**3. Glucokinase regulates the fate of glucose carbons in the liver**

In order to enter the lipogenic pathway, glucose must be metabolized. The first and ratelimiting step is the phosphorylation of glucose at the 6th carbon to obtain glucose-6 phosphate. This reaction is catalyzed by glucokinase (GK; EC 2.7.1.1), a member of the hexokinase family. However, GK differs from other hexokinases in its particular kinetic properties: affinity for glucose that is within the physiological plasma concentration range (S0.5 for glucose of 8 mM), positive cooperativity for glucose although it is a monomeric enzyme, and lack of inhibition by glucose-6-phosphate (Table 1).


Table 1. Hexokinase family kinetic properties

As a result of its kinetic characteristics, intracellular glucose phosphorylation rate inside the hepatocyte correlates with glycaemia. Hence, GK can be considered an intracellular glucose sensor. Consequently, apart from hepatocytes, GK is expressed in glucosensitive cells of the pancreas, hypothalamus, anterior pituitary gland, and entero-endocrine K and L cells of the gut (Schuit, 2001; Zelent, 2006; Vieira, 2007; Iynedjian, 2009), all of them crucial in the control of the whole-body glucose homeostasis.

Liver contains 99.9% of the body GK. Therefore, is not surprising that this enzyme influences intermediary metabolism and energy storage. GK reaction controls the flux of glucose through several metabolic pathways: glycolysis, glucose oxidization, glycogenesis, triglyceride synthesis, phospholipids and cholesterol synthesis, glycogenolysis and gluconeogenesis. For that reason, GK is an enzyme highly regulated in the liver, both at the transcriptional and the post-transcriptional level.
