Urocanase

Enzyme involved in the histidine degradation pathway

Urocanase (also known as urocanate hydratase) is an enzyme that catalyzes the reversible hydration of urocanic acid to form imidazolonepropionic acid. This reaction is a part of the histidine degradation pathway in many organisms, including bacteria, fungi, and mammals.

Structure

Urocanase is a member of the amidohydrolase superfamily and typically functions as a homodimer. The enzyme contains a tightly bound NAD+ cofactor, which is unusual because NAD+ is not consumed in the reaction. The structure of urocanase has been elucidated through X-ray crystallography, revealing a complex fold that accommodates the substrate and cofactor.

Crystal structure of urocanase (PDB ID: 2fkn)

Function

Urocanase plays a crucial role in the catabolism of L-histidine, an essential amino acid. The enzyme facilitates the conversion of urocanic acid, which is produced from histidine by the action of histidine ammonia-lyase, into imidazolonepropionic acid. This step is essential for the subsequent production of glutamate and other metabolites.

Mechanism

The enzymatic mechanism of urocanase involves the addition of a water molecule across the double bond of urocanic acid, forming imidazolonepropionic acid. The NAD+ cofactor is believed to stabilize the reaction intermediate, although it is not reduced during the process.

Chemical structure of imidazolonepropionic acid

Biological significance

In humans, urocanase is primarily found in the liver, where it participates in the breakdown of dietary histidine. Deficiency in urocanase activity can lead to the accumulation of urocanic acid, which is excreted in urine, a condition known as urocanic aciduria.

Related pages

• Histidine degradation pathway
• Amidohydrolase superfamily
• NAD+

References

• Structure of Urocanase
  Structure of Urocanase
• 
  Chemical structure of Imidazol-4-one-5-propionic acid