Adenylosuccinate synthase

Enzyme involved in purine nucleotide biosynthesis

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Adenylosuccinate synthase is an enzyme that plays a crucial role in the purine nucleotide cycle, specifically in the biosynthesis of adenosine monophosphate (AMP) from inosine monophosphate (IMP). This enzyme catalyzes the first committed step in the conversion of IMP to AMP, which is a key process in the synthesis of adenine nucleotides.

Structure

Adenylosuccinate synthase is a homodimeric enzyme, meaning it consists of two identical subunits. Each subunit contains a GTP-binding site, which is essential for its catalytic activity. The enzyme's structure has been elucidated through X-ray crystallography, revealing important details about its active site and the binding of substrates.

Function

The primary function of adenylosuccinate synthase is to catalyze the reaction between IMP and aspartate in the presence of GTP, forming adenylosuccinate. This reaction is the first step in the conversion of IMP to AMP, which is a critical pathway in the synthesis of purine nucleotides. The reaction can be summarized as follows:

IMP + Aspartate + GTP _ Adenylosuccinate + GDP + Pi

Mechanism

The enzyme operates through a mechanism that involves the binding of GTP and IMP to the active site, followed by the binding of aspartate. The reaction proceeds with the formation of a covalent intermediate, which is then converted to adenylosuccinate. The release of GDP and inorganic phosphate (Pi) completes the reaction cycle.

Regulation

Adenylosuccinate synthase is regulated by the availability of its substrates and by feedback inhibition. High levels of AMP can inhibit the enzyme, thus regulating the flow of metabolites through the purine nucleotide cycle. This feedback mechanism ensures a balance between the synthesis and utilization of purine nucleotides.

Clinical significance

Mutations or deficiencies in adenylosuccinate synthase can lead to disorders in purine metabolism, which may result in a variety of clinical symptoms. These can include neurological disorders and muscle dysfunction, as the purine nucleotide cycle is important for energy metabolism in muscle and brain tissues.

Related pages

• Purine metabolism
• Adenosine monophosphate
• Inosine monophosphate
• Guanosine triphosphate

Gallery

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  Crystal structure of adenylosuccinate synthase

• Detailed view of the enzyme's active site

Adenylosuccinate_synthase

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