When the body's stores of carbohydrates decrease below normal, moderate quantities of glucose can be formed from amino acids and the glycerol portion of fat. This process is called gluconeogenesis.
Gluconeogenesis is especially important in preventing an excessive reduction in the blood glucose concentration during fasting. 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. 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 per cent 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.
About 60 per cent of the amino acids in the body proteins can be converted easily into carbohydrates; the remaining 40 per cent have chemical configurations that make this difficult or impossible. Each amino acid is converted into glucose by a slightly different chemical process. For instance, alanine can be converted directly into pyruvic acid simply by deamination; the pyruvic acid is then converted into glucose or stored glycogen. Several of the more complicated amino acids can be converted into different sugars that contain three-, four-, five-, or seven-carbon atoms; they can then enter the phosphogluconate pathway and eventually form glucose. Thus, by means of deamination plus several simple interconversions, many of the amino acids can become glucose. Similar interconversions can change glycerol into glucose or glycogen.
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, as follows.
When glucose is not immediately required for energy, the extra glucose that continually enters the cells is either stored as glycogen or converted into fat. Glucose is preferentially stored as glycogen until the cells have stored as much glycogen as they can—an amount sufficient to supply the energy needs of the body for only 12 to 24 hours.
When the glycogen-storing cells (primarily liver and muscle cells) approach saturation with glycogen, the additional glucose is converted into fat in liver and fat cells and is stored as fat in the fat cells. Other steps in the chemistry of this conversion are discussed in Chapter 68.
Effect of Corticotropin and Glucocorticoids on Gluconeogenesis. When normal quantities of carbohydrates are not available to the cells, the adenohypophysis, for reasons not completely understood, begins to secrete increased quantities of the hormone corti-cotropin. 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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