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# Asparagine

There are total twenty $\alpha$-amino acids which involve in various protein synthesis processes in living bodies. Proteins are polypeptide form by the condensation polymerization of amino acids.

The monomer units of protein that is amino acids, are bi-functional molecules with amino and carboxyl group positioned in one molecule at alpha carbon atom. Both functional groups involve in condensation reaction to produce peptide through peptide bond which is an amide linkage between amino group and carboxyl group of amino acids.
Hence the polymerization of amino acids forms a long polypeptide chain with N-terminal and C-terminal. Both terminals can continue the polymerization and form different proteins. The physical and chemical properties of proteins depend upon the sequence and type of amino acids involve in peptide bond.

These polypeptide chains oriented in two and three dimensional space in different ways and form various levels of proteins, primary, secondary, tertiary and quaternary proteins.

Hence, the amino group (-NH-) and carbonyl group(-CO-) make the backbone of protein chain, in which one group, amino group is hydrogen donor and another is an acceptor of hydrogen bonds. There is a side chain on each amino acid which vary in their size, shape, charge and polarity all amino acids.

These various side chains are responsible for the three-dimensional structure of protein chains and their function. On the basis of side-chains, they can be classified into three types, hydrophobic, charge and polar. Hydrophobic side-chains are present in the interior for water-soluble proteins and charge parts are usually on the surface.

## Asparagine Amino Acid

Asparagine (abbreviated as Asn or N) is a non-essential amino acid which coded as AAU and AAC. It has one carboxamide group on the side chain with one amino and carboxyl group on alpha carbon atom. Hence it can consider as amide of aspartic acid. It is a neutral, polar and uncharged amino acid in any biologically relevant pH conditions.

The amide group of asparagine can be easily hydrolyzed to carboxyl group and form aspartic acid. This conversion is related to the molecular basis of aging. It located on the surface as well inside the proteins due to the ability of formation of hydrogen bond through amide group of molecule. It also acts as a common site for the bonding of carbohydrates in glycoproteins.

Since asparagine is a non-essential amino acid, it can be easily synthesized by central metabolic pathway intermediates in living system, hence not required in the diet. Asparagine is found in eggs, beef, whey, seafood, nuts, asparagus, whole grains, poultry and potatoes. It was first isolated in from asparagus juice in 1806 and named as Asparagine was the first amino acid to be isolated.

The precursor of biosynthesis of asparagine is oxaloacetate which reacts with glutamate to form aspartate and $\alpha$-ketoglutarate in the presence of transaminase enzyme. In next step, aspartate reacts with glutamine to form asparagine and glutamate is regenerated in the presence of asparagine synthetase enzyme.

The second step involves the conversion of ATP to AMP and pyrophosphate to provide energy during reaction.

Although it is a non-essential amino acid, yet the low levels of asparagine may results poor metabolism or synthesis of aspartic acid in body. The high concentration of aspartic acids can result in the inability to properly synthesize and excrete urea. The presence of excess of urea and inability to excrete urea can form many nitrogen-containing toxic metabolites which can lead to headaches, irritability, or, in extreme cases, confusion, depression, psychosis.

Asparagine is used to form aspartic acid and ammonia in certain biochemical reactions catalyzed by enzyme like asparaginease. Further aspartic acid can converted into oxalo acetic acid which involves the citric acid cycle and ammonia formed urea. Asparagine is also involved in maintenance of central nervous system, metabolism in the brain and essential for the proper functioning and health of our nerves and other cells of the body.

Since asparagine is directly linked with aspartic acid, hence deficiency of one amino acid leads to the deficiency of other one. The deficiency of aspartic acid decreases the synthesis of urea which may lead to accumulation of nitrogen containing toxic substances in the blood. The presence of toxic substances in blood stream directly affects brain and lead to many disorders.

## Asparagine Structure

The IUPAC name of asparagine is 2-Amino-3-carbamoylpropanoic acid with one carbamyl group in side chain of amino acid molecule. The molecular formula of asparagine is C4H8N2O3 with molecular mass 132.12 g $mol^{-1}$. The $pK_{a}$ value of $\alpha$-COOH is 2.0 and for a -NH3+is 8.8 in asparagine molecule. Like other amino acids, asparagine is also an optically active molecule and can exist in dextrorotatory and levorotatory forms.

On the basis of the position of amino group and carboxyl group, molecule can show two configurations D and L.

Due to the presence of non-polar side chain, the overall molecule of asparagine is uncharged as exist in the form of zwitter ion. In acidic medium, zwitterion exists in form of positively charged ion and move towards cathode during electrolysis. While in basic medium, it exists in the form of negatively charged ion and move towards anode.

At isoelectric point there will be no overall movement of ions in solution. The $pK_{a1}$ for $\alpha$-carboxyl group, $pK_{a2}$ for $\alpha$-ammonium ion, and $pK_{a3}$ for side chain group can decide the value of isoelectric point (pI).

Since the side chain of asparagine is neutral in nature the $pK_{a1}$ is equals to 2.02, $pK_{a2}$ is 8.80, hence the isoelectric point will be average of, these two $pK_{a}$ values.

pI = 1/2 ($pK_{a1}$+ $pK_{a2}$)
pI = 5.41

## Asparagine Synthetase

Asparagine synthetase also known as aspartate-ammonia ligase, symbolic as ASNS is an enzyme involve in the biosynthesis of asparagine from aspartate through an ATP-dependent transaminated reaction.

This conversion takes place in the presence of glutamine which acts as amino group donor in reaction.
Two type of Asparagine synthetase are found in Escherichia coli, Asparagine synthetase A(AsnA) and Asparagine synthetase B(AsnB). AsnA which composed of a dimer of monomer AsnA , is involve in catalysis of ammonia-dependent conversion of aspartate to asparagine.

AsnA is the more active compare to AsnB in Escherichia coli which involves in catalytic process of glutamine dependent and ammonia-dependent conversion of aspartate to asparagine. It can also catalyzes the synthesis of asparagine from aspartate, glutamine, and ATP. The main difference between ASAN is that AsnB does not have a histidine in its conserved glutamine aminotransferase domain.

The conversion of aspartate to asparagine is a two step process which catalyzed by Asparagine synthetase (AsnA) with ATP and ammonia as substracts.

The ATP molecule involves in activation of $\gamma$-carboxylate group of aspartate and form an aminoacyl-AMP with pyrophosphate before its amidation by a nucleophilic attack with an ammonium ion. The mechanism of activation by ATP is quite similar to the mechanism used by aminoacyl-tRNA synthetases. At the same time glutamine is getting hydrolyzed at a 2nd site and the intermediate ammonia diffuses through an inter-domain protein tunnel from the site of production to the site of utilization.

The rate of hydrolysis of glutamine is no depending upon the activation of aspartate, hence the two active sites reaction rates are essentially un-coupled from each other.

The X-ray diffraction analysis at 2.5 Å… resolutions proves that the crystal structure of E. Coli asparagine synthetase shows remarkable similarities with the catalytic domain of yeast aspartyl-tRNA synthetase. Both enzymes show common reaction mechanism through the formation of an aminoacyl-adenylate intermediate.

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