Aspartase

Enzyme involved in the conversion of aspartate to fumarate

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Identifiers
EC number	4.3.1.1
CAS number	9013-03-0
Alt. names
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway

Aspartase is an enzyme that catalyzes the reversible deamination of L-aspartate to fumarate and ammonia. This reaction is an important step in the aspartate metabolism pathway and plays a crucial role in the citric acid cycle and nitrogen metabolism.

Structure

Aspartase is a homotetrameric enzyme, meaning it consists of four identical subunits. Each subunit contains an active site where the substrate, L-aspartate, binds. The enzyme requires a divalent metal ion, such as magnesium or manganese, for its activity. The structure of aspartase has been studied using X-ray crystallography, revealing details about its active site and the mechanism of catalysis.

Function

The primary function of aspartase is to catalyze the conversion of L-aspartate to fumarate and ammonia. This reaction is part of the aspartate ammonia-lyase pathway, which is involved in the degradation of aspartate. The reaction can be represented as follows:

L-aspartate → fumarate + NH₃

This reaction is important for the regulation of nitrogen levels in the cell and contributes to the pool of fumarate, which is a key intermediate in the citric acid cycle.

Mechanism

Aspartase catalyzes the deamination of L-aspartate through a mechanism that involves the formation of a carbanion intermediate. The enzyme stabilizes this intermediate, facilitating the elimination of ammonia and the formation of fumarate. The presence of a divalent metal ion in the active site is crucial for stabilizing the negative charges that develop during the reaction.

Clinical significance

Deficiencies or malfunctions in aspartase activity can lead to metabolic disorders. Although rare, such deficiencies can disrupt the balance of nitrogen metabolism and the citric acid cycle, leading to an accumulation of aspartate and related metabolites. Understanding the function and regulation of aspartase is important for developing therapeutic strategies for these conditions.

Research applications

Aspartase is used in various research applications, particularly in studies of amino acid metabolism and enzyme catalysis. It serves as a model enzyme for studying the mechanisms of lyase reactions and the role of metal ions in enzyme activity.

Also see

• Aspartate metabolism
• Citric acid cycle
• Enzyme catalysis
• Nitrogen metabolism