Nucleoside-diphosphate kinases (NDKs, also NDP Kinase, (poly)nucleotide kinases and nucleoside diphosphokinases) are enzyme

Enzyme

Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...

s that catalyze the exchange of phosphate groups between different nucleoside diphosphate

Nucleotide

Nucleotides are molecules that, when joined together, make up the structural units of RNA and DNA. In addition, nucleotides participate in cellular signaling , and are incorporated into important cofactors of enzymatic reactions...

s. NDK activities maintain an equilibrium between the concentrations of different nucleoside triphosphates such as, for example, when GTP

Guanosine triphosphate

Guanosine-5'-triphosphate is a purine nucleoside triphosphate. It can act as a substrate for the synthesis of RNA during the transcription process...

 produced in the citric acid (Krebs) cycle

Citric acid cycle

The citric acid cycle — also known as the tricarboxylic acid cycle , the Krebs cycle, or the Szent-Györgyi-Krebs cycle — is a series of chemical reactions which is used by all aerobic living organisms to generate energy through the oxidization of acetate derived from carbohydrates, fats and...

 is converted to ATP

Adenosine triphosphate

Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...

.

Function

The overall effect of NDKs is to transfer a phosphate group from a nucleoside triphosphate to a nucleoside diphosphate. Starting with adenosine diphosphate

Adenosine diphosphate

Adenosine diphosphate, abbreviated ADP, is a nucleoside diphosphate. It is an ester of pyrophosphoric acid with the nucleoside adenosine. ADP consists of the pyrophosphate group, the pentose sugar ribose, and the nucleobase adenine....

 GTP and ADP, the activity of NDK produces GDP and ATP.

GTP + ADP → GDP + ATP

Behind this apparently simple reaction is a multistep mechanism. The key steps are

• NDK binds a nucleoside triphosphate (NTP)
• NDK transfers a phosphate to itself, leaving a bound nucleoside diphosphate (NDP)
• NDK releases the bound nucloside diphosphate
• NDK binds another nucleoside diphosphate
• NDK transfers the phosphate to the diphosphate, creating a bound nucleoside triphosphate
• NDK releases the new nucleoside triphosphate

Each step is part of a reversible process, such that the multistep equilibrium is of the following form.

NDK + NTP ↔ NDK~NTP ↔ NDK-P~NDP ↔ NDK-P + NDP

For the transfer of a phosphate from ATP to GDP, the reaction would proceed as

NDK + ATP → NDK~ATP → NDK-P~ADP → NDK-P + ADP →

NDK-P + GDP → NDK-P~GDP → NDK~GTP → NDK + GTP

Eukaryotic systems

There are two isoforms of NDK in humans: NDK-A and NDK-B. Both have very similar structure, and can combine in any proportion to form functional NDK hexamers.