Lipid Metabolism

Glycolysis &
Citric Acid Cycle
Protein Metabolism  Elmhurst College
Fatty Acid Spiral Reactions Acetyl CoA Fates Energy Summary  Chemistry Department
Overview, Summary Lipids Diabetes Reveiw Metabolism  Virtual ChemBook


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Overview of Fatty Acid Oxidation Reactions

Overview of Fatty Acid Beta Oxidation:

The major reaction to produce energy using lipids is in the fatty acid spiral. The beta oxidation of fatty acids occurs by the removal of two carbons at a time as acetyl CoA in a spiral type reaction. These reactions occur in the mitochondria and thus are closely associated with the electron transport chain to produce energy in the form of ATP. In addition, the acetyl CoA which is produced is feed mostly into the citric acid cycle.

The overall reaction is:

fatty acid CoA + NAD+ + FAD ---> acetyl CoA + NADH + H+ + FADH2

Link to: Fatty Acid Spiral (move cursor over arrows)
Jim Hardy, Professor of Chemistry, The University of Akron.

Link to animation of complete fatty acid oxidation - Brooks-Cole


 

Initiating Step:

For this example, the 16 carbon palmitic acid is being used.

The initial event in the utilization of fat as an energy source is the hydrolysis of the triglyceride by a lipase in the adipose tissue cell. Hormones such as epinephrine, norepinephrine, glucagon, and adrenocorticotrophic hormones, stimulate the adenyl cyclase in adipose cells. The sequence of reactions is similar to that already described for glycogenolysis in prior page. Ultimately, lipase is activated by a phosphorylation reaction.

Before fatty acids can be oxidized, they must first undergo an initiating or priming step. Fatty acids in the cytoplasm must cross the mitachondria membrane before the oxidations begin. Simple fatty acids are unable to cross this membrane unassisted. The overall initiating step is the reaction of the fatty acid with coenzyme A in a thioester formation. This reaction requires energy and is therefore coupled with the hydrolysis of ATP to AMP. The activated long chain fatty acid is carried across the mitochondria membrane by an organic compound called carnitine.

CoA and Palmitic Acid - Chime in new window

CoA and Palmityl CoA- Chime in new window

Fatty Acid Spiral:

The fatty acid-CoA molecule is degraded into acetyl CoA molecules by a recurring cyclic sequence of four reactions. The end product of each cycle is the fatty acid shortened by 2 carbons and acetyl CoA.

The series of reactions is also known as the beta-oxidation pathway because the major reaction site is the beta-carbon or #3 carbon from the thioester carbon. The complete reaction sequence for one fatty acid cycle is given as follows.

Actually, the reactions in the fatty acid cycle closely resemble the last three steps of the citric acid cycle.

Step 1: Oxidation (Dehydrogenation)

The coenzyme FAD, which is directly connected to the electron transport chain is involved with this reaction. Again it is somewhat unusual for hydrogens to be removed from an alkane hydrocarbon chain.

The hydrogens on the #2 and # 3 carbons are removed to form a trans double bond (alkene) type compound. The FAD is converted to
FADH2 and carries the two hydrogens and two electrons in the electron transport chain. Because this is the second enzyme complex, the net yield of ATP is two.

Palmityl-2-ene CoA- Chime in new window

Link to Chime: Acyl-CoA Dehydrogenase - Department of Biochemistry,The University of Arizona

 
 

Step 2: Hydration Reaction:

This is an easily recognizable hydration reaction of an alkene to make an alcohol where the alcohol is formed on the # 3 or beta carbon. This is the beginning reaction preparation for the eventual break off of two carbons at a time.

Palmityl-3-ol CoA- Chime in new window

 

 Step 3: Oxidation Reaction:

Again, this reaction should be readily recognized as an oxidation of an alcohol by the coenzyme NAD+ to form a ketone on the #3 or beta carbon.

The NAD+ is converted to NADH + H+ which is a direct link to the electron transport chain. A result of this oxidation reaction is the production of three ATP molecules.

Palmityl-2-one CoA- Chime in new window

 

Step 4: Cleavage by CoA:

The final step is the cleavage of the acetyl CoA from the original fatty acid chain (16 carbons). At the same time, a new CoA molecule makes a new thioester bond to the # 3 or beta carbon carbonyl group. Notice that the final fatty acid molecule attached to the new CoA has two carbons less than when it started (14 carbons).

The 14 carbon-CoA molecule repeats steps 1-4 and finishes as 12 carbon-CoA plus acetyl CoA. The 12 carbon-CoA repeats steps 1-4 and finishes as 10 carbon-CoA plus acetyl CoA. The cycles are repeated until the last cycle begins with a 4 carbon-CoA and finishes as two acetyl CoA molecules. Since the fatty acid cycles have a definite beginning and end, it is better to refer to them as the Fatty Acid Spiral.

Myristyl CoA- Chime in new window

 
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Quiz: How many acetyl CoA are made from the fatty acid spiral of palmitic acid (16 carbons)? Hint: Merely divide 16 by number of carbons in acetyl CoA.  

Example: How many turns of the fatty acid spiral are made for
palmitic acid?

Use the graphic on the left on the bottom. Notice that upon completion of turn #7, the four carbon fragment is split into 2 acetyl CoA groups. An eighth turn of the cycle is unnecessary since the eighth and last acetyl CoA has already been made.

As a general principle, the number of fatty acid spiral turns is always one less than the number of acetyl CoA groups formed. In this example, 8 - 1 = 7 turns of the fatty acid spiral.

Quiz: How many acetyl CoA are made from the fatty acid spiral of lauric acid (12 carbons)? How many turns?