Your body can use amino acids to produce glucose. Glucose production in your body is important for maintaining normal blood glucose levels (plasma glucose levels). The process by which your body produces glucose from non-carbohydrate sources is called gluconeogenesis. The liver and to a lesser extent, the kidneys are the key sites for gluconeogenesis. The amino acids that are selectively used for glucose production are isoleucine, phenylalanine, threonine, tryptophan and tyrosine. These amino acids are collectively known as the gluconeogenic amino acids.

Regulation of Blood Glucose

Glucose is a highly regulated metabolite. The body maintains a steady-state plasma glucose level at a value of of 90 to 100 mg per dl. Insulin is the primary hormone for regulating blood glucose. When blood glucose rises above normal levels, excess glucose is taken up by the muscles and utilized for energy or stored as glycogen. Glycogen is a chain of glucose molecules. Significant amounts of the excess glucose is also stored as glycogen in the liver. The rest of the glucose can be stored as fat in the fat cells. This latter effect can lead to obesity.

If the plasma glucose falls below normal levels the body would bring it back to normal levels. This is achieved by releasing glucose from the glycogen stores in the liver. Your liver and kidneys can also produce glucose (gluconeogenesis) to help maintain the steady-state plasma level of glucose. Gluconeogenesis is the primary mechanisms for maintaining the plasma level of glucose in conditions where the body's glucose reserves are markedly lowered.

Importance of Regulating Blood Glucose

Glucose is the only source of energy for the brain and the primary source of energy for most of the other organs in the body. The brain can use other sources of energy such as ketones and ketone bodies under conditions that gradually deplete the body's glucose reserves, such as starvation.Ketone bodies are break-down products of fatty acids. The brain would be deprived of nutrition if plasma glucose goes down sharply and abruptly.

Numerous adverse health consequences can occur when blood glucose deviates significantly from its normal value. Lowered levels of plasma glucose (hypoglycemia) can lead to conditions such as fatigue, confusion, impairment in the ability to concentrate and ataxia (inability to walk). Severe cases of hypoglycemia can result in coma and death. Sustained elevation of plasma glucose can lead to numerous chronic diseases and conditions such as obesity, type 2 diabetes, hypertension, hyperlipidemia, elevated plasma levels of cholesterol, ischemic heart disease, peripheral artery disease, strokes, morbidity and shortened live.

Conversion of Amino Acids to Glucose

Gluconeogenic amino acids are amino acids that can be converted to glucose. All amino acids except for lysine and leucine, are to some extent gluconeogenic, however, the five amino acids that are selectively used for glucose synthesis are isoleucine, phenylalanine, threonine, tryptophan and tyrosine. These amino acids are selectively used for glucose synthesis because they are easily converted to metabolic intermediaries and some of the intermediary metabolites are readily utilized for gluconeogenesis. These metabolic intermediaries are pyruvate, oxaloacetic acid and ketoglutarate. Pyruvate is an intermediary in the glycolytic pathway, whereas, oxaloacetic acid and ketoglutarate are intermediaries in the tricarbolic acid pathway (Krebs cycle).


Gluconeogenesis is activated by depletion of the available glucose for the body's energy metabolism. Consequently,  gluconeogenesis is promoted by factors that accelerate the depletion of the body's glucose, including the depletion of glycogen (the stored glucose). Some of the factors that stimulate gluconeogenesis are:

  • Increase in physical activity such as aerobic exercise

  • Low carbohydrate diet

  • Fasting and starvation

  • Ketosis

  • Decrease in the anabolic effects of insulin