Purine methylation

Deficiency of thiopurine S-methyl transferase (TPMT) is another phenotype that exhibits inter-ethnic differences in frequency. TPMT is an enzyme that catalyzes methylation of therapeutic agents used in the treatment of acute lymphoblastic leukemia, rheumatoid arthritis, and autoimmune/inflammatory diseases, as well as in organ transplantation. Patients who have TPMT deficiency experience less efficient methylation and are at greater risk of fatal toxicity when treated with standard doses of fhiopurines. TPMT phenotype is defined by erythrocyte 6-mercapto-purine methylation. African American populations exhibit a 20% lower erythrocyte TPMT than Caucasian Americans, and persons of Chinese descent tend to exhibit greater activity than either of these other American subpopulations. 

In addition to C8 alkylation, C2 alkylation of purines has been reported. The regioselectivity has been correlated with the site of cation formation, alkylation occurring mostly on the carbon where the proton resonates at lowest field. Details of methylation products and product ratios at different pH values for a series of free-radical, purine methylations are given in Table 41. "... 

Folic Acid Deficiency. It is obvious that folic acid is a very important vitamin for biosynthetic reactions, particularly those required for the biosynthesis of purines, methyl-... 

Comparatively little information is available concerning purine methyl groups, but it seems ° that then-reactivity is comparable to pyridine a- and y-methyl substituents, undergoing base-catalysed condensations and selenium dioxide oxidation to aldehydes. 

Purines Methylated purines, purine antibiotics, pteridines, benzopteridines, pynolopyrimi-dines. 

Fia. 3. Cyanocobslainin in relation to Ci transfer in its own biosynthesis. Methyls marked with an asterisk are derived from active methyl. In the pseudo Bn the dimethylbenzimidazole moiety is replaced by purines, methyl purines, or other heterocycles. Factor B is the pigmented moiety, lacking the benzimidazole-containing nucleotide it is active for Escherichia eoli 113-3. 

Table 28 2 doesn t include all of the nucleoside components of nucleic acids The presence of methyl groups on pyrimidine and purine rings is a common and often important variation on the general theme... 

The pathways for thiamine biosynthesis have been elucidated only partiy. Thiamine pyrophosphate is made universally from the precursors 4-amino-5-hydroxymethyl-2-methylpytimidinepyrophosphate [841-01-0] (47) and 4-methyl-5-(2-hydroxyethyl)thiazolephosphate [3269-79-2] (48), but there appear to be different pathways ia the eadier steps. In bacteria, the early steps of the pyrimidine biosynthesis are same as those of purine nucleotide biosynthesis, 5-Aminoimidazole ribotide [41535-66-4] (AIR) (49) appears to be the sole and last common iatermediate ultimately the elements are suppHed by glycine, formate, and ribose. AIR is rearranged in a complex manner to the pyrimidine by an as-yet undetermined mechanism. In yeasts, the pathway to the pyrimidine is less well understood and maybe different (74—83) (Fig. 9). 

Mechanistic aspects of the action of folate-requiring enzymes involve one-carbon unit transfer at the oxidation level of formaldehyde, formate and methyl (78ACR314, 8OMI2I6OO) and are exemplified in pyrimidine and purine biosynthesis. A more complex mechanism has to be suggested for the methyl transfer from 5-methyl-THF (322) to homocysteine, since this transmethylation reaction is cobalamine-dependent to form methionine in E. coli. 

Purine, 1,6-dihydro-8,9-dimethyl-6-thioxo-synthesis, 5, 583 Purine, 2,6-dimethoxy-synthesis, 5, 596 Purine, 2,6-dimethoxy-7-methyl-rearrangement, 5, 558 Purine, 2,7-dimethyl-halogenation, 5, 547 Purine, 7,9-dimethyl-UV spectra, 5, 517 Purine, 8,8-dimethyl-synthesis, 5, 580 Purine, 6-dimethylamino-mass spectra, 5, 519 occurrence, 5, 600 Purine, 6-dimethylamino-9-benzyl-alkylation, 5, 531 Purine, 3,7-dimethyl-6,8-dioxo-methylation, 5, 534 Purine, 6,8-dioxo-alkylation, 5, 534... 

Purine, 6,8-dioxo-1,6,7,8-tetrahydro-methylation, 5, 534 synthesis, 5, 596 thiation, 5, 557... 

Purine, 2,6-dithioxo-1,2,3,6-tetrahydro-dethiation, 5, 558 Purine, 8-ethoxy-synthesis, 5, 577, 596 Purine, 6-ethoxycarbonylmethyl-nucleoside synthesis, 5, 561 Purine, 8-ethoxy-7-methyl-synthesis, 5, 577 Purine, 9-ethyl-synthesis, 5, 593 Purine, 6-fonnyl-reactions, 5, 547 synthesis, 5, 593 Purine, 8-fonnyl-reactions, 5, 547 Purine, 2-fluoro-synthesis, 5, 597 Purine, 6-fluoro-alkylation, 5, 529 synthesis, 5, 563, 573 Purine, 6-fluoro-9-methyl-reactions, with ammonia, 5, 562 Purine, 6-furfurylamino- — see Kinetin Purine, 9-glycofuranosyl-synthesis, 5, 572 Purine, 2-glycosyl-synthesis, 5, 587 Purine, 8-glycosyl-synthesis, 5, 585 Purine, 9-glycosyl-synthesis, 5, 572 Purine, 8-halo-synthesis, 5, 598 Purine, 2-hydrazino-synthesis, 5, 593 Purine, 8-o -hydroxyethyl-synthesis, 5, 574... 

NMR, 5, 513 UV spectra, 5, 517 Purine, 8-methoxy-UV spectra, 5, 517 Purine, 6-methoxy-3-methyl-hydrolysis, 5, 558 irradiation, 5, 543... 

Purine, 6-methoxy-9-methyl-hydrolysis, 5, 558 Purine, 1-methyl- H NMR, 5, 511 synthesis, 5, 594 Purine, 2-methyl-amination, 5, 542 mass spectra, 5, 519 synthesis, 5, 593 Purine, 3-methyl- H NMR, 5, 511 occurrence, 5, 598 synthesis, 5, 586, 595 Purine, 6-methyl-amination, 5, 542 mass spectra, 5, 519 methylation, 5, 529 oxidation, 5, 539 1-oxide... 

Purine, 9-methyl-6-methylamino-synthesis, 5, 570 Purine, 3-methyl-6-methylthio-irradiation, 5, 543 synthesis, 5, 535, 595... 

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