Gluconeogenesis is a metabolic pathway of glucose formation from amino acids and the glycerol portion of fat.
About 60 percent of the amino acids in the body proteins can be converted easily into carbohydrates; the remaining 40 percent have chemical configurations that make this difficult or impossible. Each amino acid is converted into glucose by a slightly different chemical process.
For example, alanine can be converted directly into pyruvic acid simply by deamination; the pyruvic acid is then converted into glucose or stored glycogen.
Glucose is the primary substrate for energy in tissues such as the brain and the red blood cells, and adequate amounts of glucose must be present in the blood for several hours between meals. Gluconeogenesis is especially important in preventing an excessive reduction in the blood glucose concentration during fasting.
The liver plays a key role in maintaining blood glucose levels during fasting by converting its stored glycogen to glucose (glycogenolysis) and by synthesizing glucose, mainly from lactate and amino acids (gluconeogenesis).
Approximately 25 percent of the liver’s glucose production during fasting is from gluconeogenesis, helping to provide a steady supply of glucose to the brain. During prolonged fasting, the kidneys also synthesize considerable amounts of glucose from amino acids and other precursors.
Regulation of Gluconeogenesis
Diminished carbohydrates in the cells and decreased blood sugar are the basic stimuli that increase the rate of gluconeogenesis. Diminished carbohydrates can directly reverse many of the glycolytic and phosphogluconate reactions, thus allowing the conversion of deaminated amino acids and glycerol into carbohydrates.
In addition, the hormone cortisol is especially important in this regulation. When normal quantities of carbohydrates are not available to the cells, the adenohypophysis begins to secrete increased quantities of the hormone corticotropin. This stimulates the adrenal cortex to produce large quantities of glucocorticoid hormones, especially cortisol.
In turn, cortisol mobilizes proteins from essentially all cells of the body, making these available in the form of amino acids in the body fluids. A high proportion of these immediately become deaminated in the liver and provide ideal substrates for conversion into glucose. Thus, one of the most important means by which gluconeogenesis is promoted is through the release of glucocorticoids from the adrenal cortex.
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