Asparagine synthase (glutamine-hydrolysing)
Asparagine synthase (glutamine-hydrolysing), also known as asparagine synthetase (glutamine-hydrolyzing) or EC number 6.3.5.4, is an enzyme that catalyzes the synthesis of asparagine from aspartate, glutamine, and ATP. It plays a crucial role in cellular metabolism by providing asparagine, a non-essential amino acid vital for protein synthesis, nucleotide metabolism, and various other cellular functions.
The reaction catalyzed by asparagine synthase (glutamine-hydrolysing) is:
ATP + L-aspartate + L-glutamine + H2O ⇌ AMP + diphosphate + L-asparagine + L-glutamate
In this reaction, ATP provides the energy necessary to activate the aspartate. The glutamine serves as the nitrogen donor, with its amide nitrogen being transferred to the aspartate to form asparagine. Glutamate is produced as a byproduct of this nitrogen transfer.
Asparagine synthase (glutamine-hydrolysing) is found in a wide range of organisms, including bacteria, fungi, plants, and animals. In mammalian cells, the enzyme is particularly important in rapidly dividing cells, such as cancer cells, which have a high demand for asparagine. This makes asparagine synthase a potential target for cancer therapy. Certain chemotherapeutic drugs target this enzyme to deplete asparagine levels, thereby inhibiting cancer cell growth.
The enzyme's activity is often regulated by the availability of its substrates, asparagine, glutamine, and aspartate. Feedback inhibition by asparagine can also occur.
The systematic name for this enzyme is L-aspartate:L-glutamine amido-ligase (AMP-forming).