Reactions of β- Oxidation and Calculation of Number of ATP Yield

Reactions of β- Oxidation

The way of β- Oxidation may not be same from the fatty acid with one sort of nature to that of other. The steps involved in the oxidation of fatty acid with odd chain may be slightly differed to that in the oxidation of fatty acids with even chain. And the steps involved in the oxidation of fatty acids containing saturated chain may be slightly differed from that of unsaturated chained fatty acids. We are going to briefly study these cases of β- Oxidation in fatty acids.

β- Oxidation Cycle of Saturated Fatty Acid (Even numbered)

As discussed in general steps β- Oxidation, the steps in this case also will remain same. Here as being more specific, we are taking the reference of only those fatty acids that contain the even numbered and saturated carbon chain. The oxidation of such fatty acids will be easier with compared to that of unsaturated and odd-numbered chain. Being the even numbered chain, it will facilitate for the easy oxidation of itself and removal of carbon fragments in the form of acetyl-CoA in a regular pattern. In β- Oxidation cycle, the oxidative removal of 2 carbon units in the form of Acetyl CoA occurs in the set of following reaction steps described below:

1) Oxidation:

In this step, the provided fatty acid is oxidized by the removal of hydrogen atoms from it. These lost H-atoms are utilized to reduce FAD to produce FADH₂. This reaction is called dehydrogenation reaction and is catalyzed by the enzyme, Acetyl CoA dehydrogenase. This results in the formation of carbon- carbon double bond between α (2) and β (3) carbon yielding a Trans-Δ²- enoyl- CoA. The symbol Δ² denotes the position of the double bond in the fatty acyl chain.

2) Hydration

In the further reaction, there is the occurrence of hydration of the double bond produced in reaction 2 during the first oxidation of the fatty acid. As a consequence, the β-carbon is hydroxylated because of which the double bond between α (2) and β (3) carbon is again saturated and the remaining chain of fatty-acyl-CoA is again ready for next oxidation and removal of another 2 carbon fragment in the form of acetyl-CoA. This reaction is catalyzed by the enzyme, enoyl-CoA hydratase that results in the formation of β-hydroxyacyl-CoA (3-hydroxyacyl-CoA).

3) Oxidation

In the next step (step 3), β-hydroxyacyl-CoA is oxidized to form β-ketoacyl-CoA. The enzyme, β-hydroxyacyl-CoA dehydrogenase catalyzes this reaction and NAD⁺ acts as an electron accepter and itself gets reduced into NADH.

4) Cleavage

This is the fourth and the last step of β- oxidation cycle in which an Acetyl-CoA is removed from β-ketoacyl-CoA by splitting off the carboxyl-terminal two-carbon fragments from the original fatty acid chain. The enzyme, acyl-CoA acetyltransferase catalyzes the reaction. Apart from acetyl-CoA, the other product is acyl-CoA, which is shortened by a two-carbon fragment. This two-carbon shorter fatty acyl-CoA again reenters the same kind of oxidation cycle. It is further oxidized by the same reaction. This process continues repeating until the total fatty acyl CoA chain is degraded to Acetyl-CoA. Acetyl CoA is the gateway molecule of TCA cycle. So the Acetyl CoA, produced during the β-oxidation of fatty acids then enters the TCA cycle and electron transport chain yielding 12 ATP molecules.

β- Oxidation of Odd-Chained Fatty Acids

Most of the naturally occurring lipids contain the fatty acids with even carbon chain. But many plants and marine organisms, among which fatty acids with long odd carbon chain are also common. The long-chained odd carbon fatty acids are also oxidized in the same pathway as the even numbered fatty acids, beginning at the carboxyl end of the fatty acid chain. The overall process remains same unless the last three carbon molecule, propionyl-CoA is obtained. Rest of the chain is reduced to propionyl-CoA by the liberation of Acetyl-CoA by the normal β-oxidation process as in the case of even-numbered fatty acids. But the process is now fluctuated due to the presence of last remaining product, propionyl-CoA

Fig:β- Oxidation Cycle of Saturated Fatty Acid (Even numbered)

Propionyl-CoA, rather going the further oxidation in the same cycle, gets converted into succinyl-CoA. This succinyl-CoA passes to the TCA cycle and yields 1 GTP, 1 FADH₂ and 1 NADH + H⁺, which in total produces 6 ATPs.

The process of oxidation of propionyl-CoA to succinyl-CoA involves the carboxylation of propionyl-CoA to D- Methyl malonyl-CoA and its conversion to succinyl-CoA. The process requires the conversion of D- Methyl malonyl-CoA to L- Methyl malonyl-CoA. This conversion is followed by the exchange of position by the substituents (-S-CoA) on the adjacent carbon atom as shown in the figure.

β- Oxidation of Unsaturated Fatty Acids

There are similar steps for the oxidation of unsaturated fatty acids too as compared to that of saturated fatty acids. However tow similar enzymes, Isomerase and reductase are required here in this case. The function of Isomerase is to convert the Cis-double bond, that occurs in naturally occurring fatty acids to Trans conformation and the function of Reductase is to bring the double bond to the correct position i.e. between α (2) and β (3) position.

Another difference here in this case with compared to that in saturated fatty acids is that there already exists double bond due to which the first oxidation producing FADH₂ is skipped off i.e. FADH₂ in the case of oxidation of unsaturated fatty acids is not produced per double bond.

Regulation of β-Oxidation

Regulation of β-Oxidation is observed and studied as primary and secondary signals.

1) Primary signals:- Effects on hormone-sensitive lipase.

Insulin turns off

Glucagon turns on

Epinephrine turns on

Phosphorylation turns on

2) Secondary signals:-

Malonyl CoA inhibits the Carnitine acyltransferase.

ATP calculation in β-Oxidation cycle:

Taking the reference of steric acid, an eighteen carbon saturated fatty acid:-

Activation step: - -2 ATP (ATP investment)

Oxidation step: -

8 FADH₂ * 2 ATP per FADH₂ 16 ATP

8 NADH * 3 ATP per NADH 24 ATP

9 Acetyl-CoA in TCA Cycle:-

9 * 1 GTP * 1 ATP per GTP 9 ATP

9 * 3 NADH * 3 ATP per NADH 81 ATP

9 * 1 FADH₂ * 2 ATP per FADH₂ 18 ATP

Total 146 ATP

Similarly, in the case of palmitic acid, a sixteen carbon saturated fatty acid, a total of 129 ATP is produced.

2 ATP molecules are considered to be invested in activation step as an ATP molecule is hydrolyzed to AMP and PPi, where two phosphoanhydride bonds are invested. This is economically equal to the break-down of one phosphoanhydide bond each from two ATPs to convert to two ADPs.