Explain De Novo Synthesis of UMP. Describe the Steps
Uridine monophosphate (UMP) is a pyrimidine nucleotide that plays a fundamental role in RNA synthesis. In cells, UMP can be synthesized by the de novo pathway from basic precursor molecules including glutamine, aspartate, and bicarbonate. This pathway does not require preformed bases but builds the pyrimidine ring first before attaching it to the ribose sugar.
Steps in De Novo Synthesis of UMP
- Formation of Carbamoyl Phosphate:
- Catalyzed by carbamoyl phosphate synthetase II (CPS II)
- Utilizes glutamine, CO₂, and 2 ATP in the cytoplasm
- Formation of Carbamoyl Aspartate:
- Carbamoyl phosphate reacts with aspartate via aspartate transcarbamoylase
- Cyclization to Dihydroorotate:
- Carbamoyl aspartate undergoes ring closure catalyzed by dihydroorotase
- Oxidation to Orotate:
- Dihydroorotate is oxidized to orotate by dihydroorotate dehydrogenase (occurs in mitochondria)
- Formation of Orotidine Monophosphate (OMP):
- Orotate is transferred to phosphoribosyl pyrophosphate (PRPP) by orotate phosphoribosyltransferase
- Decarboxylation to UMP:
- OMP is decarboxylated to UMP by orotidine-5′-phosphate decarboxylase
Regulation
- CPS II is the rate-limiting enzyme
- UMP and other pyrimidine nucleotides feedback inhibit CPS II
This multi-step process ensures a continuous supply of UMP for RNA synthesis and other cellular processes.