RESUMO
Dietary titanium as TiO2+ improved animal growth during infancy while inhibiting the metabolism of intestinal bacteria. TiO2+ was also found capable of inhibiting human cytomegalovirus in tissue culture. These and other findings indicate TiO2+ improves infant growth by acting as an antibacterial and antiviral agent. The behavior of TiO2+ stands in contrast to that of TiO2, which is inert.
Assuntos
Crescimento/efeitos dos fármacos , Titânio/farmacologia , Animais , Animais Recém-Nascidos , Antivirais/farmacologia , Bactérias/efeitos dos fármacos , Células Cultivadas , Citomegalovirus/efeitos dos fármacos , Dieta , Suplementos Nutricionais , Fezes/microbiologia , Humanos , Masculino , Camundongos , Titânio/toxicidadeRESUMO
Ti4+ in soil is a natural antibiotic mobilized by bacteria-generated H+. When added to the diet of young mice, Ti4+ enhanced their growth. These and observations of others indicate that Ti4+ has a variety of biological roles.
Assuntos
Bactérias/crescimento & desenvolvimento , Sistema Digestório/microbiologia , Microbiologia do Solo , Titânio/farmacologia , Titânio/fisiologia , Animais , Animais Recém-Nascidos , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Disponibilidade Biológica , Peso Corporal , Dieta , Sistema Digestório/efeitos dos fármacos , Fezes , Concentração de Íons de Hidrogênio , Masculino , Camundongos , Oxalatos/farmacologiaRESUMO
An alternative approach to the development of clinically useful protease inhibitors was investigated. The approach utilized coordination chemistry of transition metal ions rather than substrate analogs to block active sites of these enzymes. In the case of serine proteases it was found that aqueous Ti(IV) is a potent inhibitor of the trypsin subclass, but not the chymotrypsin subclass. The direct binding of Ti(IV) to trypsin was made possible by the presence of a free carboxyl group at the bottom of the substrate binding pocket of the enzyme, and the five-coordinate geometry of TiO(SO4)(H2O). Although initial binding of Ti(IV) was reversible, it was followed in time by irreversible inhibition. Direct binding of octahedral or tetrahedral metal ion complexes was prevented by the inability of the enzyme active sites to promote formation of a five-coordinate transition state of the metal ion required for reaction. These studies demonstrate the ability of direct metal ion binding as a way to enhance blocking of enzyme active sites as compared with that of traditional organic inhibitors. Application of these findings was investigated by measuring the affect Ti(IV) had on growth of Escherichia coli, Salmonella typhimurium, and Pseudomonas aeruginosa. Five-coordinate titanyl sulfate completely inhibited the growth of these organisms. This suggests that five-coordinate titanyl sulfate, which is easier and less expensive to manufacture than conventional antibiotics, may be useful in controlling endemic infections of E. coli and S. typhimurium.
