Lipid Metabolism

Question 1

Diet glucose and diet amino acids can turn into what and where

Answer 1

Acetyl-CoA in the liver

-here we can have De-Novo FA synthesis

These fatty acids are packaged generating VLDL and sent into circulation

Question 2

Diet fatty acids are packaged into

Answer 2

chylomicrons in the intestinal epithelium and then stored as triglycerides in adipose tissue.

Question 3

Fatty acids are transported in the blood as . . .

Answer 3

1. Non-esterified FA with albumin (so they don’t precipitate).
2. Triglyceride associated with apolipoproteins and cholesterol esters (lipoproteins)

Question 4

Major lipoproteins include

Answer 4

Chylomicrons-made in intestinal epithelial cells

VLDL- made in liver(

LDL- delivers liver cholesterol to periphery

HDL- delivers periphery cholesterol to liver

Question 5

Lipid digestion and chylomicrons

Answer 5

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.

Question 6

Excess carbs and proteins to FA

Answer 6

Lots of carbs and protein go to AcCOA —->FA—>Triglycerides —->VLDV——>Circulation

Question 7

Pathway of FA synth

Answer 7

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

Question 8

ACC1

Answer 8

FA synthesis

Question 9

ACC2

Answer 9

Regulates fatty acid oxidation (SkMuscle, liver, cardiac muscle)

Question 10

Things to know about FA synthase

Answer 10

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

Question 11

Primary product of FA Synthesis

Answer 11

Palmitate

Question 12

Location of synthesis of unsaturated FA

Answer 12

ER

Question 13

Regulation of ACC1

Answer 13

More AceCOA (more carbs)

Activated by citrate

Inhibited by fatty acyl-CoA (activated form of FA)

Question 14

Activation/Inactivation of ACC regarding phosphorylation

Answer 14

P-inactive
P-active

Insulin activated PP2 which activates ACC

High insulin means low PKA

Question 15

Inhibitors of ACC1

Activators of ACC1

Answer 15

FA-CoA(we have plenty)
PKA (puts a P on ACC)
Fasting (Fed state is desired)

Activators :

Citrate
PP2
High carb . low fat

Question 16

Lipoprotein lipase and increasing FA concentration

Answer 16

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.

Question 17

Triglyceride synthesis

Answer 17

1. Activate the FA by adding on a CoA group making Fatty acyl CoA. (Thiokinase)
2. Take 2 Fa-CoA and add them to G3P to make a phosphorylated form of DAG called Phosphatidic acid. (Acyltransferase)
3. Phosphatidic acid is then hydrolyzed to make DAG ( Phosphatase)
4. DAG then gets a Fatty acyl Co-A added on to make triacyl glycerol ( Acyltranferase)

Occurs in Liver, Adipose, Intestine

Question 18

G3P synthesis

Answer 18

Glycerol kinase (liver only )

DHAP- from glucose-DHAP can be make to make the Glycerol backbone.

Question 19

Initiates lipolysis of triglycerides

Answer 19

Hormone sensitive lipase

Question 20

PKA activated lipase

Answer 20

True

Phosphorylated form of triacylglycerol lipase (active form) is done so by PKA.

Question 21

Glycerol must be release in to circulation why ?

Answer 21

So glycerol kinase can act on it

Question 22

Carnitine shuttle

Answer 22

Carnitine acyl transferase 1 (CAT1) Takes fatty acyl-CoA and takes the Co-A group off and subs in a carnitine.

2. O-acylcarnitine enters MM via acylcarnitine translocate
3. Now O-acylcarnitine undergoes reverse RXN via CAT2 to regenerate L -carnitine.

Question 23

16 C palmitate undergoes -rounds

Answer 23

7 rounds of b ox, this liberates 8 Ac-CoA and lots of NADH and FADH2

Question 24

Cutting of Odd chain FA

Answer 24

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

Question 25

Enzyme required for b-ox of unsaturated FA

Answer 25

enoyl-CoA isomerase

Question 26

Malonyl-CoA inhibits what?

Answer 26

CAT1