5- Aminoimidazole ribotide

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). 

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... 

A new intermediate in purine nucleotide de novo biosynthesis in E. coli, namely 7V(5)-carboxy-aminoimidazole ribotide (35) has been identified together with two new enzymatic activities involving the carboxylation of the 5-amino group of 5-aminoimidazole ribotide (AIR) and the rearrangement of the /V-carboxy derivative to the C-carboxy derivative (CAIR) (Scheme 21) <94B2269>. 

Fig. 15-16 The de novo purine biosynthetic pathway. Rib-5-P, ribose 5-phosphate P-Rib-PP, 5-phosphoribosyl 1-pyrophosphate PRA, 5-phosphoribosylamine IO-CHO-FH4, /Vl0-formyl tetrahydrofolate GAR, glycineamide ribotide FGAR. /V-formylglycineamide ribotide FGAM, /V-formylglycineamidine ribotide AIR, 5-aminoimidazole ribotide CAIR, 4-carboxy-5-aminoimidazole ribotide SAICAR, iV-succino-5-aminoimidazole-4-carboxamide ribotide AICAR, 5-aminoimidazole-4-carboxamide ribotide FAICAR, 5-formamidoimidazole-4-carboxamide ribotide sAMP, /V-succino-AMP. Enzymes (1) amido phosphoribosyltransferase (2) GAR synthetase (3) GAR transformylase (4) FGAM synthetase (5) AIR synthetase (6) AIR carboxylase (7) SAICAR synthetase (8) adenylosuecinase (9) AICAR transformylase (10) IMP cyclohydrolase (11) sAMP synthetase (12) adenylosuecinasc (13) IMP dehydrogenase (14) GMP synthetase.

In bacteria, the pyrimidine precursor 38 is derived from 5-aminoimidazole ribotide (37), an intermediate of the basic branch of purine biosynthesis, which supplies all carbon atoms for 38 by a complex rearrangement reaction (the fate of the individual carbon atoms is indicated by Greek letters in Fig. 4). In yeasts, a totally unrelated reaction sequence uses carbon atoms from vitamin Be (39) that are indicated by roman letters in Fig. 4 for the assembly of the thiamine precursor 38,... 

In plants, little is known about the basic building blocks and the reactions involved in thiamine biosynthesis. An early study with chloroplasts of spinach indicated that 1-deoxy-D-xylulose 5-phosphate, tyrosine, and cysteine act as precursors of the thiazole moiety in analogy to the pathway in E. coli. More recently, it has been shown that a homolog of the THIC protein that converts 5-aminoimidazole ribotide into 38 is essential (25). These results suggest that the plant pathway is similar to the pathway in prokaryotes but not to that in yeast. 

As noted in Scheme 12.87, the early stages of purine biosynthesis involve the generation of 5-aminoimidazole ribotide [5-amino-2-(5 -phosphoribosyl)imidazole]. In vertebrates, carboxylation of 5-aminoimidazole ribotide (Scheme 12.96) is effected with carbon dioxide (CO2) under the influence of phosphoribosylaminoimidazole... 

Then as shown in Scheme 13.67 (a reproduction of Scheme 12.96), 5-aminoimidazole ribose 5-phosphate is carboxylated (either with CO2 or with bicarbonate) to 5-carboxyamino-l-(5 -phosphoribosyl)imidazole, which rearranges to 5-aminoimidazole ribotide-4-carboxylate, and the latter undergoes amination from aspartate (Asp, D) to yield 5-amino-l-(5-phosphoribosyl)imidazole-4-carboxamide after the loss of fumarate. Finally (Scheme 13.8), A-formylation is effected with lO-CHO-H, folate to yield the A-formyl derivative (5-formamido-l-(5 -phosphoribosyl)imidaz-ole-4-carboxyamide) and cyclization yields inosine 5 -phosphate (IMP). 

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