Uracil dehydrogenase

Uracil Dehydrogenase

Uracil dehydrogenase is an enzyme that plays a crucial role in the metabolism of uracil, a pyrimidine nucleobase found in RNA. This enzyme is responsible for the conversion of uracil to dihydrouracil, which is further metabolized to β-alanine. Uracil dehydrogenase is found in various organisms, including bacteria, fungi, plants, and animals.

Structure

Uracil dehydrogenase is a homodimeric enzyme, meaning it consists of two identical subunits. Each subunit contains a catalytic domain responsible for the enzymatic activity and a cofactor-binding domain that binds to the necessary cofactors for the enzyme's function. The enzyme's active site contains residues that are essential for the binding and conversion of uracil.

Function

The primary function of uracil dehydrogenase is to catalyze the oxidation of uracil to dihydrouracil. This reaction involves the transfer of two electrons and two protons, resulting in the formation of dihydrouracil. The enzyme utilizes a flavin adenine dinucleotide (FAD) cofactor as an electron acceptor during the reaction.

Uracil dehydrogenase is an important enzyme in the pyrimidine degradation pathway. After the conversion of uracil to dihydrouracil, dihydrouracil is further metabolized to β-alanine by dihydropyrimidine dehydrogenase. β-alanine is then utilized in various metabolic processes, including the synthesis of proteins and the production of neurotransmitters.

Role in Health and Disease

Uracil dehydrogenase plays a crucial role in maintaining the balance of pyrimidine nucleobases in the body. Dysregulation or deficiency of this enzyme can lead to various health conditions. For example, a deficiency of uracil dehydrogenase activity is associated with dihydropyrimidine dehydrogenase deficiency (DPD deficiency), a rare genetic disorder. DPD deficiency can result in severe toxicity when certain medications, such as fluoropyrimidines used in cancer treatment, are administered.

References

1. Uracil 2. Pyrimidine metabolism 3. Flavin adenine dinucleotide 4. Dihydropyrimidine dehydrogenase 5. β-alanine 6. Dihydropyrimidine dehydrogenase deficiency