sentences:  The loop opening happens in two-steps with the PRPP dissociation unfavorable and slow since the loop closes 85% of the time.Three key pyrimidine nucleosides include uridine, cytidine and thymidine, and they play major roles in nucleic acid biosynthesis as well as carbohydrate and lipid metabolism.Pyrimidine phosphoribosyltransferases such as orotate phosphoribosyltransferase activate their substrates by forming SN1-like transition states, facilitating migration of the ribosyl anomeric carbon region to MgPPi.