Uracil/thymine dehydrogenase

Uracil/thymine dehydrogenase is an enzyme that plays a crucial role in the metabolism of nucleic acids, specifically in the catabolism of pyrimidines such as uracil and thymine. This enzyme catalyzes the conversion of uracil and thymine to dihydrouracil and dihydrothymine, respectively, in the presence of NADPH as a cofactor. This reaction is an essential step in the pyrimidine degradation pathway, which ultimately leads to the production of beta-alanine, a precursor for the synthesis of pantothenic acid (vitamin B5) and the neurotransmitter beta-aminobutyric acid.

Function

Uracil/thymine dehydrogenase is involved in the breakdown of pyrimidine nucleotides, which are one of the two classes of nucleotides found in nucleic acids. The enzyme ensures that excess pyrimidines from cellular processes or from the diet are efficiently degraded and removed from the body. This degradation is vital for maintaining the balance between the synthesis and degradation of nucleic acids, and for the recycling of pyrimidines for further nucleic acid synthesis.

Enzyme Mechanism

The enzyme operates by reducing the double bond between the C5 and C6 positions of uracil or thymine, using NADPH as a reducing agent. This reduction results in the formation of dihydrouracil or dihydrothymine, which are less toxic and more soluble, facilitating their further breakdown and eventual excretion from the body.

Clinical Significance

Alterations in the activity of uracil/thymine dehydrogenase can have significant clinical implications. Reduced activity of this enzyme can lead to an accumulation of uracil and thymine, which can be toxic to cells. This condition is associated with a rare genetic disorder known as dihydropyrimidine dehydrogenase deficiency, which can lead to severe neurological disorders and an increased risk of toxicity in patients receiving certain chemotherapeutic agents that are metabolized by this pathway.

Genetic Regulation

The gene encoding uracil/thymine dehydrogenase is regulated by various factors, including nutritional status and hormonal signals. This regulation ensures that the enzyme's activity is modulated according to the body's metabolic needs.

See Also

• Pyrimidine metabolism
• Nucleotide metabolism
• Dihydropyrimidine dehydrogenase deficiency
• NADPH