Clinical implications of dihydropyrimidine dehydrogenase inhibition.

Effects of uridine and thymidine on the degradation of 5-fluorouracil, uracil, and thymine by rat liver dihydropyrimidine dehydrogenase.

The kinetic properties and control mechanisms of 5-fluorouracil (5-FU), uracil, and thymine degradation by rat liver dihydropyrimidine dehydrogenase were studied in vitro. The calculated Michaelis constant (Km) for 5-FU was 3.49 +/- 0.41 (SE) microM, similar to those for uracil (2.26 +/- 0.28 microM) and for thymine (2.23 +/- 0.34 microM). However, the reduction of 5-FU appears to be most sensi...

5-Fluorouracil toxicity and dihydropyrimidine dehydrogenase enzyme: implications for practice.

5-fluorouracil (5-FU) is a fluorinated pyrimidine analog, which is commonly used in combination chemotherapy for treating solid tumors. Dihydropyrimidine dehydrogenase plays an important role in catabolism and clearance of 5-FU. Any alteration in that sequence of enzymatic activity can lead to toxicity and even death in some patients. The most common loss of a functional allele of the dihydropy...

5-FU multifocal inflammatory leukoencephalopathy and dihydropyrimidine dehydrogenase deficiency

inflammatory leukoencephalopathy and dihydropyrimidine dehydrogenase deficiency Article abstract—Multifocal inflammatory leukoencephalopathy (MIL) is a cerebral demyelinating syndrome that develops after chemotherapy with 5-fluorouracil (5-FU) and levamisole. The authors report a patient who developed MIL after 5-FU administration not in association with levamisole. She was subsequently diagnos...

Inhibition of rat dihydropyrimidine dehydrogenase by 5-cyanouracil in vitro.

The Effects of Pyruvate Dehydrogenase Kinase 4 (PDK4) Inhibition on Metabolic Flexibility during Endurance Training in Skeletal Muscles of Streptozotocin-induced Diabetic Rats

Background:Metabolic flexibility is the capacity of a system to adjust fuel (primarily glucose and fatty acids) oxidation based on nutrient availability. Pyruvate Dehydrogenase Kinase 4 (PDK4) is one of the main enzymes that play a critical role in metabolic flexibility. In current study, we examined PDK4 inhibition along with exercise training (ET) on the gene expression of Es...