Uridine-5-phosphate

Sodium uridine-5 -phosphate 224 is converted by HMDS 2/TCS 14 and pyrroh-dine at 145 °C, via the assumed persilylated intermediate 225, and after transsilyla-tion with boiling methanol and addition of NaOH, crystalline sodium-cytidine-5 -phosphate 226 in 69% yield [49] (Scheme 4.19). 

On silylation-amination of the disodium salts of inosine-5 -phosphate 238a or of guanosine-5 -phosphate 238 b with benzylamine, the phosphate moieties are also transiently protected during amination by silylation (cf also the silylation of uridine-5 -phosphate 224) to give, after transsilylation with methanol and addition of NaOH, the desired sodium salt of N -benzyladenosine-5 -phosphate 239a in 80% yield and the sodium salt of the 2-amino derivative 239 b in 78% yield [64] (Scheme 4.23). 

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).

Orotic acid in the diet (usually at a concentration of 1 per cent) can induce a deficiency of adenine and pyridine nucleotides in rat liver (but not in mouse or chick liver). The consequence is to inhibit secretion of lipoprotein into the blood, followed by the depression of plasma lipids, then in the accumulation of triglycerides and cholesterol in the liver (fatty liver) [141 — 161], This effect is not prevented by folic acid, vitamin B12, choline, methionine or inositol [141, 144], but can be prevented or rapidly reversed by the addition of a small amount of adenine to the diets [146, 147, 149, 152, 162]. The action of orotic acid can also be inhibited by calcium lactate in combination with lactose [163]. It was originally believed that the adenine deficiency produced by orotic acid was caused by an inhibition of the reaction of PRPP with glutamine in the de novo purine synthesis, since large amounts of PRPP are utilized for the conversion of orotic acid to uridine-5 -phosphate. However, incorporation studies of glycine-1- C in livers of orotic acid-fed rats revealed that the inhibition is caused rather by a depletion of the PRPP available for reaction with glutamine than by an effect on the condensation itself [160]. 

Fermentation procedures useful for the production of uridine 5 -(a-D-galactopyranosyl pyrophosphate) involve the cultivation of bacterial mutant-strains that are deficient in the 4"-epimerase for 30 (see Section V,l,b, p. 369) in D-galactose-containing media,245-247 or by incubating Torulopsis Candida cells with uridine 5 -phosphate, D-galactose, potassium phosphate, and magnesium sulfate.248... 

Fermentation procedures for preparing uridine 5 -(2-acetamido-2-deoxy-a-D-glucopyranosyl pyrophosphate) have also been reported. One of them255 involves the cultivation of Helminthosporium sativum in the presence of 2-amino-2-deoxy-D-glucose and the antibiotic polyoxin the latter is an inhibitor of chitin biosynthesis. The other256 utilized the incubation of yeast cells with uridine 5 -phosphate in the presence of an excess of 2-amino-2-deoxy-D-glucose and inorganic phosphate.257... 

In all of the foregoing examples, an activated derivative of the nucleotide has been employed for generating the pyrophosphate link. An attempt to use an activated glycosyl phosphate failed 311 the only product identified from the reaction between /3-D-glucopyranosyl phosphoramidate (68) and uridine 5 -phosphate was the cyclic phosphate 69. The ease of participation of the sterically accessible, C-2 hydroxyl group probably accounts for this result. The usual procedure... 

Alkaline hydrolysis of uridine 5 - (a - D- glucopyranosyl pyrophosphate) results in the formation of uridine 5 -phosphate and a-D-glu-copyranose 1,2-cyclic phosphate24 (81). The reaction reaches completion after 30 min at 0° in concentrated aqueous ammonia, or after 2 min at 100° and pH 8.5. Partial conversion of the cyclic phosphate (81) into a-D-glucopyranosyl phosphate and D-glucose 2-phosphate occurs under conditions of elevated temperature. 

Uridine 5 -phosphate or 5 -pyrophosphate and 2 -deoxyuridine 5 -phosphate react with hydroxylamine approximately 1.5 times faster than the related 5 -(a-D-glucopyranosyl pyrophosphates), whereas the velocities are the same for reactions of the corresponding... 

Adenosine 5 -phosphate Guanosine 5 -phosphate Cytidine 5 -phosphate Uridine 5 -phosphate... 

UDP-apiose (5) is very unstable under a variety of conditions of pH and temperature this instability had previously prevented 7 the isolation of sufficient quantities of UDP-apiose for definitive identification. UDP-[U-l4C]apiose is degraded at pH 8.0 to uridine 5 -phosphate and 3-C-(hydroxymethyl)-a-D-[U-14C] erythrofuranosyl 1,2-phosphate at 80, 25, and 4°. The half-lives of UDP-[U-14C]apiose under these conditions are 31.6 seconds, 97.2 minutes, and 16.5 hours, respectively.7 The half-life of UDP-[U-,4C]apiose at pH 3.0 and 40° is 4.67 minutes. It is degraded7 to uridine 5 -pyrophosphate and D-[U-I4C]apiose. At pH 6.2-6.6 and 4°, degradation (of both the... 

We see that uridine 5 -phosphate (UMP) is formed from aspartate in a relatively direct and simple... 

---