Purine precursors

The pyrimidine portion of thiamin (Fig. 25-21) is distinct in structure from the pyrimidines of nucleic acids. In bacteria it originates from the purine precursor 5-aminoimidazole ribotide, which is converted into a hydroxymethylpyrimidine (Fig. 25-21 )373 which is... 

Sanchez RA, Ferris JP, Orgel LE. Studies in prebiotic synthesis. II. Synthesis of purine precursors and amino acids from aqueous hydrogen cyanide. J. Mol. Biol. 1967 30 223-253. 

The one-carbon groups carried by FH4 are transferred to dUMP to form dTMP to glycine to form serine to purine precursors to form C2 and C8 of the purine ring and to vitamin B12. 

Formate lV10-Formyl Purine precursor Purine (C2)... 

Histidine (via formiminoglutamate) V5,1V10-Methenyl (A, Af1(,-Methylidyne) Purine precursor Purine (C8)... 

The entire glycine molecule is added to the growing purine precursor. Then C8 is added by methenyl tetrahydrofolate, N3 by glutamine, C6 by C02, N1 by aspartate, and C2 by formyl tetrahydrofolate (see Figure 7-20, bottom). 

Using nucleosides as reference metabolites - Structure of the purine precursor of... 

A biosynthetic relationship between purines and flavin had been initially conjectured on the basis of fermentation experiments where the addition of certain purine derivatives increased the yield of riboflavin produced by flavinogenic microorganisms. Ample confirmation for that hypothesis was obtained by isotope incorporation studies performed in parallel by various research groups using different microorganisms. Specifically, it was shown that the pyrimidine ring of purines can be contributed to biosynthetic riboflavin in its entirety, whereas C-8 of the imidazole ring of purine precursors is lost. The early work has been reviewed repeatedly and will not be discussed in detail. ... 

Studies with purine-deficient mutants narrowed the purine precursor down to a compound at the biosynthetic level of guanine. This implicated that the amino group of the cognate guanine precursor had to be replaced by oxygen in the course of biosynthesis. 

Conditions causing hyperuricemia include the excessive synthesis of uric acid, the excessive synthesis of purine— precursor to uric acid—a high dietary intake of purine (shellfish, organ meat, anchovies, and wild game), diminished renal excretion of uric acid, and tissue destruction following injury or therapeutic irradiation. 

Fig. 41.5. Incorporation of glycine into the purine precursor. The ATP is required for the condensation of the glycine carboxylic acid group with the F-amino group of phosphoribosyl 1-amine.

The biosynthesis of uric acid from the immediate purine precursor xanthine that results from adenine, via the intermediate hypoxanthine, or from guanine is illustrated in Figure 36.32. The enzyme xanthine oxidase (a molybdenum hydroxylase enzyme) is involved in two steps, the conversion of hypoxanthine to xanthine, and the final step, the conversion of xanthine to uric acid. Allopurinol originally was designed... 

The importance of the avian liver in the synthesis of uric acid became dear as the result of two early experiments (see Baldwin, 1967). When geese were hepatectomised, there was a rapid rise in the concentration of ammonia in the blood and when goose liver was perfused with ammonia, the formation of uric acid could be detected. The biosynthetic pathway leading to uric add formation shares many of the enzymes required for the purine precursors of the purine nucleotides. The three steps that are distinct for uric acid formation are the conversion of... 

Biosynthesis The biosynthesis of R. from purine precursors (especially guanosine) occurs only in plants and microorganisms, humans and animals are not able... 

Inosinic acid as purine precursor, IX, 87 Inositol, VI, 196, 226, 270 absorption by yeast, VI, 197 bioassay, VIII, 148... 

Thus, early studies involved radiotracer experiments that established the outlines of the biosynthetic steps leading to toyocamycin and sangivamycin in which the deazapurine base was shown to be derived from a purine precursor through a process parallel to transformations involved in the formation of folate and riboflavin (Figure 5.30) [111, 112]. When [2- " C]- or [8- " C]-labeled adenine and guanine were fed to Streptomyces rimosus cells in culture, the isolated toyocamycin retained the label at carbon-2 but lost it at carbon-6. Interestingly, the carbons 5 and 6 of the pyrrole moiety as well as the cyano carbon appeared to derive from the C-1, C-2, and C-3 of the proffered ribose, respectively. Although at that time the exact... 

The major attention was devoted to the use of orotic acid, its inorganic salts and organic derivatives for the treatment of chronic and virus hepatitis [482-489] and other forms of liver insufficiency [490-492]. The beneficial effect of orotic acid and other pyrimidine (and purine) precursors of nucleic acids in the liver led to the appearance of several preparations containing orotic acid in combination with vitamins and other components which were used during the treatment of liver insufficiency. There is a number of clinical and experimental data obtained by Wildhirt [489, 496-498], Nieper [441-443], and others [499-506] which show the beneficial role of orotic acid during the treatment of various liver diseases and speak in favour of its therapeutic use. 

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