Arabinose 1-phosphate

The discrepancy between the behavior of arabinose- and xylose-3, 5-(hydrogen phosphates) probably reflects the difference which exists in the steric arrangement of these two cyclic phosphodiesters. In the xylo-furanose derivative (89), the hydroxyl group on C-3 and the primary hydroxyl group are cis the cyclic phosphate is easily formed and perfectly strainless. In arabinofuranose these same groups are in position trans and, although an apparently strainless molecule can be constructed from models, it is probable that in this case the main ring of the compound will be that formed by the phosphodiester, with a concomitant tendency for the compound to assume the aldehydo form. Objection to... 

Deoxy-i>maw f)-2-octulosonic acid 8-phosphate can be obtained in gram quantities by using KDO synthase (F.C 4.1.2.16) for the addition of PEP to D-arabinose 5-phosphate33. DA HP synthase (EC 4.1.2.15) produces 3-deoxy-L>-arer/>/>io-heptulosonic acid 7-phosphate from PEP and D-erythrose 4-phosphate35. 

Deoxy-3-fluoro-D-glucose (see Section 11,2), a weak substrate for yeast hexokinase, is phosphorylated enzymically - to give the 6-phosphate 588, which is transformed into 2-deoxy-2-fluoro-D-arabinose 5-phos-phate (589) by lead tetraacetate oxidation. 

A monoaminopentose, 4-amino-4-deoxy-L-arabinose, is known as a component of some Gram-negative bacteria. It is linked, as the )5-pyranosyl phosphate (18), to a 2-amino-2-deoxy-y -D-glucopyranosyI residue in the lipid A part of the LPS. ... 

The biosynthesis of Kdo and neuraminic acid is known to involve enol-pyruvate phosphate and D-arabinose or 2-acetamido-2-deoxy-D-mannose, respectively. Nothing is known about the biosynthesis of all the other glycu-losonic acids. One interesting problem is, for example, whether the two 5,7-diamino-3,5,7,9-tetradeoxynonulosonic acids are synthesized analogously to neuraminic acid, from a three- and a six-carbon fragment, by modification of neuraminic acid on the sugar nucleotide level, or by a third, less obvious route. 

That the same enzyme,28 sucrose phosphorylase, is involved in the reaction of L-arabinose is indicated by the following observation. When L-arabinose is added to a mixture containing the enzyme, D-glucose-1-phosphate and D-fructose, of which the last is present in insufficient concentration to give the maximum rate of sucrose formation, an increase... 

Most of the structural and biochemical work related to KDO is based on the estimation of the compound or its derivatives by the periodate-thiobarbituric acid (TBA) assay in its various modifications. Indeed, KDO (see Fig. 3) was discovered9 through the formation of a characteristic, purple, TBA chromophore (Xmax 549 nm) from its 8-phosphate (2), which is the product of the condensation of D-arabinose 5-phosphate with enolpyruvate phosphate, catalyzed by 3-deoxy-8-0-phosphonooctulosonate synthetase (EC 4.1.2.16) (see Scheme 1 and Section V,2). 

These circumstances became apparent to the authors when they attempted to study the formation of KDO 8-phosphate as catalyzed by purified bacterial extracts. These extracts did not catalyze the formation of KDO 8-phosphate from D-ribose 5-phosphate, but required D-arabinose 5-phosphate as the substrate Heath and Ghalambor29 showed that the KDO 8-phosphate synthetase reaction, observed in Pseudomonas extracts by Levin and Racker, is also catalyzed by extracts from Escherichia coli strains 0 111 B4 and J-5. Rick and Osborn136 showed that the KDO 8-phosphate synthetase from a Salmonella typhimurium mutant conditionally defective in cell-wall synthesis had a KM of 6 mM as compared to a KM of 170 pM for the enzyme from wild-type cells. 

A comprehensive study of KDO 8-phosphate synthetase has been reported by Ray.137 The author purified the enzyme 450-fold from crude extracts of Escherichia coli B cells. The synthetase has a molecular mass of 90,000 6,000 daltons and is composed of three identical subunits having an apparent molecular mass of32,000 4,000 daltons. Two pH optima were observed, one being at pH 4.0-6.0 in succinate buffer, and the other, at pH 9.0 in glycine buffer. The isoelectric point of the enzyme is 5.1. The enzyme has an apparent KM for D-arabinose 5-phosphate of 20 pM and an apparent KM for enolpyruvate phosphate of 6 pM. 

Salmonella typhimurium mutant.136-149 The defect of this mutant lies in the apparent KM (D-arabinose 5-phosphate) of its KDO 8-phosphate synthetase (compare this Section, 2). This KM increases more than 25-fold between 29 and 42°, so that the cells become increasingly dependent on exogenously supplied D-arabinose 5-phosphate as the growth temperature is raised. Cessation of LPS biosynthesis under nonper-missive conditions is accompanied by the accumulation of a KDO-de-ficient, precursor molecule.149 Lehmann150 and Rick and coworkers151 described studies directed at the isolation and chemical characterization of such lipid A precursors (for example, 133, Scheme 39). The... 

Several observations regarding this aspect have been published, and are briefly mentioned here. 5,6-Dideoxy-6-C-phosphono-D-arabino-hexofuranose (135), an isosteric phosphonate analog of D-arabinose 5-phosphate, is apparently converted, in the presence of enolpyruvate phosphate, into 3,8,9-trideoxy-9-C-phosphono-D-mcmno-2-nonulosonic acid (136) under catalysis by KDO 8-phosphate synthetase from Escherichia coli K 235. Compound 136, an isosteric phosphonate analog of KDO 8-phosphate, is a product inhibitor of the synthetase, and, by the nature of the phosphonate group, is not subject to dephosphorylation as catalyzed by KDO 8-phosphate phosphatase156 (see Scheme 40). Compound 119 (see Scheme 33) is a weak inhibitor of KDO 8-phosphate synthetase.81 KDO inhibits KDO 8-phosphate phosphatase,139 and D-ribose 5-phosphate has an inhibitory... 

D-Ribono-1,4-lactone (1) readily condenses with acetone, under acidic catalysis with mineral acids or anhydrous copper sulfate, to give 2,3-0-isopropylidene-D-ribono-1,4-lactone (16a), which was employed for the synthesis of 5-deoxy and 5-0-substituted derivatives of D-ribono- 1,4-lactone and D-ribitol (24). Acid removal of the 1,3-dioxolane protecting group gave products having probable inhibitory activity of arabinose 5-phosphate isomerase (25). Other applications of 16a for the synthesis of natural products will be discussed later. 

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