Aromatic L-amino acid decarboxylase

Aromatic L-amino acid decarboxylase

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DOPA decarboxylase dimer structure

Aromatic L-amino acid decarboxylase (AADC), also known as DOPA decarboxylase, is an enzyme that catalyzes the decarboxylation of aromatic L-amino acids to produce their corresponding amines. This enzyme plays a crucial role in the biosynthesis of several important neurotransmitters, including dopamine, serotonin, and histamine.

Structure

Aromatic L-amino acid decarboxylase is a homodimeric enzyme, meaning it consists of two identical subunits. Each subunit contains a pyridoxal phosphate (PLP) cofactor, which is essential for the enzyme's catalytic activity. The enzyme's structure has been elucidated through X-ray crystallography, revealing details about its active site and the binding of substrates and cofactors.

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Crystal structure of aromatic L-amino acid decarboxylase

Function

AADC is responsible for the decarboxylation of L-DOPA to dopamine, 5-hydroxytryptophan to serotonin, and histidine to histamine. These reactions are critical steps in the biosynthetic pathways of these neurotransmitters, which are vital for normal neurological function.

Mechanism

The enzyme operates through a mechanism involving the formation of a Schiff base between the PLP cofactor and the substrate. This intermediate facilitates the removal of the carboxyl group from the substrate, resulting in the formation of the corresponding amine.

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Mechanism of action of aromatic L-amino acid decarboxylase

Clinical Significance

Deficiencies in AADC activity can lead to a rare genetic disorder known as AADC deficiency, characterized by a lack of dopamine and serotonin production. This condition results in severe developmental and neurological symptoms, including movement disorders and autonomic dysfunction.

Pathways

AADC is involved in several key metabolic pathways:

• Dopamine biosynthesis: Converts L-DOPA to dopamine, a critical neurotransmitter in the central nervous system.
• Serotonin biosynthesis: Converts 5-hydroxytryptophan to serotonin, which is involved in mood regulation and other functions.
• Histamine biosynthesis: Converts histidine to histamine, which plays a role in immune response and gastric acid secretion.

Pathway of serotonin biosynthesis

Related Pages

• Dopamine
• Serotonin
• Histamine
• Pyridoxal phosphate
• Neurotransmitter

External Links

• Aromatic L-amino acid decarboxylase on Wikipedia