The word gluconeogenesis means the creation (genesis) of glucose from new (neo) sources. Under normal circumstances, carbohydrates are broken down to release glucose. However, under special circumstances such as limited availability of carbohydrates, other molecules such as fatty acids, amino acids and pyruvate are converted to glucose. This is important for humans, as we store only a limited amount of glycogen to maintain blood glucose levels for body cells, including blood and brain cells that relies almost exclusively on glucose for energy. Gluconeogenesis occurs primarily in the liver and kidneys.

So how does gluconeogenesis work? Recall from glycolysis that it has three irreversible reactions. These irreversible reactions can be reversed by certain enzymes that are upregulated when there is a deficiency of glucose. The figures below show these reactions and the gluconeogenic enzymes (in green) responsible for reversing them.

Reaction 1: Converting pyruvate back to phosphoenolpyruvate

Reaction 2: Converting fructose 1, 6 bisphosphate back to fructose-6-phosphate

Reaction 3: Converting glucose-6-phosphate back to glucose

Looking at the Big Picture

For your biochemistry exam, be well familiar with the above steps involved in reversing glycolysis to make glucose. In addition, be aware of the big picture involving the role of amino acids, fatty acids, glycerol and lactate in gluconeogenesis. See the figure below.

Gluconeogenesis – The big picture

You should also know the difference between ketogenic and glucogenic amino acids shown in the diagram below. Glucogenic amino acids are those that can be converted to glucose through gluconeogenesis. Ketogenic amino acids are converted to ketone bodies. Lysine and leucine are the only two purely ketogenic amino acids.

Ketogenic and glucogenic amino acids

Courtney Simons
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Courtney Simons is a food science professor. He holds a BS degree in food science and a Ph.D. in cereal science from North Dakota State University.
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