Fatty Acid Catabolism

What are the stages where triglycerides are cleaved to generate fatty acid and glycerol?

In fatty acid (lipid) oxidation, triglycerides are cleaved into fatty acids and glycerol during the process called lipolysis. This occurs in three enzymatic stages:

Stages of Triglyceride Breakdown (Lipolysis)

Triglyceride → Diglyceride + Fatty Acid

Enzyme: Adipose triglyceride lipase (ATGL)

Diglyceride → Monoglyceride + Fatty Acid

Enzyme: Hormone-sensitive lipase (HSL)

Monoglyceride → Glycerol + Fatty Acid

Enzyme: Monoglyceride lipase (MGL)

Free fatty acids in the bloodstream are:

b. carried by the protein serum albumin

What is the role of bile acids in lipid metabolism?

Bile acids are essential for the digestion and absorption of dietary lipids in the small intestine. They:

Emulsify fats, breaking large fat globules into small droplets

Increase the surface area for pancreatic lipase action

Form mixed micelles that solubilize and transport:

fatty acids

monoglycerides

cholesterol

fat-soluble vitamins (A, D, E, K)

Enable efficient absorption of lipids by intestinal mucosal cells

In short, bile acids make lipids digestible and absorbable in an aqueous intestinal environment.

What is the difference between Chylomicron and different density lipoproteins (LDL, HDL, IDL, VLDL)

Chylomicrons transport dietary triglycerides from the intestine to tissues.

VLDL transports endogenous triglycerides from the liver to tissues

IDL is an intermediate formed from VLDL metabolism.

LDL transports cholesterol to peripheral tissues ("bad cholesterol").

HDL transports cholesterol from tissues back to the liver ("good cholesterol").

Key difference: Chylomicrons carry dietary lipids, while LDL, HDL, IDL, and VLDL carry lipids synthesized in the liver.

4.Describe an extremely important role played by HDL in body.

It's very hungry for hydrophobic molecules so as it circulates, it absorbs cholesterols and other fatty deposits from capillaries and cleans them

5.How is the stored lipid in adipose tissue used for energy generation in muscle?

If one is not eating fat, does that mean no fat is being catabolized? If you don't eat fat for three days what will happen? The third stage is the hormone dependent triacylglycerol lipase; if body needs fat, or if there's excess of fat and the body needs it, then from the bank from the storage, the hormone dependent lipases get activated. So in the adipocytes fat is catabolized and fatty acids are absorbed into the blood and immediately loaded onto to albumin and then they can go to the muscles for uses.

6.What is the difference in the reactions of Acyl-CoA synthase and Carnitine acyl transferase II?

In the cytosol, you generate fatty acyl-CoA by fatty acyl-CoA synthetase, which uses ATP

- In the mitochondria, you generate fatty acyl-CoA by carnitine acyl transferase II.

- SO what is the difference?

- In the cytosol, the synthetase uses energy, ATP, to activate the fatty acid and then add CoA onto to the to make fatty acyl-CoA

- This is a highly reactive molecule, a high-energy molecule

- When CoA comes out it is replaced by carnitine

- There is no high energy molecule required here, no ATP required

- Carnitine is also high-energy molecule, which comes inside and then this molecule is converted to fatty acyl-CoA because CoA can replace carnitine and make fatty acyl CoA without using ATP why? Because carnitine is a high-energy compound to start with. And why is that a high-energy molecule? Because it was made by another high-energy molecule, fatty acyl-CoA.

- ATP invested in the first step has given the energy to make high-energy molecule or activate the fatty acid and the energy remains all the way.

- That energy remains so that in the mitochondria you don't need ATP

7.List the enzymes involved in oxidative steps of fatty acid catabolism.

Fatty acyl-CoA Dehydrogenase

o The you unsaturated that bond and make enoyl-CoA and then that one is hydrated and you make B-hydroxy enoyl-CoA.

- B-hydroxy enoyl-CoA Dehydrogenase

o Uses NAD+ as cofactor and the very first enzyme uses FAD as co factor

- Don't include fatty acyl CoA synthetase because that is the activation step

- These are the two oxidative steps in the beta-oxidation but after beta-oxidation, you get acetyl-CoA, which is further completely oxidized to CO2 by CAC cycle. The oxidative steps in CAC cycle are isocitrate DH, alpha-ketoglutarate DH, Succinyl-CoA DH and malate DH.

8. How many molecules of FADH2 and NADH are produced from a 16 carbon chain fatty acid (palmitic acid).

8 and 24 which makes a total of 32

- During beta-oxidation, how many NADH do we make?

o 7 NADH and 7 FADH2

- Now CAC cycle

o 8 acetyl-CoA will be produced so the cycle will run 8 times

o So 8x3 à 24 NADH will be produced

o 8 FADH2 will be produced after 8 cycles

- 8+24 à32 in the CAC cycle

- 32+ 14 (b-oxidation) à46 total

- Out of which 15 will be FADH2 and 24 NADH (actually 31)

9. How many water molecules can be produced from oxidative catabolism of one molecule of palmitic acid.

46 molecules of reduced moiety are produced

- Each one of them makes one mole of water

- Each reducing moiety donates two electrons which is sufficient to make one mole of water

- So 46 moles of water in total

- How ever there is a consumption of water as well

- One water molecule is consumed per b-oxidation cycle so 7 will be consumed over there and during CAC cycle 2 are consumed per cycle so for 8 cycles, 16 moles of water

- 16+7= 23 moles of water are consumed

- 46 produced

- 23 moles water = net gain

10. Which enzyme in lipid catabolism requires vitamin B12 as cofactor?

MMM

- Methylmalonyl mutase

11. What are peroxisomes?

- They are the membrane bound structures in the cell where b-oxidation of long chain fatty acids occurs and in this organelle, the first enzyme of the b-oxidation is not bound to mitochondria so instead of transferring electrons from

FADH2 to the complex 2 and Co-Q10, in peroxisome, electrons are transferred directly to oxygen generating superoxide and then peroxide and that's why they're called peroxisomes.

