Energy from Fatty Acid and Glucose

by Nickolaos D. Skouras, PhD.

Many cellular processes require energy. Most of these reactions are enzymatically coupled to another, energy liberating, reaction. Coenzyme-A is required to initiate the body's energy cycle (known variously as the ATP, TCA, Krebs, or citric acid cycle), it is constantly expended and constantly needs replenishing. Coenzyme-A converts metabolic energy sources, like sugars and fats into cellular energy. Coenzyme-A also helps the cells deliver fuel to the ATP cycle: carbohydrate from anaerobic (insufficient oxygen in the system) metabolism and fat from aerobic (sufficient oxygen) metabolism.

Adenosine Triphosphate(ATP) and Adenosine Diphosphate(ADP)




Nicotinamide adenine dinucleotide (NADH)

Nicotinamide adenine dinucleotide (NADH), plays a central role in oxidative metabolism. Through the mitochondrial electron transport chain, NADH can transfer two electrons and a hydrogen ion to oxygen, liberating 52.6 kcal/mole. This is enough energy to synthesize 7.2 ATPs from ADP and Pi. However, if Coenzyme-A is not available in sufficient amounts then the human body cannot fully utilize NADH and many of the other nutrients it needs to stay healthy.

Energy from Fatty Acids

Fat molecules consist of three fatty acid chains connected by a glycerol backbone. Fatty acids are basically long chains of carbon and hydrogen and are the major source of energy during normal activities.

Fatty acids are broken down by progressively cleaving two carbon bits and converting these to acetyl Coenzyme-A. The acetyl CoA is then oxidized by the same citric acid cycle involved in the metabolism of glucose. For every two carbons in a fatty acid, oxidation yields 5 ATPs generating the acetyl CoA and 12 more ATPs oxidizing the coenzyme. This makes fat a terrific molecule in which to store energy, as the body well knows (much to our dismay).


The only biological drawback to this, and other, forms of oxidative metabolism is its dependence on oxygen. Thus, if energy is required more rapidly than oxygen can be delivered, muscles switch to the less efficient anaerobic pathways. Interestingly, this implies that an anaerobic workout will not "burn" any fat, but will preferentially deplete the body of glucose. Of course, your body can't survive very long on just anaerobic metabolism...it just can't generate enough energy.

Energy from Glucose

Two different pathways are involved in the metabolism of glucose: one anaerobic and one aerobic. The anaerobic process occurs in the cytoplasm and is only moderately efficient. The aerobic cycle takes place in the mitochondria and is results in the greatest release of energy. As the name implies, though, it requires oxygen.

Anaerobic metabolism

Glucose in the bloodstream diffuses into the cytoplasm and is locked there by phosphorylation. A glucose molecule is then rearranged slightly to fructose and phosphorylated again to fructose diphosphate. These steps actually require energy, in the form of two ATPs per glucose. The fructose is then cleaved to yield two glyceraldehyde phosphates (GPs). In the next steps, energy is finally released, in the form of two ATPs and two NADHs, as the GPs are oxidized to phosphoglycerates. One of the key enzymes in this process is glyceraldehyde phosphate dehydrogenase (GPDH), which transfers a hydrogen atom from the GP to NAD to yield the energetic NADH. Due to its key position in the glycolytic pathway, biochemical assays of GPDH are often used to estimate the glycolytic capacity of a muscle cell. Finally, two more ATPs are produced as the phosphoglycerates are oxidized to pyruvate.

Aerobic metabolism

Pyruvate is the starting molecule for oxidative phosphorylation via the Krebb's, TCA or citric acid cycle. In this process, all of the C-C and C-H bonds of the pyruvate will be transferred to oxygen. The pathway can be seen in the figure below.

The Citric Acid Cycle


Basically, the pyruvate is oxidized to acetyl Coenzyme-A, which can then bind with the four carbon oxaloacetate to generate a six carbon citrate. Carbons and hydrogens are gradually cleaved from this citrate until all that remains is the four carbon oxaloacetate we started with. In the process, four NADHs, one FADH and one GTP are generated for each starting pyruvate.

Energy accounting

Each NADH will be oxidized to NAD, generating three ATPs (although it "costs" one ATP to transfer the NADHs generated during anaerobic metabolism into the mitochondria for reduction). For each molecule of glucose we can calculate the useable energy produced:

Anaerobic
     Consumed:          2 ATP
     Produced:          8 ATP
_____________________________
          Net:          6 ATP

Aerobic
     Consumed:          0 ATP
     Produced:      2x 15 ATP
_____________________________
          Net:         30 ATP

Thus, for each glucose that enters the muscle, up to 36 ATPs can be generated.