Ribotides

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 first pharmacological agent shown to activate AMPK was 5-aminoimidazole-4-carboxamide (AICA) riboside, also known as acadesine. This adenosine analogue is taken up into cells by adenosine transporters and phosphoiylated by adenosine kinase to the mono-phosphorylated form, AICA ribotide or ZMP. ZMP accumulates inside cells to higher concentrations than the concentration of AICA riboside present in the medium, and it mimics both effects of AMP on AMPK system (allosteric activation and inhibition of... 

Henceforward, the chapter focuses on problems closely connected with the chemistry of ribonucleotide 46 and ribonucleoside 47. The official numbering of the atoms in these molecules is recalled in formulas 46, 47. The common abbreviations, AIR and AIRs respectively, are used for the ribotide and the riboside. 

A component of the ribotide reductase complex of enzymes, protein Ba, has been shown to contain two non-heme iron atoms per mole (77). This enzyme plays a vital, albeit indirect, role in the synthesis of DNA. Curiously, the lactic acid bacteria do not employ iron for the reduction of the 2 hydroxyl group of ribonucleotides. In these organisms this role has been assumed by the cobalt-containing vitamin Bi2 coenzyme (18). The mechanism of the reaction has been studied and has been shown to procede with retention of configuration (19). 

Ribotide reductase protein Ba E. coti, animal tissues... 

The hemerythrin of Golfingia gouldii consists of eight subunits, each of which contains two iron atoms, in a protein with molecular weight 108,000. Spectral and magnetic data point to an oxo-bridged structure around the non-heme iron atom (99). Protein B2 of ribotide reductase of E. coli has some properties in common with hemerythrin presumably a protein corresponding to that of E. coli reduces ribotides in animal tissues, a conclusion based on probes with inhibitors. 

Biosynthesis is performed in one step by the enzyme L-histidine decarboxylase (HDC, E.C. 4.1.1.22). Histamine metabolism occurs mainly by two pathways. Oxidation is carried out by diamine oxidase (DAO, E.C. 1.4.3.6), leading to imidazole acetic acid (IAA), whereas methyla-tion is effected by histamine N-methyltransferase (HMT, E.C. 2.1.1.8), producing fe/e-methylhistamine (t-MH). IAA can exist as a riboside or ribotide conjugate. t-MH is further metabolized by monoamine oxidase (MAO)-B, producing fe/e-methylimidazole acetic acid (t-MIAA). Note that histamine is a substrate for DAO but not for MAO. Aldehyde intermediates, formed by the oxidation of both histamine and t-MH, are thought to be quickly oxidized to acids under normal circumstances. In the vertebrate CNS, histamine is almost exclusively methylated... 

Mutations in the gene for adenylosuccinate lyase (ASL), inherited as an autosomal recessive disorder in purine metabolism, are associated with severe mental retardation and autistic behavior, but apparently not self-mutilation [10, 11]. This enzyme catalyzes two distinct reactions in the de novo biosynthesis of purines the cleavages of adenylosuccinate (S-Ado) and succinylaminoimidazole carboxamide ribotide (SAICAR), both of which accumulate in plasma, urine and cerebrospinal fluid of affected individuals [12]. Measurements of these metabolites in urine... 

PIP2 phosphatidylinositol 4,5-bisphosphate SAICAR succinylaminoimidazole carboxamide ribotide... 

Equation 1 is catalyzed by glycinamide ribotide (GAR) trans-formylase and Equation 2 is catalyzed by aminoimidazole-carboxamide ribotide (AICAR) transformylase. 

Formamidine sulfinic acid, for bleaching of recycled pulps, 21 52 9-Formamido-mino, 24 598 Formaminoimidazole carboxamide ribotide (FAICAR)... 

Formyl fluoride (HCOF), 12 178-179 Formylglycine ribotide (FGAR), folic acid and, 25 802... 

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... 

The biosynthesis of histidine. The 5-aminoimidazole-4-carboxamide ribotide formed during the course of histidine biosynthesis is also an intermediate in purine nucleotide biosynthesis. Therefore it can be readily regenerated to an ATP, thus replenishing the ATP consumed in the first step in the histidine biosynthetic pathway (see fig. 23.13). 

Phosphoribosyl formimino-5-aminoimidazole-4-oarboxamide ribotide isomerase v... 

Application of Prep-HPLC to PGS Analysis. Reverse phase liquid chromatography has proven to be well suited for cleanup of plant extracts by prep-HPLC (4, 46, 47, 48). When the mobile phase is initially an aqueous buffer at pH 2.8, all but the highly charged (e.g., zeatin ribotide with 5 AMP used as a representative compound for zeatin ribotide) plant hormones are retained at the head of the column (Fig. 1). Since the PGS are retained, samples can be injected onto the column in a dilute form. In-... 

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>. 

Although there are a number of inefficient steps in most proposed prebiotic syntheses of ribotides, the major objection to RNA as the primogenitor of life has been the relatively small yield of ribose in the formose reaction, a simple condensation of glycoaldehyde. Muller et a/.,18 however, have discovered a variation of the formose reaction that produces a limited mix of pentose diphosphates in which the ribose forms predominate (52 14 23 11, ribose arabinose lyxose xylose). Although many critical chemical roadblocks remain (such as the extremely low yield of pyrimidine nucleosides following the condensation of ribose and free bases), this advance belies the previously held view that products of the formose reaction are necessarily so chemically diverse that they are the carbohydrate analog of petroleum. 19... 

So far, we have constructed an unsatisfying picture of the earliest days of an RNA world although some prebiotic mechanisms may exist for the untemplated formation of oligonucleotides, these molecules would have been short, would have contained a variety of monomers besides ribotides, and could not have been faithfully copied by the template-directed polymerization of monomers. Given this model, it is difficult to imagine the accumulation of RNA sequences necessary for the Darwinian selection of a multitude of active ribozymes. Nevertheless, these precursors may have been adequate for the first critical step in the formation of life the formation of an RNA replicase. 

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.

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