Orotidine

Orotidine Monophosphate Decarboxylase Volume Editors Lee, J.K., TantiUo, D.J. 

While mammahan cells reutilize few free pyrimidines, salvage reactions convert the ribonucleosides uridine and cytidine and the deoxyribonucleosides thymidine and deoxycytidine to their respective nucleotides. ATP-dependent phosphoryltransferases (kinases) catalyze the phosphorylation of the nucleoside diphosphates 2 "-de-oxycytidine, 2 -deoxyguanosine, and 2 -deoxyadenosine to their corresponding nucleoside triphosphates. In addition, orotate phosphoribosyltransferase (reaction 5, Figure 34-7), an enzyme of pyrimidine nucleotide synthesis, salvages orotic acid by converting it to orotidine monophosphate (OMP). 

Computational studies of alkene oxidation reactions by metal-oxo compounds, 38, 131 Computational studies on the mechanism of orotidine monophosphate decarboxylase,... 

Orbital interactions and long-range electron transfer, 38, 1 Organic materials for second-order non-linear optics, 32, 121 Organic reactivity, electron-transfer paradigm for, 35, 193 Organic reactivity, structure determination of, 35, 67 Orotidine monophosphate decarboxylase, the mechanism of, 38, 183... 

PRTase - phosphoribosyl transferase ODCase - OMP decarboxylase OMP - orotidine 5 -phosphate... 

Conditions columns, Asahipak GS320 (vinyl alcohol copolymer gel), 50 cm x 7.6 mm i.d. eluent, 0.1 M sodium phosphate containing 0.3 M sodium chloride pH 7.0 flow rate, 1 ml min-1 detection, UV 250 nm direct injection of sample. Peaks l, protein, 2, orotidine 3, creatinine, and 4, uric acid. 

Figure 8.19. Sequence reactions from aspartic acid (AA) and carbamoyl phosphate (CP) to the end product, cytidine triphosphate (CTP). The first reaction is catalyzed by ATCase. The intermediary compounds are N-carbamoyl aspartic acid (N-CAA), L-dihydroorotic acid (L-DHOA), orotic acid (OA), orotidine 5 -phosphate (0-5 -P), uridine 5 -phosphate (U-5 -P), uridine diphosphate (UDP), and uridine triphosphate (UTP).

Houk KN, Tantillo DJ, Stanton C, Hu Y (2004) What have Theory and Crystallography Revealed About the Mechanism of Catalysis by Orotidine Monophosphate Decarboxylase 238 1-22 Houseman BT, Mrksich M (2002) Model Systems for Studying Polyvalent Carbohydrate Binding Interactions. 218 1-44 Hricoviniovd Z, see Petrus L (2001) 215 15-41 Hu Y, see Houk KN (2004) 238 1-22... 

Michalski J, Dabkowski W (2003) State of the Art. Chemical Synthesis of Biophosphates and Their Analogues via P Derivatives. 232 93-144 Miller BG (2004) Insight into the Catalytic Mechanism of Orotidine 5 -Phosphate Decarboxylase fi"om Crystallography and Mutagenesis. 238 43-62 Mikolajezyk M, Balczewski P (2003) Phosphonate Chemistry and Reagents in the Synthesis of Biologically Active and Natural Products. 223 161-214 Mikolajezyk M, see Drabowicz J (2000) 208 143-176... 

Wu N, Pai EP (2004) Crystallographic Studies of Native and Mutant Orotidine 5 -Phosphate Decarboxylases. 238 23-42... 

In the case of orotic acid, nonenzymatic decarboxylation proceeds with a half-time (ti/2) of about 2.45 X 10 s near pH 7 at room temperature, as indicated by reactions in quartz tubes at elevated temperatures Orotidine 5 -phosphate decarboxylase thus appears to be an extremely proficient enzyme which enhances the reaction rate by a factor of 10 . They estimate the transition state form of the substrate has a dissociation constant that is less than 5 x 10 M. 

This enzyme [EC 2.4.2.10], also known as orotidyhc acid phosphorylase and orotidine-5 -phosphate pyrophosph-orylase, catalyzes the reaction of orotate with 5-phospho-a-D-ribose 1-diphosphate to produce orotidine 5 -phos-phate and pyrophosphate (or, diphosphate). 

This enzyme [EC 4.1.1.23], also known as orotidine-5 -phosphate decarboxylase, catalyzes the conversion of orotidine 5 -phosphate to UMP and carbon dioxide. 

OROTIDYLATE DECARBOXYLASE Orotidine-5 -phosphate decarboxylase, OROTIDYLATE DECARBOXYLASE Orotidine-5 -phosphate pyrophosphorylase,... 

The most important pyrimidine derivatives are those upon which biological organisms depend. Cytosine 1018 and uracil 1019 are found in ribonucleic acid (RNA) in the form of their ribonucleotides, cytidine 1020 and uridine 1021, while in deoxyribonucleic acid (DNA), cytosine and thymine 1022 are found in the form of their 2 -deoxyribonucleotides, 2 -deoxycytidine 1023 and thymidine 1024. 5-Methylcytosine 1025 is also found to a small extent (c. 5%) in human DNA in the form of its 2 -deoxyriboside 1026, and 5-(hydroxymethyl)cytosine-2 -deoxyriboside 1027 has also been detected in smaller amounts <2005CBI1>. Many variants of cytosine and uracil can be found in RNA including orotic acid 1028 in the form of its ribonucleotide orotidine 1029. Other pyrimidine derivatives to have been isolated from various biological sources include 2 -deoxyuridine 1030, alloxan 1031, and toxopyrimidine (pyramine) 1032 (Figure 2). 

Special assays (urine and plasma) lactate, orotidine, thiosulphate, carnitine, succinylacetone, hydroxyproline, urate, orotate, sialic acid, MPS, guanidino-acetate, HVA, pyroglutamate, 5H1AA, pipecolate, pyruvate, 3-hydroxybutyrate, phytanate, VLCFA, homocysteine, 7-dehydrocholesterol, phenylalanine ERNDIM 8 148... 

The mean recovery of 100% (range 63% for orotidine to 124% for 2,8 dihydroxy-adenine) is probably acceptable similarly, the mean intra-laboratory imprecision ( V =11.9%, range 6.0 for pseudouridine to 21.9% for succinyl adenosine) is likely to be adequate for most clinical applications. However, the interlaboratory imprecision is somewhat disturbing mean CV = 126% (range 16.8% for pseudouridine to 295% for orotidine). This variation indicates the need to harmonise standardisation. 

Orotidine monophosphate decarboxylase seems to be a reigning champion of catalytic rate enhancement by an enzyme. 

Low activities of orotidine phosphate decarboxylase and orotate phosphoribosyltransferase result in abnormal growth, megaloblastic anemia and the excretion of large amounts of orotate in the urine. 

Orotidine 5 -phosphate undergoes an unusual decarboxylation (Fig. 25-14, step/), which apparently is not assisted by any coenzyme or metal ion but is enhanced over the spontaneous decarboxylation rate 1017-fold. No covalent bond formation with the enzyme has been detected.268 It has been suggested that the enzyme stabilizes a dipolar ionic tautomer of the substrate. Decarboxylation to form an intermediate ylid would be assisted by the adjacent positive charge.269,270 Alternatively, a concerted mechanism may be assisted by a nearby lysine side chain.270a d Hereditary absence of this decarboxylase is one cause of orotic aciduria. Treatment with uridine is of some value.271... 

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