12. Under what circumstances ketone bodies are produced?

Starvation or diabetic, when glucose is low

13.Name the enzyme of b-oxidation pathway, which is directly linked to mitochondrial ETC

- Fatty acyl-CoA DH

14.What is the name of the product remaining at end of the last cycle of b-oxidation of an odd-chain fatty acid?

Propionyl-CoA and then it convert that to succinate, we have to go through crazy steps

15.Dr Pandey weighs 65 Kg out of which 10 kg is due to fat deposit. He went for a hunger strike. How long he can survive without water and food.

a. Assume that: All 10 kg weight of fat store is Palmitic acid (16 carbon chain fatty acid).

Molecular weight of Palmitic acid = 243

Minimum water requirement per day for a person like him is 1.5 kg or Liter.

Moles of palmitic acid=24310,000​≈41.15 mol

1 mol palmitate→16 mol H₂O 41.15×16=658.4 mol H₂O41.15 \times 16 = 658.4 \text{ mol H₂O}41.15×16=658.4 mol H₂O

658.4×18=11,851 g≈11.85 L water

Survival days=1.511.85​≈7.9 days

b. If he was rescued just before falling unconscious due to dehydration. How will he look? What is the most important care that needs to be taken other than water infusion.

You will look terrible

- Most important care other then water infusion is glucose because the brain is dependent on glucose

6. The role of hormone-sensitive triacylglycerol lipase is to:

hydrolyze triacylglycerols stored in adipose tissue.

10. How do insulin and Glucagon regulate Fat metabolism?

nsulin (fed state)

Stimulates fatty acid and triglyceride synthesis in liver and adipose tissue

Activates lipoprotein lipase (LPL) → increases uptake of fatty acids into adipose tissue

Inhibits hormone-sensitive lipase (HSL) → decreases lipolysis

Promotes storage of fat as triacylglycerols

Glucagon (fasting state)

Stimulates lipolysis in adipose tissue by activating HSL

Increases release of free fatty acids into blood

Promotes β-oxidation of fatty acids in liver and muscle

Decreases fatty acid and triglyceride synthesis

In summary:

Insulin → fat storage

Glucagon → fat breakdown and utilization

Name the enzyme of -oxidation pathway, which is directly linked to mitochondrial ETC.

Acyl-CoA dehydrogenase generates FADH₂ during the first step of β-oxidation. The electrons from FADH₂ are transferred to the ETC via electron-transferring flavoprotein (ETF) and then to ubiquinone (CoQ), directly linking β-oxidation to the mitochondrial ETC.

The carbon atoms from a fatty acid with an odd number of carbons will enter the citric acid cycle as acetyl-CoA and

succinyl-CoA.

What is the name of the product remaining at end of the last cycle of B-oxidation of an odd-chain fatty acid?

β-oxidation cleaves fatty acids 2 carbons at a time as acetyl-CoA.

For odd-chain fatty acids, the last cycle leaves a 3-carbon fragment, which is propionyl-CoA.

Propionyl-CoA is then converted to succinyl-CoA, which enters the TCA cycle.

A 65 year old lady was found is a delirious and confused state sitting on a bench, and falling unconscious. Her breath has a strange smell similar to alcohol. People thought she was drunk. What would be your guess and action toward helping this lady?

Diabetic ketoacidosis (DKA) or Hyperosmolar Hyperglycemic State (HHS)

DKA occurs typically in type 1 or insulin-dependent type 2 diabetes, often triggered by infection, illness, or missed insulin.

"Alcohol-like" fruity breath is due to acetone, a ketone produced from fat metabolism when glucose is not available.

Elderly patients may present atypically (delirium, confusion) rather than classic symptoms (polyuria, polydipsia).

Start supportive care:

IV fluids for dehydration

Correct electrolyte imbalances

Administer insulin under hospital supervision if DKA is confirmed

Plasma analysis of a healthy person (without any genetic defect) who is 40 year old, weighing 80 kg, indicated that concentration of VLDL and LDL were very high, and HDL was very low. Answer the followings a. What could be the possible reasons for these results?

Dietary factors

High intake of saturated fats and trans fats → increases VLDL and LDL

Low intake of healthy fats (omega-3, monounsaturated fats) → reduces HDL

Lifestyle factors

Sedentary lifestyle → lowers HDL and impairs clearance of VLDL/LDL

Obesity or overweight → associated with high triglycerides and LDL

Is this person at risk of getting cardiovascular problem? Explain how.

High LDL (Low-Density Lipoprotein)

LDL carries cholesterol from the liver to peripheral tissues.

Excess LDL → cholesterol deposits in arterial walls → formation of atherosclerotic plaques.

Plaque buildup → narrowing of arteries (atherosclerosis) → heart attacks and strokes.

High VLDL (Very-Low-Density Lipoprotein)

VLDL carries triglycerides in the blood.

Excess VLDL → increases circulating triglycerides and small dense LDL, which is highly atherogenic.

Can promote inflammation and endothelial dysfunction in blood vessels.

Low HDL (High-Density Lipoprotein)

HDL is protective; it removes cholesterol from tissues and plaques and returns it to the liver (reverse cholesterol transport).

Low HDL → less cholesterol clearance → accelerates plaque formation.

hat would you recommend him to do to bring the LDL and HDLconcentrations normal?

Dietary changes, limiting butter, fried foods, red meat, increasing unsat fats,

physical activity