Urocanase: Difference between revisions

Revision as of 21:00, 9 February 2025

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.

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.

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

References

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-== Urocanase ==
+{{Short description|Enzyme involved in the histidine degradation pathway}}
+{{Use dmy dates|date=October 2023}}
-Urocanase is an enzyme that plays a crucial role in the metabolism of histidine, an essential amino acid. It is responsible for the conversion of urocanic acid to imidazolone propionic acid, which is further metabolized to formiminoglutamic acid. This enzyme is found in various organisms, including bacteria, fungi, plants, and animals.
+'''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 ===
+==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.
-Urocanase is a homodimeric enzyme, meaning it consists of two identical subunits. Each subunit contains approximately 300 amino acids and has a molecular weight of around 33 kDa. The enzyme has been extensively studied in different organisms, and its crystal structure has been determined in several species, including humans and bacteria.
+[[File:PDB_2fkn_EBI.png|thumb|right|Crystal structure of urocanase (PDB ID: 2fkn)]]
-=== Function ===
+==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.
-The primary function of urocanase is to catalyze the conversion of urocanic acid, a metabolite of histidine, to imidazolone propionic acid. This reaction is an essential step in the histidine degradation pathway. Imidazolone propionic acid is subsequently converted to formiminoglutamic acid by the action of another enzyme called imidazolonepropionase.
+==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.
-=== Role in Histidine Metabolism ===
+[[File:Imidazol-4-one-5-propionic_acid.png|thumb|right|Chemical structure of imidazolonepropionic acid]]
-Histidine is an essential amino acid that is obtained through dietary sources. It plays a vital role in protein synthesis, neurotransmission, and the production of various molecules, such as histamine and carnosine. However, excess histidine needs to be metabolized to maintain proper physiological balance.
+==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]].
-Urocanase is involved in the breakdown of histidine, specifically in the conversion of urocanic acid to imidazolone propionic acid. This step allows for the further degradation of histidine and the eventual production of formiminoglutamic acid, which can be further metabolized to produce glutamic acid.
+==Related pages==
+* [[Histidine degradation pathway]]
+* [[Amidohydrolase superfamily]]
+* [[NAD+]]
-=== Clinical Significance ===
+==References==
+{{Reflist}}
-Mutations in the urocanase gene can lead to a rare genetic disorder known as urocanic aciduria. This condition is characterized by the accumulation of urocanic acid in the body, resulting in various symptoms, including intellectual disability, seizures, and developmental delays. Urocanic aciduria is inherited in an autosomal recessive manner.
-=== References ===
-. [[Histidine metabolism|Histidine Metabolism]] - Wikipedia article on histidine metabolism.
-. [[Amino acid metabolism|Amino Acid Metabolism]] - Wikipedia article on amino acid metabolism.
-. [[Urocanic aciduria|Urocanic Aciduria]] - Rare Diseases Database article on urocanic aciduria.
-== See Also ==
-* [[Histidine]]
-* [[Enzyme]]
-* [[Amino Acid Metabolism]]
-* [[Genetic Disorder]]
+[[Category:EC 4.2.1]]
+[[Category:Histidine metabolism]]
 [[Category:Enzymes]]
-[[Category:Amino acids]]
-[[Category:Metabolism]]
-[[Category:Genetic disorders]]