Evolution of glucose utilization: glucokinase and glucokinase regulator protein

Mol Phylogenet Evol. 2014 Jan;70:195-203. doi: 10.1016/j.ympev.2013.09.016. Epub 2013 Sep 25.


Glucose is an essential nutrient that must be distributed throughout the body to provide energy to sustain physiological functions. Glucose is delivered to distant tissues via be blood stream, and complex systems have evolved to maintain the levels of glucose within a narrow physiological range. Phosphorylation of glucose, by glucokinase, is an essential component of glucose homeostasis, both from the regulatory and metabolic point-of-view. Here we review the evolution of glucose utilization from the perspective of glucokinase. We discuss the origin of glucokinase, its evolution within the hexokinase gene family, and the evolution of its interacting regulatory partner, glucokinase regulatory protein (GCKR). Evolution of the structure and sequence of both glucokinase and GCKR have been necessary to optimize glucokinase in its role in glucose metabolism.

Keywords: Glucokinase (GCK); Glucokinase regulatory protein (GCKR); Glucose; Hexokinase (HK); Liver.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Carrier Proteins / genetics*
  • Evolution, Molecular
  • Glucokinase / genetics*
  • Glucokinase / metabolism
  • Glucose / metabolism*
  • Humans
  • Phylogeny*
  • Sequence Analysis, DNA


  • Carrier Proteins
  • glucokinase regulatory protein
  • Glucokinase
  • Glucose