Kinases are a group of enzymes that catalyzes the interchange of phosphate groups between rich in energy phosphorylated compounds and diverse substrates.
These enzymes are very important:
a) In increasing the energetic level of different compounds, converting them in metabolically active molecules.
b) In the generation of ATP, GTP, in metabolic pathways.
c) In the covalent modification of enzymes activity.
The typical kinase enzyme catalyzes the following reaction:
Substrate + ATP ———-> Substrate-(P) + ADP
Usually the common names of kinases are based on the substrate that is phosphorylated:
– Glucokinase: the substrate is glucose.
Glucose + ATP ———–> Glucose 6 (P) + ADP
– Hexokinase: The substrate is a hexose (this enzyme is less specific than glucokinase)
Hexose + ATP ————> Hexose (P) + ADP
– Phosphofructokinase (PFK): The substrate is fructose phosphate.
Fructose 6 (P) + ATP —–> Fructose 1, 6 bis (P) + ADP (PFK-1)
Fructose 6 (P) + ATP——> Fructose 2, 6 bis (P) + ADP (PFK-2)
– Protein Kinase: The substrate is a Protein
Protein + ATP ————-> Protein-(P) + ADP
– Tyrosine kinase: The substrate is a residue of tyrosine in a protein (In a strict sense, tyrosine kinase is a kind of Protein kinase).
In some cases, ATP or GTP are formed by the transfer to ADP or GDP of a phosphate of the substrate, which is linked through a rich in energy bond.
The reaction of pyruvate kinase:
Phosphoenol pyruvate +ADP——-> Pyruvate + ATP
Reaction of phosphoglycerokinase (This is an exception among kinases, since this reaction is reversible)
1,3 bisphosphoglycerate + ADP< ——–> 3 Phosphoglycerate + ATP
Besides the importance of kinases in activating metabolites and generating ATP, the phosphorylation of enzymes and other proteins through the action of kinases is a general mechanism of metabolic control at a molecular level.
The activity of several enzymes is controlled by covalent modification based on the addition or remotion of Phosphate groups. Some enzymes increase their activity when phosphorylated, while in other enzymes the activity is decreased. The opposite is valid also for the dephosphorylation of enzymes: while some of them increase the activity when dephosphorylated, others decrease the activity.
Protein Kinases (enzymes that phosphorylate proteins) and Protein Phosphatases (enzymes that release phosphates from proteins) are responsible of maintaining the appropriate equilibrium in several metabolic processes.
A very clear example of this process is seen in the regulation of glycogen metabolism:
Protein kinases (Phosphorylase kinase and Protein Kinase A) provoke phosphorylation of Glycogen phosphorylase and Glycogen Synthase respectively. As a consequence, the activity of Glycogen Phosphorylase increases and the activity of Glycogen Synthase decreases. Global Result: Increase in the conversion of glycogen to glucose.
Phosphatases provoke the release of the phosphates from Glycogen Phosphorylase and from Glycogen Synthase. As a consequence, the activity of Glycogen Phosphorylase decreases and the activity of Glycogen Synthase increases. Global result: An increase in the incorporation of glucose to glycogen.
Particular interest shows the activity of Tyrosine Kinase.
This enzyme is part of a receptor-enzyme molecule, which is activated by the interaction of the part of the molecule that acts as receptor, with some hormones, like insulin, and growth factors. The enzyme then autophosphorylates the tyrosine residues in the enzymatic part of the molecule, gaining in activity and phosphorylating other proteins, like IRSs.
In summary, Kinases, through the catalysis of the interchange of phosphate groups between rich in energy phosphorylated compounds and diverse substrates facilitate very different metabolic process of great relevance for the organism.