Formation of Carbohydrates from Proteins and Fats- “Gluconeogenesis”
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 prevent-ing an excessive reduction in the blood glucose concen-tration 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 pro-duction 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 pro-teins 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 carbohydratesin the cells and decreased blood sugar are the basic stimuli that increase the rate of gluconeogenesis. Dimin-ished carbohydrates can directly reverse many of the glycolytic and phosphogluconate reactions, thus allow-ing the conversion of deaminated amino acids and glycerol into carbohydrates. In addition, the hormone cortisol is especially important in this regulation, asfollows.
Effect of Corticotropin and Glucocorticoids on Gluco- neogenesis. When normal quantities of carbohydratesare 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 producelarge quantities of glucocorticoid hormones, especially cortisol. In turn, cortisol mobilizes proteins fromessentially 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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