Radical dephosphorylation

Alkaline phosphatase catalyzes the dephosphorylation of a mmber of artificial substrates ( ) including 3-glycerophosphate, phenylphosphate, p-nitrophenylphosphate, thymolphthalein phosphate, and phenolphthalein phosphate. In addition, as shown recently for bacterial and human enzymes, alkaline phosphatase simultaneously catalyzes the transphosphorylation of a suitable substance which accepts the phosphoryl radical, thereby preventing the accumulation of phosphate in the reaction mediim (25). 

Acid phosphatase catalyzes the dephosphorylation of an artificial organic substrate, such as B-glycerophosphate, phenyl-phosphate or thymolphthalein monophosphate. The analyst may measure either the phosphate or the organic radical liberated. 

Weiss (W2) attributes the destruction of microorganisms to the OH and H radicals formed in the water near the nuclear material (Sec. IIIB2b). These radicals inactivate cells by initiating deamination and dephosphorylation of the nucleic acids, thus weakening the nucleo-protein structure. This and other proposed chemical mechanisms have recently been discussed by Gray (G12). 

The radical-induced dephosphorylation of sugar phosphates (see Sect. HI,3) and the scission of DNA strands (see Sect. Ill,6) are mainly due to these reactions, at least in the absence of molecular oxygen. 

Scheme 11.—Dephosphorylation Reactions Starting from the Radical at C-4 of D-Ri-bose 5-Phosphate.

With D-ribose 5-phosphate, dephosphorylation largely occurs from the radical /3 to the phosphate group (59, in Scheme 11) some principal aspects of the mechanism have already been discussed in Section II,lc. The resulting product is 5-deoxy-D-eryfhro-pentos-4-ulose (61) (seeTable V, and reactions222 and222). The yield of61 is increased in... 

Dephosphorylation can also occur from the radical a to the phosphate group (62, in Scheme 12). Oxidation of this radical (62) leads to a carbonium ion (reaction 125) which, in its subsequent reactions (126 and 127), eliminates the phosphate group, affording ribo-pentodial-dose (63). Oxidation by other radicals in this system is not very effective, and is more readily brought about by Fe3+ ions [compare G(63) in NaO and N20/Fe3+ see Table V]. 

Scheme 12.—Dephosphorylation Reactions Starting from the Radicals at C-5 and C-3 of D-Ribose 5-Phosphate.

Stelter L, von Sonntag C, Schulte-Frohlinde D (1975a) Radiation chemistry of DNA-model compounds VIII. Dephosphorylation products from reactions of OH radicals with ribose-5-phos-phate in aqueous solution. The effect of oxygen. Z Naturforsch 30b 609-615 Stelter L, von Sonntag C, Schulte-Frohlinde D (1975b) Radiation chemistry of DNA-model compounds, VII. On the formation of 5-deoxy-D-eryffrro-pentos-4-ulose and the identification of 12 further products from y-irradiated aqueous solutions of ribose-5-phosphate. Z Naturforsch 30b 656-657... 

It is possible to measure the formation of various radicals such as reactive oxygen species in cells. Reactive oxygen species (ROS) activate the nuclear factor of activated T cell transcription factor (NFAT), which is associated with its dephosphorylation, nuclear translocation, and increased affinity for DNA binding. Vanadium activation of nuclear factor of activated T cells (NFAT) was found to correlate with formation of the ROS H202 and was dependent upon the activity of calcium channels [39], In activated human neutrophiles, vanadium(II), (III), and (IV) increased hydroxyl radical formation and attenuation of myeloperoxidase activity, whereas V(V) did not show these effects. Similar results were seen in a cell-free system [40], Increased lipid peroxidation in liver but not in kidneys was found in normal rats treated with vanadate [41]. 

Radical-based dephosphorylation via a phosphonyl radical constitutes one formulation for the mechanism of C-P bond cleavage during microbial degradation of organophospho-nates.80 Frost has demonstrated that anhydrides 117 derived from phosphonic acid and thiohydroxamic acid react in a chain sequence with thiols, Bu3SnH and CC14 to give dephosphoryl-... 

The major psychedelic agent in psilocybian mushrooms is psilocybin— the first indole derivative discovered to contain phosphorus. When ingested, the phosphorus radical is immediately "dephosphorylated by an intestinal enzyme, alkaline phosphatase, into psilocin and phosphoric acid Animal experiments suggest that psilocybin and psilocin appear at similar chemical concentrations at about the same time in various organs. Thus, the phosphorus radical is generally considered "dead weight in terms of psychoactivity. 

Inhibition of PKC by a-tocopherol in vascular smooth muscle cells is observed to occur at concentrations of a-tocopherol close to those measured in healthy adults [24]. P-Tocopherol per se is not very effective but prevents the inhibitory effect of a-tocopherol. The mechanism involved is not related to the radical scavenging properties of these two molecules, which are essentially equal [25]. In vitro studies with recombinant PKC have shown that inhibition by a-tocopherol is not caused by tocopherol-protein interaction, a-Tocopherol does not inhibit PKC expression as well. Inhibition of PKC activity by a-tocopherol occurs at a cellular level by producing dephosphorylation of the enzyme, whereby P-tocopherol is much less potent [26]. Dephosphorylation of PKC occurs via protein phosphatase PP2A, which is activated by the treatment with a-tocopherol [26-28]. 

The mechanism of cytoprotection for amifostine is similar to that of other thiols. Once dephosphoryl-ated to actifostine [equation 270], the active thiol can scavenge oxygen free radicals (Ohnishi et al. 1992) and bind to a variety of electrophilic agents. 

The free radical induced reactions at the deoxyribose moiety of DNA could result into DNA strand breaks. These reactions involve dephosphorylation of the sugar phosphate esters. 

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