SAICAR

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... 

SAICAR synthetase SAICAR lyase AICAR transformylase (jj) IMP synthase... 

A bifunctional enzyme, comprising the activities of AIR carboxylase and SAICAR synthetase, catalyzes reactions 6 and 7 of the purine pathway (AIR—> CAIR— SAICAR Fig. 15-16). A second bifunctional enzyme, IMP synthase, containing the activities of AICAR transformylase and IMP cyclohydrolase, catalyzes reactions 9 and 10 of the pathway (AICAR — FAICAR— IMP Fig. 15-16). Human IMP synthase has a subunit molecular weight of 62.1 kDa and associates as a dimer. A... 

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.

V.M. Levdikov, V.V. Barynin, Al. Grebenko, W.R. Melik-Adamyan, V.S. Lamzin, and K.S. Wilson. 1998. The structure of SAICAR synthase An enzyme in the de novo pathway of purine nucleotide biosynthesis Structure 6 363-376. (PubMed)... 

Mbose-P 5-Aminoimidazole-4 N-succino-carboxamida ribonucleotide (SAICAR)... 

AIR carboxylase A -CAIR mutase SAICAR synthetase (9) SAICAR lyase ) AICAR transformylase (Q IMP synthase... 

Lukens, Buchanan, J. Biol Cherrt. 234, 1791 (1959). Production by adenine-requiring mutants of Bacillus sublilis Ohmura et al, UJS. pat. 3,280,007 (1966 to Takeda). Synthesis of SAICAR and derivatives Burrows, Shaw, J. 

Dibarium salt, C Hj Ba-N O P. uv max (pH I) 269, 244 nm (e 11,850, 9580). If the Bratton -Marshall procedure [J. Biol. Chem. 128, 537 (1939)] is modified by keeping the sample in ice during, and for 10 minutes after the addition of the reagents, SAICAR produces a purple chromophore having max absorption at 550 nm. The diazonium salt of SAICAR is very unstable and dec before it can couple under the usual test conditions. 

There is a fifth bifunctional enzyme that catalyzes reactions 8 and 12 of the purine pathway, but adenylosuccinate lyase has one active site with dual specificity, catalyzing both reactions (SAICAR AICAR, sAMP AMP). All 14 enzymic activities of Fig. 14-18 are cytosolic, and there is a variety of evidence for association of subsets of these activities in vivo. 

The first chemical synthesis of SAICAR (3), an intermediate in purine nucleotide biosynthesis, has been reported. The imidazole ring was elaborated around the amino group of 2,3-0-isopropylidene-P-D-ribofuranosylamine. ... 

In the area of 5 -phosphates, a chemical synthesis of SAICAR (3) has been described, along with a route to carbocyclic AMP and carbocyclic adenylosuccinate. Ferrocene has been attached, via a 5 -phosphodiester and a spacer arm, to thymidine. Subsequent attachment of a thioethanol unit, via a 3 -phosphodiester,... 

Aminoimidazole ribonucleotide (AIR) Aminoimidazolecarboxylate ribonucleotide (CAIR) Aminoimidazole succinocarboxamide ribonucleotide (SAICAR) Aminoimidazolecarboxamide ribonucleotide (AICAR) Formamidoimidazolecarboxamide ribonucleotide (FAICAR)... 

Thin-layer chromatography is no longer in use on a large scale, but may be helpful in isolated cases such as adenylosuccinase deficiency [3]. The diazo reagent not only stains with succinyl aminoimidazole carboxamide riboside (SAICAR), but also with xanthine and guanine. 

The carbocyclic analogue 118 of AICAR, an intermediate in purine nucleoside biosynthesis, has been prepared in a sequence which involved elaboration of the imidazole ring from a cyclopentylamine a similar sequence was used to make the later biosynthetic intermediate SAICAR. 

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