Aspartokinase

Aspartokinase

Aspartokinase is an enzyme that plays a crucial role in the biosynthesis of amino acids in bacteria, fungi, and plants. It catalyzes the phosphorylation of aspartate, which is the first step in the biosynthetic pathway leading to the production of several essential amino acids, including lysine, methionine, and threonine.

Structure

Aspartokinase is a homodimeric enzyme, meaning it consists of two identical subunits. Each subunit contains an active site where the substrate, aspartate, binds. The enzyme requires ATP as a cofactor, which donates the phosphate group that is transferred to aspartate.

Function

The primary function of aspartokinase is to catalyze the conversion of L-aspartate to L-aspartyl-4-phosphate. This reaction is the first committed step in the biosynthesis of the aspartate family of amino acids. The reaction can be summarized as follows:

L-aspartate + ATP → L-aspartyl-4-phosphate + ADP

This reaction is crucial because it commits the aspartate molecule to the pathway that will eventually lead to the synthesis of lysine, methionine, and threonine.

Regulation

Aspartokinase is subject to feedback inhibition by the end products of its pathway. In many organisms, the enzyme is inhibited by lysine, threonine, or methionine, depending on the specific isoform of the enzyme. This feedback inhibition is a form of allosteric regulation, where the binding of an inhibitor to a site other than the active site causes a conformational change that reduces the enzyme's activity.

Isoforms

In some organisms, multiple isoforms of aspartokinase exist, each with different regulatory properties. For example, in *Escherichia coli*, there are three isoforms of aspartokinase, each regulated by different end products:

• Aspartokinase I is inhibited by threonine.
• Aspartokinase II is inhibited by lysine.
• Aspartokinase III is inhibited by both lysine and threonine.

This allows the organism to finely tune the production of these amino acids based on cellular needs.

Clinical Significance

While aspartokinase is not present in humans, it is a target for antibiotic development. Inhibiting aspartokinase in pathogenic bacteria can disrupt their ability to synthesize essential amino acids, thereby limiting their growth and survival.

Also see

• Amino acid biosynthesis
• Feedback inhibition
• Enzyme regulation
• Lysine biosynthesis
• Threonine