Arsonates as Analogues of Natural Phosphates or Phosphonates

If the action of the enzyme is to transfer the phospho group, e.g., to water in a hydrolysis, or intramolecularly, e.g., in converting 3-phosphoglycerate into 2-phosphoglycerate (48), it cannot transform the phosphonomethyl analogue. This is because R—CH2 is an incompara- 

Webster et al. (41) showed that enzymes could be used to convert synthetic H203P—CH2—CH2—CHOH—COOH, the analogue of 3-phosphoglycerate, into the corresponding phosphonomethyl analogue of fructose 6-phosphate (Fig. 2), which they isolated. They obtained evidence for the enzymic conversion of this into the analogue of glucose 

6-phosphate [these two analogues were later separated (52)], and on into the analogues of 6-phosphogluconate (see 53) and ribulose 5-phosphate. It is therefore possible that enzymes would produce such analogues of nucleotides, which could be used to insert unhydrolyzable bonds into nucleic acids, at least bonds not hydrolyzed by those nucleases that form 3 -phosphates. 

A somewhat different kind of futile cycle was obtained by Visedo-Gonzalez and Dixon (60). This arose from the fact that the incorporation of ethanolamine (i.e., 2-aminoethanol) into phospholipids starts with the reaction of its phosphate with CTP (Fig. 5). This forms the compound 

This use by an enzyme of R—P03H2 in place of R— —P03H2 is fairly unusual it is normally only R—CH2—P03H2 (see Section IV,A) that will be transformed. It was therefore not surprising that R— As03H2 proved to be a substrate (60). At least, we presume that it was, but the expected product (Fig. 5, Reaction 2) would be a phosphorylated 

A remarkable reaction of the phospho group is its transfer onto carbon in the biosynthesis of the C—P bond (Fig. 6). Incidentally, this leads to a difficulty with nomenclature, because the group -PO3H2, which is known to chemists as phosphono, is called phospho only when on a heteroatom (64), so the transfer changes its name Despite much ealier guessing from labeling patterns that phosphoenolpyruvate was the source of the C—P bond, it was only in 1988 (65, 66) that the enzyme responsible was isolated. The difficulty proved to be that the equilibrium favors phosphoenolpyruvate by about 2000-fold (67), so that assays only detected the enzyme in the direction contrary to biosynthesis evidently the biosynthesis takes place because subsequent reac- 

The enzyme that hydrolyzes phosphonoacetaldehyde (Fig. 7) is bacterial and provides a pathway for breaking the C—P bond. It has a mechanism like that of aldolase (69- 71) in that an imine forms between the carbonyl group of substrate and an amino group of the enzyme since this imine is hydronated at neutral pH, the electron attraction is increased, and this facilitates the breakage of the C—P bond. When arsonoacetaldehyde was tried in this reaction (63), it proved not to be a substrate, and it did not inhibit the enzyme appreciably. 

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B. The Place of Arsenite in the Detoxification of Arsenate Arsonates as Analogues of Natural Phosphates or Phosphonates... 

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