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Acetaminophen and its glucuronide, sulfate, N-acetyl-L-cysteinyl, and L-cysteinyl metabolites can be rapidly detected by 1H NMR spectroscopy of intact, untreated human urine. Study of the time course of excretion of these metabolites in five clinically normal men after ingestion of the usual 1-g therapeutic dose of the drug showed that the mean 24-h(More)
Human PHOSPHO1 is a phosphatase enzyme for which expression is upregulated in mineralizing cells. This enzyme has been implicated in the generation of P(i) for matrix mineralization, a process central to skeletal development. PHOSPHO1 is a member of the haloacid dehalogenase (HAD) superfamily of Mg2+-dependent hydrolases. However, substrates for PHOSPHO1(More)
Although details of the molecular mechanisms for the uptake of the essential nutrient zinc into the bloodstream and its subsequent delivery to zinc-requiring organs and cells are poorly understood, it is clear that in vertebrates the majority of plasma zinc (9-14 microM; approx. 75-85%) is bound to serum albumin, constituting part of the so-called(More)
Three cysteine-rich proteins of molecular weight 4000 to 7000, containing 4 to 7 gram atoms of cadmium, zinc, and copper per mole were isolated from Pseudomonas putida growing in 3 mM cadmium. The three proteins were induced during different phases of growth, and the smallest (molecular weight 3600; 3 gram atoms of cadmium) was released into the medium when(More)
Ruthenium complexes offer the potential of reduced toxicity, a novel mechanism of action, non-cross resistance and a different spectrum of activity compared to platinum containing compounds. Thirteen novel ruthenium(II) organometallic arene complexes have been evaluated for activity (in vitro and in vivo) in models of human ovarian cancer, and(More)
Bioorganometallic chemistry is a rapidly developing area of research. In recent years organometallic compounds have provided a rich platform for the design of effective catalysts, e.g. for olefin metathesis and transfer hydrogenation. Electronic and steric effects are used to control both the thermodynamics and kinetics of ligand substitution and redox(More)
500 MHz 1H NMR studies of rat urine are used to assess metabolic changes resulting from aging (0.5-20 months) and changes in diet (casein versus chow). Aging rats fed chow diets decrease their excretion of citrate and 2-oxoglutarate, while the output of taurine and creatinine increases. Only young rats (1 month or less postweaning) excrete significant(More)
Organometallic compounds offer broad scope for the design of therapeutic agents, but this avenue has yet to be widely explored. A key concept in the design of anticancer complexes is optimization of chemical reactivity to allow facile attack on the target site (e.g., DNA) yet avoid attack on other sites associated with unwanted side effects. Here, we(More)
The mechanism by which nucleotide-binding domains (NBDs) of ABC transporters power the transport of substrates across cell membranes is currently unclear. Here we report the crystal structure of an NBD, FbpC, from the Neisseria gonorrhoeae ferric iron uptake transporter with an unusual and substantial domain swap in the C-terminal regulatory domain. This(More)