periphery
HDL- delivers periphery cholesterol to liver
Lipid digestion and chylomicrons
Lipases cut FA (triglycerides) to make DAG and Beta -monoacylglycerol (BMAG) – BMAG can be absorbed into the intestinal epithelium and is repackaged into triglycerides. Triglycerides then packaged into chylomicrons which go into lymphatic system which bypasses the hep portal vein and enters at the sub clavian. So. . . heart is one of the first to set lipids.
Excess carbs and proteins to FA
Lots of carbs and protein go to AcCOA —->FA—>Triglycerides —->VLDV——>Circulation
Pathway of FA synth
Acetyl CoAa –> Malonyl -CoA (via Acetyl-CoA carboxylase) Adds bicarb to Acetyl CoA
Malonyl -CoA - to Malonyl ACP (here they are packed into triglycerides and will stay till mobilization) Primarily in liver and adipose.
Malonyl-ACP to Fatty Acyl -ACP (cytosol)
Fatty Acyl CoA to Fatty Acid
ACC1
FA synthesis
ACC2
Regulates fatty acid oxidation (SkMuscle, liver, cardiac muscle)
Things to know about FA synthase
Dimer
Multiple enzymes
Synth 2 FA at same time
Transfers FA to diff domains sequentially.
Keeps moving domains.
Runs until it makes a 16 C
Primary product of FA Synthesis
Palmitate
Location of synthesis of unsaturated FA
ER
Regulation of ACC1
More AceCOA (more carbs)
Activated by citrate
Inhibited by fatty acyl-CoA (activated form of FA)
Activation/Inactivation of ACC regarding phosphorylation
P-inactive
P-active
Insulin activated PP2 which activates ACC
High insulin means low PKA
Inhibitors of ACC1
Activators of ACC1
FA-CoA(we have plenty)
PKA (puts a P on ACC)
Fasting (Fed state is desired)
Activators :
Citrate
PP2
High carb . low fat
Lipoprotein lipase and increasing FA concentration
Sits right on the border of adipose cells and hydrolyzes triglyceride right at the surface in order to increase the concentration of FA. FA move into adipose cells and are packaged into triglycerides.
Triglyceride synthesis
- Activate the FA by adding on a CoA group making Fatty acyl CoA. (Thiokinase)
- Take 2 Fa-CoA and add them to G3P to make a phosphorylated form of DAG called Phosphatidic acid. (Acyltransferase)
- Phosphatidic acid is then hydrolyzed to make DAG ( Phosphatase)
- DAG then gets a Fatty acyl Co-A added on to make triacyl glycerol ( Acyltranferase)
Occurs in Liver, Adipose, Intestine
G3P synthesis
Glycerol kinase (liver only )
DHAP- from glucose-DHAP can be make to make the Glycerol backbone.
Initiates lipolysis of triglycerides
Hormone sensitive lipase
PKA activated lipase
True
Phosphorylated form of triacylglycerol lipase (active form) is done so by PKA.
Glycerol must be release in to circulation why ?
So glycerol kinase can act on it
Carnitine shuttle
Carnitine acyl transferase 1 (CAT1) Takes fatty acyl-CoA and takes the Co-A group off and subs in a carnitine.
- O-acylcarnitine enters MM via acylcarnitine translocate
- Now O-acylcarnitine undergoes reverse RXN via CAT2 to regenerate L -carnitine.
16 C palmitate undergoes -rounds
7 rounds of b ox, this liberates 8 Ac-CoA and lots of NADH and FADH2
Cutting of Odd chain FA
undergoes B-ox until 5C long then 5C splits into 2C-acyly Co-A and 3 carbon propionyl Co-A
prop-CoA can’t undergo b-oxidation ,so it gets converted to succinyl-CoA
Enzyme required for b-ox of unsaturated FA
enoyl-CoA isomerase
Malonyl-CoA inhibits what?
CAT1
