Uridine 5’-monophosphate UMP

A. The pyrimidine ring is synthesized first and is then attached to ribose 5- ph os-phate to eventually produce the nucleotide uridine 5 -monophosphate (UMP). 

The common pyrimidine ribonucleotides are cytidine 5 -monophosphate (CMP cytidylate) and uridine 5 -monophosphate (UMP uridylate), which contain the pyrimidines cytosine and uracil. De novo pyrimidine nucleotide biosynthesis (Fig. 22-36) proceeds in a somewhat different manner from purine nucleotide synthesis the six-membered pyrimidine ring is made first and then attached to ribose 5-phosphate. Required in this process is carbamoyl phosphate, also an intermediate in the urea cycle (see Fig. 18-10). However, as we noted... 

The last two steps in the biosynthesis of the mononu- cl cotide uridine 5 -monophosphate (UMP) are catalyzed by (1) orotate phosphoribosyltransferase (OPRTase) and (2) orotate 5 -monophosphate decarboxylase (OMPDase). 

De novo pathway of uridine-5 -monophosphate (UMP) synthesis. Enzymes (1) carbamoyl phosphate synthetase II (2) aspartate transcarbamoylase (3) dihydroorotase (4) dihydroorotate dehydrogenase (5) orotate phosphoribosyltransferase (6) orotidine-5 -monophosphate decarboxylase (orotidylate decarboxyla.se). 

Reaction of aspartic acid (14) with carbamoyl phosphoric acid (17) in the presence of the allosteric enzyme aspartate carbamoyltransferase (aspartate transcar-bamoylase) gives N-carbamoyl aspartic acid (18), which is cyclised to L-dihy-droorotic acid (19) by dihydroorotase. Oxidation of L-dihydroorotic acid by flavoprotein, orotate reductase gives orotic acid (20), which reacts with 5-phosphori-bosy 1-1-pyrophosphate (PRPP) in the presence of orotate phosphoribosyl transferase to form orotidine 5 -monophosphate (OMP, 21). Decarboxylation of OMP by orotid-ine 5 -phosphate decarboxylase yields uridine 5 -monophosphate (UMP, 22), which acts as precursor for the cytidine nucleotides (CTP) (Chart 6). 

Uridylic Acid. Uridine 5 -phosphoric acid uridine 5 -monophosphate UMP. C,H,2N20,P mol wt 324.19, C 33.34%, H 4.047=, N 8.64%, O 44.42%, P 9.56%-. Nucleotide widely distributed in nature. Synthesis by phos, phorylation of 2, 3 -O-benzylidene uridine with diphenyl phosphorochloridate Brown et aL, J. Chem. Soc. 1950, 408 Smith, Biochem. Prepn. 8, 130 (i960. Monograph on the synthesis of nucleotides G. R Pettit, Synthetic Nucleotides vol. 1 (Van Nostrand Reinhold, New York, 1972) 252 pp. Crystal structure of hydtated barium salt Shelter, True-blood, Acta Cryst. 18, 1067 (1965). Reviews see Uridine Nucleic Acids. 

A new chemoenzymatic synthesis of UDP-GalNAc consists of a multi-enzyme catalyzed generation of UDP-galactosamine from uridine-5 monophosphate (UMP) and sucrose in a repetitive batch mode, followed by a chemical acetylation step [164],... 

The mechanism of the enzymatic decarboxylation of orotidine 5 -mono-phosphate (OMP) to uridine 5 -monophosphate (UMP) (see Fig. 1) is an intriguing problem for which many solutions have been offered. Even before 1995 when Wolfenden and Radzicka declared OMP decarboxylase (ODCase) to be the most proficient enzyme [1], several different mechanisms had been proposed. Since that time, other mechanisms have been advocated. Curiously, the appearance of crystal structures for various wild-type and mutant ODCases has led not to a definitive picture of catalysis, but to even more conjecture and controversy concerning the mechanism. 

