Extracting 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 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.

Diagram of 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:

Consumed: 2 ATP
Produced: 8 ATP

Net: 6 ATP
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.