In our body, lipid molecules like cholesterols, fatty acids, cholesterol ester, phospholipids etc are absorbed and transported into the blood in the form of chylomicrons. The outer layer of chylomicron is full of apolipoprotein and the inner layer is full of lipid materials.
Metabolism of fat:-
Fats are mainly oxidized by beta oxidation process. In this process, the beta carbon in the first reaction is oxidized and results in the removal of 2 carbon fragments from the intact fatty acid. After each beta oxidation cycle, the fatty acid becomes 2 carbon shorter.
Catabolism of fatty acids occur by both major as well as minor pathways. The major pathway include beta oxidation and minor pathway include alpha oxidation and omega oxidation.
It is the major pathway or process in which the oxidation of fatty acids takes place at the beta carbon atom; and results in removal of 2 carbon fragments in the form of acetyl-CoA.
Location of beta oxidation:- mitochondrial matrix of liver and other cells.
The three steps involved in the beta oxidation process are as follows-
- Activation of fatty acid to acyl-CoA: This reaction for the activation of fatty acid occurs in the cytosol and requires energy in the form of ATP. Activation of fatty acid is done by thiokinases or acyl-CoA synthetases. It occurs in two step and requires co-enzyme A and Mg ions.
2. Transportation of acyl-CoA to the mitochondria:- The inner mitochondrial membrane is impermeable to fatty acid. So this happens through the specialized carnitine transport system It occurs in 4 steps:
- Acyl group of acyl-CoA is transferred to carnitine through CAT-1 enzyme found in the outer surface of inner mitochondrial membrane.
- The acyl-carnitine is transported across the membrane to the mitochondrial matrix through a protein carrier.
- Acyl-carnitine is then converted to acyl-CoA through CAT-2 enzyme found in the inner surface of inner mitochondrial membrane
- The carnitine released moves back to the cytosol for reuse.
This system is described in the below given image
3. Beta oxidation of acyl-CoA:- This step involves four reactions
a. oxidation of FAD: The first step is the oxidation of fatty acyl-CoA by acyl-CoA dehydrogenase trans enoyl-CoA. The coenzyme for dehydrogenase enzyme is FAD which is then converted to FADH2.
b. Hydration:- The next step is hydration (that is addition of water) of double bond between C2 and C3 by enoyl-CoA hydratase enzyme to form beta hydroxy acyl-CoA.
c. Oxidation of NAD:- The beta hydroxy again undergoes oxidation and forms beta keto acyl-CoA. This reaction is catalyzed by beta-hydroxy acyl-CoA dehydrogenase.
d. Thiolysis (cleavage):- Lastly, the keto acyl-CoA is split at the beta carbon by thiolase enzyme which also involve another molecule of CoA-SH to form acetyl-CoA and a acyl-CoA which is shorter by 2 carbon atoms.
The formed acetyl-CoA is used in TCA cycle and generate 12 ATP.
Bioenergetics of Beta oxidation
Example: Palmitic acid which is 16 carbon atom long chain fatty acid
If palmitic acid undergoes beta oxidation, after the completion of the process it will generate:-
- 8 molecules of acetyl-CoA (which enters kreb’s cycle)
- 8*12 ATP = 96 ATP
- 7 molecules of FADH2
- 7*2 ATP = 14 ATP
- 7 molecules of NADH+H+
- 7*3 ATP = 21 ATP
- So total, 96+14+21=131 ATP. Total gain after the beta oxidation of 1 molecule of palmitic acid is 131 ATP.
- ATP molecules are utilized during the activation of palmitic acid, so the net gain is 129 ATP through beta oxidation.
Regulation of Beta oxidation
There are 2 types of regulation
- Enzymatic regulation:- CAT-1 is the principal enzyme as it catalyzes the rate limiting step of beta oxidation; which is formation of acyl carnitine. CAT-1 is allosterically inhibited by malonyl-CoA.
- Hormonal regulation: It has 2 conditions
- during well fed condition, the level of insulin increases which in turn increases the level of malonyl-CoA. and this inhibits the beta oxidation process
- during starvation, the level of glucagon increases, which decreases the level of malonyl-CoA and stimulates the beta oxidation.
Minor pathways of fatty acid catabolism
- Alpha oxidation:-
- In this process, removal of 1 carbon atom at a time from the fatty acid takes place. the removal of carbon is in the form of CO2.
- It is mainly involved in decarboxylase activity
- This process is used to convert even number of fatty acids into odd number of fatty acids in brain cells
- Alpha oxidation does not involve binding of fatty acids to co-enzyme A and thus does not release energy.
- Omega oxidation:-
- In this process, the oxidation starts from the end.
- It involves hydroxylation followed by oxidation of omega-carbon present as the methyl group at the other end.
- It mainly requires when the body need dicarboxylic fatty acid such as pimelic acid(a precursor for the biochemical synthesis of biotin).
- This reaction requires cytochrome P450, NADPH, O2 and the enzymes.
Multiple choice questions (MCQs)
1. In which form, the lipids are transported into the blood?
A. Chyme B. Apolipoproteins
C. Chylomicrons D. Micelles
2. The outer layer of chylomicrons is full of which substance?
A. Apolipoproteins B. Phospholipids
C. Cholesterols D. All of the above
3. Through which process, the catabolism of fat occurs?
A. Beta oxidation B. Omega oxidation
C. Alpha oxidation D. All of the above
4. Match the following-
a. Acyl-CoA dehydrogenase 1. ketoacyl-CoA to acetyl CoA
b. Hydratase 2. hydroxyacyl-CoA to ketoacyl-CoA
c. Beta-hydroxy acyl-CoA dehydrogenase 3. transenol to hydroxyacyl
d. Thiolase 4. acyl-CoA to trans enol
5. After each oxidation cycle, how many carbons are removed?
A. 2 B. 1
C. 3 D. 4
6. Where does beta oxidation takes place?
A. Mitochondria B. Cytosol
C. Ribosomes D. Nucleus
7. Which form of energy is required for activating the fatty acids?
8. Which of the following statement is NOT true?
A. Omega oxidation is process for anabolism of fatty acid
B. Alpha oxidation is used in brain cells
C. In omega oxidation, process starts from end
D. Alpha oxidation removes 1 carbon at a time
9. Which process transports the acyl-CoA to the mitochondria?
A. Simple diffusion
B. Carnitine transport
C. Passive transport
D. Active transport
10. Which is the first step of beta oxidation of acyl-CoA?
B. Oxidation of FAD
C. Oxidation of NAD
11. Which enzyme is termed as the principal enzyme for beta oxidation?
D. None of the above
12. Which hormone increases the level malonyl-CoA?
B. Growth hormone
13. Which activity is mainly performed by alpha oxidation process?
D. All of the above
14. During which condition, beta oxidation is stimulated?
A. Well fed condition
D. None of the above
15. What is the net gain through the beta oxidation of palmitic acid?
A. 131 ATP
B. 130 ATP
C. 129 ATP
D. 132 ATP
3. All of the above
4. a – 4 b – 3 c – 2 d – 1
8. Omega oxidation is process for anabolism of fatty acid
9. Carnitine transport
10. Oxidation of FAD
11. None of the above
15. 129 ATP
REFERENCE:- Pankaja Naik- Biochemistry; 4th edition; page no:- 212-216.