Gluconeogenesis

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Gluconeogenesis is the generation of new glucose molecules from other substrates, as opposed to its generation from glycogen breakdown. Like many metabolic pathways it happens mostly in the liver, and is triggered by the action of glucagon. The kidney can also carry out gluconeogenesis, but to a limited extent. Cortisol and Growth Hormone also stimulate gluconeogenesis.

Gluconeogenesis begins with various substrates converted into pyruvate, and this proceeds through what is essentially the reverse of glycolysis (except for a few differing enzymes). The majority of the enzymes responsible for gluconeogenesis are found in the cytoplasm; the exception is pyruvate carboxylase which is located in the mitochondria. Most factors that regulate the activity of the gluconeogenesis pathway do so by inhibiting the activity of key enzymes. However, both acetyl CoA and citrate activate gluconeogenesis enzymes (pyruvate carboxylase and fructose 1,6 bisphosphatase, respectively).

Many 3 and 4-carbon substrates can enter the gluconeogenesis pathway. Lactate from anaerobic exercise in skeletal muscle is easily converted to pyruvate; this happens as part of the Cori cycle.

Oxaloacetate (an intermediate in the citric acid cycle) can also be used for gluconeogenesis. Amino acids, after their amino group has been removed, feed into parts of the citric acid cycle, and can thus can generate glucose in this pathway.

Most fatty acids cannot be turned into glucose unless the glyoxylate cycle is used, the exception being odd-chain fatty acids which can yield proprionyl CoA, a precursor for oxaloacetate. Fatty acids are regularly broken down into the two carbon acetyl CoA, which becomes degraded in the citric acid cycle. In contrast glycerol, which is a part of all triacylglycerols, can be used in gluconeogenesis.

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