Gene Expression of Enzymes Required for the De Novo Synthesis and Degradation of Pyrimidines in Rat Peripheral Tissues and Brain

Abstract

Tissue-specific expression of the genes coding for the six enzymes of the de novo pyrimidine synthesis and for the first enzyme of the degradation pathway, dihydropyrimidine dehydrogenase (DPD), was analyzed in the rat using the in situ hybridization technique. Transcripts of the biosynthetic enzymes were detected in liver, kidney, and spleen with the highest expression in the white pulp. DPD was also transcribed in these organs with a striking layer-specific localization of DPD mRNA and protein in the kidney. All enzyme mRNAs were present in brain at low levels, but with region- and cell-specific differences. The relatively high expression in cortical regions including cerebellum and hippocampus points to a fundamental role of pyrimidine metabolism in brain function.

Keywords:

• CAD
• dihydroorotate dehydrogenase
• dihydropyrimidine dehydrogenase
• gene expression
• uridine monophosphate synthase

Acknowledgments

We thank U. Beck, B. Kowalski, B. Wiegand, and M. Schneider for expert technical assistance, and E. Weihe for critical comments. This study was supported by the Faculty of Medicine of the Philipps-University Marburg.