Dihydropyrimidinase

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Dihydropyrimidinase is an enzyme that plays a crucial role in the pyrimidine degradation pathway. It catalyzes the reversible hydrolytic ring opening of dihydropyrimidines to N-carbamoyl-β-alanine and N-carbamoyl-β-aminoisobutyric acid. This enzyme is essential for the proper metabolism of pyrimidine bases such as thymine and uracil.

Function

Dihydropyrimidinase is involved in the second step of the pyrimidine degradation pathway. The enzyme facilitates the conversion of dihydropyrimidines, which are produced from the reduction of pyrimidine bases, into N-carbamoyl-β-alanine and N-carbamoyl-β-aminoisobutyric acid. These products are further processed into β-alanine and β-aminoisobutyric acid, which can enter various metabolic pathways.

Structure

Dihydropyrimidinase is a metalloenzyme that requires a divalent metal ion, typically zinc or cobalt, for its catalytic activity. The enzyme is a homotetramer, meaning it consists of four identical subunits. Each subunit contains a metal-binding site that is essential for its enzymatic function.

Genetic Information

The gene encoding dihydropyrimidinase in humans is known as DPYS. Mutations in the DPYS gene can lead to a rare metabolic disorder known as dihydropyrimidinase deficiency. This condition is characterized by the accumulation of dihydropyrimidines in the urine and can result in neurological and developmental abnormalities.

Clinical Significance

Dihydropyrimidinase deficiency is an autosomal recessive disorder that can present with a variety of symptoms, including developmental delay, seizures, and intellectual disability. Diagnosis is typically made through the detection of elevated levels of dihydropyrimidines in the urine and confirmed by genetic testing.

Related Enzymes

Dihydropyrimidinase is part of a family of enzymes involved in pyrimidine metabolism. Other related enzymes include dihydropyrimidine dehydrogenase and β-ureidopropionase, which catalyze different steps in the degradation of pyrimidine bases.

Research and Applications

Research on dihydropyrimidinase has implications for understanding metabolic disorders and developing potential treatments. The enzyme is also of interest in the field of biotechnology for its potential use in the bioremediation of pyrimidine-based pollutants.

See Also

• Pyrimidine metabolism
• Dihydropyrimidine dehydrogenase
• β-ureidopropionase
• Metalloenzyme
• DPYS