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'''Asparagine Synthetase''' (ASNS) is an enzyme that catalyzes the conversion of Aspartic Acid to Asparagine through an ATP dependent amination reaction, using Mg2+ as a co-factor. ASNS can be found in both plants and mammals, however, in plants there are two forms ASNS-A and ASNS-B. Both forms use the same starting molecule of Aspartic Acid and produce Asparagine, the only difference coming from the source of the Nitrogen. ASNS-A uses inorganic Nitrogen in the form of ammonia or diatomic Nitrogen and ASNS-B uses Glutamine as its Nitrogen source; ASNS-B will be the focus of this page because it is very similar and undergoes the same reaction as ASNS in mammals. ASNS is in almost every somatic mammalian cell but is expressed in exponentially higher concentrations in the pancreas.

<scene name='56/564042/Glutamine_amidotransferase/1'>Glutamine Amidotransferase Type-2</scene> (residues 2-191) and and <scene name='56/564042/Asparagine_synthetase_complex/1'>Asparagine Synthetase</scene> complex (residues 213-536). There are two specific domains that contain the substrate binding sites. The N-terminal domain which contains two layers of anti-parallel beta sheets comprised of six layers each,(site PDB)this is where the Glutamine binds. A C-terminal domain also exists, it is comprised of five parallel beta sheets with alpha helices on either side of it, (site PDB) this is where the Mg2+, ATP and Aspartic Acid bind. The two active sites contained within the terminal domains are linked together by a tunnel of hydrophobic and polar surface amino acid residues. Specifically <scene name='56/564042/Residue_365/1'>Residue 365</scene> is important for the binding of the Beta-Asparty-AMP intermediate into the enzyme.  

L-Asparaginase is a naturally occurring enzyme in bacteria that breaks down Asparagine. This easy breakdown of Asparagine into Aspartic Acid and Ammonia by L-Asparagine is able to suppress tumor cell growth cause by lymphoblastic leukemia cells by depleting the Asparagine stores creating a shortage in the plasma of the cell that cannot be compensated for potentially leading to apoptosis of the cell. (site DRL)Sometimes L-Asparaginase activity does not work to suppress the tumor cells. A recent study has been conducted to see if what could potentially cause some cells to be susceptible to treatment and others not be from within the same system. Leukemia infected cell lines were analyzed to see which ones were L-Asparaginase treatment immune and then those cell lines analyzed for protein expression and composition. It was found that in the cell lines that were immune to treatment there was an over expression of ASNS and therefore, an over expression of Asparagine to be used for maintenance and growth of the cells plasma. These findings are being evaluated and a potential new approach to treat lymphoblastic leukemia by using techniques such as RNAi silencing to suppress ASNS activity and allow L-Asparaginase to induce apoptosis in the cancerous cells.

A recent study has shown that a using a adenylated sulfoxmine transition-state analogue 1 has the ability to inhibit human ASNS. This inhibition of the continual production of Asparagine has also been able to suppress the growth of L-Asparaginase resistant Leukemia mouse cell lines.

Recent studies have been trying to find a potential link between the amount of ASNS activity in certain cell cultures as a precursor for L-Asparaginase activity. L-Asparaginase is an enzyme that degrades Asparagine and has been used since the 1970's in basic cancer treatment plans for acute lymphoblastic leukemia (site MCT). The body will naturally secrete L-Asparaginase as a response to a potential forming tumor or potential cancer cell aggregation. These studies are finding a correlation between the amount of ASNS being expressed prior to the expression of L-Asparaginase synthetase, since L-Asparaginase has only been shown to help combat lymphoblastic leukemia this would not be a direct treatment but rather an indicator that something is happening that requires attention and hopefully allow doctors to screen for ASNS activity and catch ovarian cancer in it's earlier stages when it is more treatable and easier to remove from the body.