Gluconeogenesis

Gluconeogenesis is the process by which noncarbohydrate molecules are converted to glucose. Lactate, pyruvate, glycerol, propionate, glucogenic amino acids, and pyruvate are the main precursors and substrates for gluconeogenesis.

Location of gluconeogenesis

While certain precursors are made in the mitochondria, the cytosol is where glucose synthesis primarily takes place. Gluconeogenesis occurs mostly in the liver (where 1 kg of glucose is synthesised daily) and to a lesser amount in the renal matrix (where it accounts for roughly 10% of the liver's capacity).

Importance of gluconeogenesis 

A vital role in metabolism, glucose's constant supply is necessary for the body to perform a multitude of tasks.

1. The kidney medulla, erythrocytes, brain, and central nervous system rely on glucose as a constant source of energy. Out of the approximately 160 g of glucose required by the body as a whole, the human brain alone needs about 120 g per day.

2. The only source of energy available to the skeletal muscle in anaerobic environments is glucose.

3. To meet the body's baseline needs for glucose and to keep the intermediates of the citric acid cycle intact, gluconeogenesis must take place during fasting lasting more than a day. Both human survival and the survival of other creatures depend on this. 

4. Some metabolites, such as lactate, glycerol, propionate, and others, that are created in the tissues build up in the blood. They are efficiently removed from the blood by gluconeogenesis. 

Gluconeogenesis from amino acids (protein)

 With the exception of leucine and lysine, the carbon skeleton of glucogenic amino acids forms pyruvate or the citric acid cycle's intermediates, which lead to the synthesis of glucose. 

Gluconeogenesis from glycerol 

Triacylglycerols, which are fats hydrolyzed to release glycerol, are mostly released in adipose tissue. Glycerokinase, an enzyme that is present in the liver and kidney but missing in adipose tissue, converts glycerol into glycerol 3-phosphate. The latter is transformed by glycerol 3-phosphate dehydrogenase into dihydroxyacetone phosphate. Dihydroxyacetone phosphate is a glycolysis intermediate that is easily utilised to produce glucose.

Gluconeogenesis from propionate

A three-carbon propionyl CoA is produced by the oxidation of odd chain fatty acids and the degradation of certain amino acids (methionine, isoleucine). In the presence of ATP and biotin, propionyl CoA carboxylase acts on this to convert it to methyl malonyl CoA, which is subsequently converted to succinyl CoA in the presence of B12 coenzyme. The citric acid cycle allows succinyl CoA, which is generated from propionyl CoA, to enter gluconeogenesis.

References: "Biochemistry’ Satyanarayana and Chakrapani