Gluconeogenesis 

Gluconeogenic precursors include glycerol released during triacylglycerol hydrolysis in adipose tissue, lactate released by cells that lack mitochondria and by exercising skeletal muscle, and α-keto acids (for example, α-ketoglutarate and pyruvate) derived from glucogenic amino acid metabolism (Fig. 1). Seven of the reactions of glycolysis are reversible and are used for gluconeogenesis in the liver and kidneys. Three reactions, catalyzed by pyruvate kinase, phosphofructokinase-1, and glucokinase/hexokinase, are physiologically irreversible and must be circumvented. Pyruvate is converted to oxaloacetate and then to phosphoenolpyruvate (PEP) by pyruvate carboxylase (PC ) and PEPcarboxykinase (PEPCK ). PC requires biotin and ATP and is allosterically activated by acetyl coenzyme A. PEPCK requires guanosine triphosphate.
Transcription of its gene is increased by glucagon and cortisol and decreased by insulin. Fructose 1,6-bisphosphate is converted to fructose 6-phosphate by fructose 1,6-bisphosphatase. This enzyme is inhibited by a high adenosine monophosphate (AMP)/ATP ratio. It is also inhibited by fructose 2,6-bisphosphate, the primary allosteric activator of glycolysis.
Glucose 6-phosphate is dephosphorylated to glucose by glucose 6-phosphatase. This enzyme of the endoplasmic reticular membrane catalyzes the final step in gluconeogenesis and in glycogen degradation. Its deficiency results in severe, fasting hypoglycemia.

Figure 1: Key concept map for gluconeogenesis. TCA = tricarboxylic acid. CoA = coenzyme A; cAMP = cyclic adenosine monophosphate; P = phosphate; (B)PG = (bis)phosphoglycerate; G = glyceraldehyde; F = fructose; CO2 = carbon dioxide.