Glukokinaasin

Glukokinaasin is a variant spelling of glucokinase, an enzyme that catalyzes the first step in glucose metabolism: the phosphorylation of glucose to glucose-6-phosphate using ATP. In humans, glucokinase is encoded by the GCK gene and is expressed predominantly in the liver and pancreatic beta cells, with activity also detected in smaller amounts in other tissues such as the intestine. The enzyme serves a dual role: in pancreatic beta cells, it functions as a glucose sensor that helps regulate insulin secretion; in the liver, it provides glucose-6-phosphate for glycolysis and glycogen synthesis, contributing to blood glucose homeostasis.

Biochemical properties of glucokinase distinguish it from other hexokinases. It has a relatively high Km for glucose (roughly in the millimolar range), meaning its activity rises when blood glucose levels are elevated. This high-threshold kinetics makes glucokinase well suited as a metabolic glucose sensor in beta cells and as a regulator of hepatic glucose utilization. Glucokinase activity is modulated by its regulatory protein, GKRP, in the liver. GKRP can bind glucokinase and sequester it in the nucleus, reducing its activity; metabolites such as fructose-1-phosphate promote the release of glucokinase from GKRP, increasing cytosolic activity. Insulin can upregulate GCK expression in the liver and pancreas, aligning enzyme abundance with metabolic demand.

Clinically, GCK mutations cause maturity-onset diabetes of the young type 2 (MODY2), typically presenting as mild, stable fasting hyperglycemia. The condition often requires minimal treatment beyond lifestyle management, though some individuals may need pharmacotherapy. Glucokinase activators have been explored as potential treatments for type 2 diabetes by lowering the glucose threshold for insulin release and hepatic glucose utilization, though development has faced safety and efficacy challenges.