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( Gluconeogenesis) Gluconeogenesis is the generation of glucose from non-sugar carbon substrates like pyruvate, lactate, glycerol, and glucogenic amino acids.

The vast majority of gluconeogenesis takes place in the liver and, to a smaller extent, in the cortex of kidneys. This process occurs during periods of fasting, starvation, or intense exercise and is highly endergonic. Gluconeogenesis is often associated with ketosis.

Many 3- and 4-carbon substrates can enter the gluconeogenesis pathway. lactate from anaerobic respiration in skeletal muscle is easily converted to pyruvate in the liver cells; this happens as part of the Cori cycle. However, the first designated substrate in the gluconeogenic pathway is pyruvate.

Gluconeogenesis cannot be considered to be simply a reverse process of glycolysis, as the three irreversible steps in glycolysis are bypassed in gluconeogenesis. This is done to ensure that glycolysis and gluconeogenesis are not operating at the same time in the cell, making it a futile cycle. Therefore, glycolysis and gluconeogenesis follow reciprocal regulation, that is, cellular conditions, which inhibit glycolysis, may in turn activate gluconeogenesis.

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