The first step in de novo pyrimidine biosynthesis is the synthesis of carbamoyl phosphate from bicarbonate and ammonia in a multistep process, requiring the cleavage of two molecules of ATP. This reaction is catalyzed by carbamoyl phosphate synthetase (CPS), and the bicarbonate is phosphorylated by ATP to form carboxyphosphate and ADP (adenine dinucleotide phosphate). Ammonia then reacts with carboxyphosphate to form carbamic acid. The latter is phosphorylated by another molecule of ATP with the mediation of CPS to form carbamoyl phosphate, which reacts with aspartate by aspartate transcarbamoy-lase to form A-carbamoylaspartate. The latter cyclizes to form dihydroorotate, which is then oxidized by NAD-1- to generate orotate. Reaction of orotate with 5-phosphoribosyl-l-pyrophosphate (PRPP), catalyzed by pyrimidine PT, forms the pyrimidine nucleotide orotidylate. This reaction is driven by the hydrolysis of pyrophosphate. Decarboxylatin of orotidylate, catalyzed by orotidylate decarboxylase, forms uridylate (uridine-5 -monophosphate, UMP), a major pyrimidine nucleotide that is a precursor of RNA (Figure 6.53). 

Uridine 5 -monophosphate. UMP. Uridines -phosphoric acid. Uridine 5-phosphate [58-97-9]... 

The final steps of pyrimidine biosynthesis novo which are catalyzed by two sequential enzymes, orotate phosphoribosyltransfer-ase (OPRT) and orotidylic decarboxylase (ODC), involve the PP-ribose P dependent conversion of orotic acid to orotidine-5 -monophosphate (OMP) followed by decarboxylation at the 7 position to form uridine 5 -monophosphate (UMP) (Fig. 1). UMP is then utilized further in the synthesis of nucleic acids and co-enzymes. Defects at this site in this metabolic pathway are important for they can result in "pyrimidine starvation" from depletion of the intracellular pool of pyrimidine nucleotides. In man the rare genetic disease, orotic aciduria, involves a deficiency of both OPRT and ODC (Type 1) (Smith, Sullivan and Huguley, 1961) or, less commonly, only ODC (Type II) (Fox, 0 Sullivan and Firken, 1969). 

The formation of uridine 5 -monophosphate (UMP) (aheady shown, in part, in Schemes 9.98 and 12.7) is shown in greater detail in Scheme 14.8. 

Scheme 14.8. A representation of a pathway to uridine 5 -monophosphate (UMP). EC numbers and some graphic materials in this scheme have been taken from appropriate links in a URL starting with http //www.chem.qmul.ac.uk/iubmb/enzyme.

FIGURE 28.5 Typical chromatogram for separation of five nucleotides by ion-pair reversed-phase HPLC method. (1) cytidine 5 -monophosphate (CMP) (2) uridine 5 -monophosphate (UMP) (3) guanosine 5 -monophosphate (GMP) (4) inosine 5 -mono-phosphate (IMP) (5) adenosine 5 -monophosphate (AMP). The concentration of each nucleotide injected onto the column was 15 mg L h (Reprinted from Food Chem., 7A, Ferreira, I. M. P. L. V. O. et al., The determination and distribution of nucleotides in dairy products using HPLC and diode-array detection, 239-244, Copyright 2001, with permission from Elsevier.)... 

FIG, 1. Proposed mechanism of action of pyrazofurin (PF) converted into the 5 -monophosphate (PFMP) in cells, the drug inhibits the conversion of orotidine 5 -monophosphate (OMP) to uridine 5 -monophosphate (UMP). Other abbreviations are CA-carbamylaspartase, DHOA-dihydroorotic acid, OA-orotic acid, PRPP-5 -phosphoribosyl pyrophosphate, PP-pyrophosphoric acid, UDP--uridine diphosphate, CTP-cytidine triphosphate, RNA-ribonucleate, DNA-deoxyribonucleate,... 

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