Question

Calculate the energy yield from the oxidation of palmitoyl CoA. How do you account for the different energy yields between palmitoyl CoA, palmitic acid, and palmitoleic acid?

Answer 1

The total oxidation of a fatty acid comprehends different processes:

1. – The activation of the fatty acid

2. – Beta-Oxidation

3. – Krebs Cycle.

For being metabolized, a fatty acid should experiment activation:

Fatty acid + CoA + ATP ------> Acyl CoA + AMP + 2(P)

The activation of the fatty acid requires 1 molecule of ATP, but since two energy rich bonds are hydrolyzed (the ATP is hydrolyzed to AMP and 2 (P) ) for energetic balance purposes it is considered that 2 ATP have been consumed in this activation process)

The formed acyl CoA will experiment different oxidation reactions. These reactions occur in the Beta-carbon. That is why the process is called Beta-oxidation.

In Beta-oxidation (a mitochondrial process) the acyl CoA is totally oxidized to Acetyl groups in form of Acetyl CoA units.

Since the Acetyl group of the acetyl coA is formed by two carbons, we should divide the number of carbons in the acyl group between two.

Miristic acid (14 carbons): 14 carbons /2 = 7 Acetyl CoA

Palmitic acid (16 carbons): 16 carbons/2 = 8 Acetyl CoA

In one pass through the fatty acid oxidation sequence, one molecule of acetyl-CoA, two pairs of electrons, and four H⁺ ions are removed from the long-chain fatty acyl-CoA, to shorten it by two carbon atoms.

The equation for one pass, beginning with the coenzyme A ester of our example, palmitate, is

Palmitoyl-CoA + CoA + FAD + NAD⁺ + H₂O --------> myristoyl-CoA + acetyl-CoA + FADH₂ + NADH + H⁺   

Following removal of one acetyl-CoA unit from palmitoyl-CoA, the coenzyme A thioester of the shortened fatty acid remains, in this case the 14-carbon myristate.

The myristoyl-CoA can now enter the ?-oxidation sequence and go through another set of four reactions, exactly analogous to the first, to yield a second molecule of acetyl-CoA and lauroylCoA, the coenzyme A thioester of the 12-carbon laurate.

Altogether, seven passes through the ?-oxidation sequence are required to oxidize one molecule of palmitoyl-CoA to eight molecules of acetyl-CoA.

The overall equation is

Palmitoyl-CoA + 7CoA + 7FAD + 7NAD⁺ + 7H₂O --------> 8 acetyl-CoA + 7FADH₂ + 7NADH + 7H⁺   

Each molecule of FADH₂ formed during oxidation of the fatty acid donates a pair of electrons to ETFP of the respiratory chain, two molecules of ATP are generated during the ensuing transfer of the electron pair to O₂ and the coupled oxidative phosphorylations.

Similarly, each molecule of NADH formed delivers a pair of electrons to the mitochondrial NADH dehydrogenase; the subsequent transfer of each pair of electrons to O₂ results in formation of three molecules of ATP.

Thus five molecules of ATP are formed for each two-carbon unit removed in one pass through the sequence as it occurs in animal tissues, such as the liver or heart.

Note that water is also produced in this process. Condensation of ADP and Pi releases one H₂O for each ATP formed, and transfer of electrons from NADH or FADH₂ to O₂ yields one H₂O per electron pair. R,eduction of O₂ by NADH also consumes one H⁺ per NADH:

NADH + H⁺ + 2O₂ -------> NAD⁺ + H₂O.

In hibernating animals, fatty acid oxidation provides metabolic energy, heat, and water-all essential for survival of an animal that neither eats nor drinks for long periods.

The overall equation for the oxidation of palmitoyl-CoA to eight molecules of acetyl-CoA, including the electron transfers and oxidative phosphorylation, is

Palmitoyl-CoA + 7CoA + 7O₂ + 35Pi + 35ADP -------> 8 acetyl-CoA + 35ATP + 42H₂O

Acetyl-CoA Can Be Further Oxidized via the Citric Acid Cycle

The acetyl-CoA produced from the oxidation of fatty acids can be oxidized to CO₂ and H₂O by the citric acid cycle.

The following equation represents the balance sheet for the second stage in the oxidation of our example, palmitoyl-CoA, together with the coupled phosphorylations of the third stage:

8 Acetyl-CoA + 16O₂ + 96P_i + 96ADP -----> 8CoA + 96ATP + 104H₂O + 16CO₂

Combining Equations 16-4 and 16-5, we obtain the overall equation for the complete oxidation of palmitoyl-CoA to carbon dioxide and water:

Palmitoyl-CoA + 23O₂ + 131Pi + 13lADP ----> CoA + 13lATP + l6CO₂ + 146H₂O   

Because the activation of palmitate to palmitoyl-CoA consumes two ATP equivalents, the net gain per molecule of palmitate is 129 ATP.

The yields of NADH, FADH2, and ATP in the successive steps of fatty acid oxidation.

The standard free-energy change for the oxidation of palmitate to CO₂ + H₂O is about 9,800 kJ/ mol.

Under standard conditions, 30.5 × 129 = 3,940 kJ/mol is recovered as the phosphate bond energy of ATP.

However, when the free-energy changes are calculated from actual concentrations of reactants and products under intracellular conditions, the free-energy recovery is over 80%; the energy conservation is remarkably efficient.