Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.2 (guanylate cyclase)
 8,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Perfluoroalkyl halides (PFHs) are synthetic products widely used in various fields. Perfluorooctyl bromide (PFB) is used in medicine as a component of blood substitutes and for artificial lung ventilation. In both cases, it is considered a completely inert compound acting as a solvent for oxygen. However, there are many reports of PFH-induced intoxication, including lethal cases. Mechanisms underlying toxic effects of this compound remain unknown. In this study, we demonstrate that the reduced form of cobalamin (vitamin B12) typical for B12-dependent enzymes can catalyze the reactions of perfluoroalkylation, aromatic substitution, or addition by double bonds. Synthesis of perfluoro derivatives from PFHs during catalysis by cob(I)alamin-like super nucleophiles is a new possible mechanism responsible for in vivo formation of highly toxic compounds from "chemically inert" substances widely used in medicine. Catalytic perfluoroalkylation might possibly contribute to nitric oxide depletion and modulation of activity of guanylate cyclase, cytochromes, NO-synthases, and other heme-containing proteins.
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PMID:Mechanism of perfluoroalkyl halide toxicity: catalysis of perfluoroalkylation by reduced forms of cobalamin (vitamin B12). 1475 34

Herein, the synthesis of novel hydrophobic and hydrophilic cobinamides via aminolysis of vitamin B12 derivatives that activate soluble guanyl cyclase (sGC) is presented. Unlike other sGC regulators, they target the catalytic domain of sGC and show higher activity than (CN)2Cbi.
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PMID:Synthesis of New Hydrophilic and Hydrophobic Cobinamides as NO-Independent sGC Activators. 2490 Apr 97