M3: Fatty Acid Breakdown L19

Question 1

Which of the following is(are) correct right after a meal?
Select ALL that apply.
A. Liver will breakdown fatty acids to generate ATP
B. Adipose tissue will store fatty acids from the diet in lipid droplets
C. Muscle will breakdown fatty acids to regenerate glucose
D. Liver will uptake fatty acids from chylomicron remnants

Answer 1

B & D

Question 2

Which of the following metabolic circumstances require(s) breaking down fatty acids to generate energy? Select ALL that apply
A. During prolonged exercise
B. After a fat-rich meal
C. After a glucose-rich meal
D. After a fructose-containing meal
E. Exhausted glycogen stores in muscle

Answer 2

A & E

Question 3

Where do fatty acids come from?

Answer 3

1. Uptake from circulation:
   A) from the diet: Lipids from diet incorporated into chylomicrons (lipoproteins) which circulate and meet the lipoprotein lipase on the surface of endothelial cells just next to adipose tissue and/or muscle cells which lypolises the tryglicerides to release fatty acids.
   B) From the liver: VLDL synthesized by liver (similar to chilomicrons) meets LPL to hydrolyzes triglycerides to generate the fatty acids.
2. Lipolysis
   Lipolysis of lipid vesicles that are inside the cell: Lipid droplets that have accumulated lipids under the form of triacylglycerol (triglycerides). Under hormonal stress (adrenaline stimulus) there will be phosphorylation of perilipin, and HSL which degrades the TAGs and regenerates fatty acids. Those Free fatty acids will circulate in blood bound by albumin. The albumin will deliver the free fatty acids to cells that need energy such as muscle.
3. Phospholipases A1 & A2 (Lang’s cycle)
   Reorganization of phospholipids

Question 4

How do long chain fatty acids get transported into the mitochondrial matrix?

Answer 4

Step 1: activation by CoA via Acyl-CoA Synthetase

• Activates the FA (high energy) (pyrophosphatase drives the reaction)
• Keeps FA inside of cells
• Generates a gradient that allow more FA in
• After further reactions you get Acyl-CoA

Step 2: coupling of Acyl-CoA & Carnitine via Carnitine Palmitoyl Transferase I (CPT I)

• Rate-limiting step
• Fatty Acylcarnitine is brought to intermembrane space by CPT1

Step 3: transit toward the mitochondrial matrix via Carnitine:acylcarnitine translocase (Antiporter that takes up acylcarnitine into mitochondrial matrix and takes carnitine out of matrix and puts it into inter membrane space of mitochondria)

Step 4: FA release into the matrix via
Carnitine Palmitoyl Transferase II (CPT II)
-Regenerates Acyl-CoA inside the matrix (CoA prevents going back to cytosol)
-Carnitine recycles back to the cytosol

Question 5

How is CPT1 regulated?

Answer 5

CPT I = Rate-limiting step of FA breakdown

• Inhibited by malonyl-CoA (a fatty acid) in the cytosol
• High [malonyl-CoA]cytosol means you’re in a High energy state and you’re doing Biosynthesis of FA, therefore you Must stop breakdown.

Question 6

Study B-oxidation from the PPT for saturated, unsaturates, polyunsaturated, odd-chain, and branched chain FA.

Answer 6

M3, L19, Slides 16-26

Question 7

What are the 3 ketone bodies?

Answer 7

1. Acetoacetate
2. Acetone
3. B-Hydroxybutyrate

Question 8

How are ketone bodies produced?

Answer 8

After breakdown of fatty acids, there is a bunch of Acetyl-CoA in the liver, but there’s not enough glucose in the blood (during fasting or starvation) and you need to deliver Acetyl-CoA to the brain. So the Acetyl-CoA will be converted to smt soluble so it can get through the membrane and be transported through the blood to the brain.

1. Acetyl-CoA loses a CoA and turns into acetate so that acetyl can get out of the cell
2. Acetate is combined with another acetyl-CoA to make acetoacetyl-coA
3. acetoacetyl-coA is converted to HMG-COA via HMG-CoA synthase
4. HMG-CoA is converted to the 3 ketone bodies Acetoacetate, Acetone, B-Hydroxybutyrate.

Question 9

Where and when are ketone bodies made?

Answer 9

• Primarily in liver
• During fasting or starvation (low carbohydrate intake)
• Oxaloacetate is depleted bc of gluconeogenesis, CAC stops
• Problem = Acetyl-CoA doesn’t transfer between tissues
• Ketone bodies serve as a “shuttle” for acetyl-CoA between tissues
• Reversal of the thiolase reaction using acetyl-CoA as substrate
• Heart and brain use ketone bodies to regenerate acetyl-CoA

Question 10

What happens to acetone?

Answer 10

It is expired by the lungs and wasted in the breath. because it is volatile.