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K P McConnell

Publications and source records attributed to K P McConnell.

At least 19 recordsLinked to original sources
PubMed1988

S-adenosyl-L-methionine:thioether S-methyltransferase, a new enzyme in sulfur and selenium metabolism.

The final urinary excretion product of selenium detoxification is trimethylselenonium ion. An assay has been developed for the enzyme, S-adenosylmethionine:thioether S-methyltransferase, responsible for this final methylation reaction. This assay employed high pressure liquid chromatography separation and quantitation of the trimethylselenonium ion produced by thioether methyltransferase acting on S-adenosylmethionine and dimethyl selenide. The enzyme was shown to reside primarily in the cytosol of mouse lung (30 pmol/mg protein/min) and liver (7 pmol/mg protein/min). Purification from mouse lung to a preparation that exhibited a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis was achieved by DEAE, gel filtration, and chromatofocusing chromatographies. Thioether methyltransferase is monomeric with a molecular weight of 28,000 and has a pI of 5.3. The pH optimum was 6.3, and Km values for dimethyl selenide and S-adenosylmethionine were 0.4 and 1.0 microM, respectively. The enzyme was inhibited 50% by 25 microM sinefungin, an analog of S-adenosylmethionine, or 40 microM S-adenosylhomocysteine, the reaction product. Pure thioether methyltransferase methylated selenium in dimethyl selenide, tellurium in dimethyl telluride, and S in dimethyl sulfide and many other thioethers. These data suggest a general role for this novel enzyme in the synthesis of onium compounds with increased aqueous solubility helpful in their excretion.

Animals↗
PubMed1987

Periodate-oxidized adenosine inhibits the formation of dimethylselenide and trimethylselenonium ion in mice treated with selenite.

The metabolic detoxification of selenite and many other selenium compounds involves a series of S-adenosylmethionine-dependent methylations yielding dimethylselenide (DMSe), which is exhaled, and trimethylselenonium ion (TMSe), which is excreted in the urine. This paper shows that periodate-oxidized adenosine (Adox) inhibits these methylation reactions in vivo and increases the toxicity of selenite. When Adox was injected in mice at 100 mumol/kg 30 min before injection of [75Se]selenite at 0.4 mg Se/kg the appearances of [75Se]DMSe in the breath and [75Se]TMSe in the liver were completely inhibited for 90 min. This was mediated by accumulation of S-adenosylhomocysteine, the methyltransferase inhibitor, in the livers of Adox-treated mice due to inhibition of its hydrolase enzyme. During 24 h, Adox-treated mice excreted no detectable urinary [75Se]TMSe and exhaled only 20% as much [75Se]DMSe as controls. The urine of Adox-treated mice also contained S-adenosylhomocysteine at a level (ca. 4 mM), 200 times that of untreated mice, which provided a convenient index of methylation potential in the intact animal. When three groups of three mice each were injected with 100 mumol Adox/kg, selenite at 4 mg Se/kg, or a combination of the two, the mice receiving the combination were dead within 2 days, while the mice in the other two groups all survived at least 4 days. These results verify the enzymatic nature of selenium methylation in vivo, support its importance in detoxification, and indicate the value of Adox in further studies of selenium metabolism.

Adenosine↗
PubMed1985

Influence of selenium on the growth of N-nitrosomethylurea-induced mammary tumor cells in culture.

Selenium is an essential dietary trace element which has anticancer properties. Among its effects in rats, selenium has been shown to inhibit the development of carcinogen-induced mammary tumors by interfering with the postinitiation, promotion phase of carcinogenesis. We studied the effects of selenium on the growth of rat mammary tumor cells in primary culture. Our objective was to determine whether selenium had any direct influence on cell growth which might explain its influence on tumor development. Rat mammary tumors were induced by N-nitrosomethylurea. Tumor epithelium was prepared by collagenase dispersion and the cells were separated by Ficoll gradient centrifugation. The tumor epithelium was grown in primary culture using a defined serum-free medium. The addition of low concentrations of sodium selenite, less than 1.0 micrograms/ml, stimulated tumor cell proliferation. Protein synthesis and the production of type IV collagen increased within the first hour of exposure, prior to any measurable increase in DNA synthesis. Concentrations of selenite greater than 1.0 micrograms/ml inhibited cell proliferation, the synthesis of protein, and the replication of DNA in a dose-related manner. These studies demonstrated that selenium has the potential to influence the postinitiation phase of rat mammary tumorigenesis by directly altering the growth of tumor cells, possibly through the regulation of protein synthesis.

Adenocarcinoma↗
PubMed1980

The relationship of dietary selenium and breast cancer.

An inverse relationship exists between dietary selenium (Se) concentrations and the incidence of human breast cancer. The addition of Se to the diet has been shown to decrease the incidence of spontaneous murine mammary tumors. We compared the serum Se concentrations in breast cancer patients with those of women without breast cancer. Serum was collected from 35 women with breast cancer. Nineteen of these women had infiltrating ductal carcinoma and two had Paget disease of the nipple. Nine women had lymph nodal metastases at the time of mastectomy, four had definite evidence of metastatic disease when the blood samples were drawn, and the disease process of one patient was unclassified. Samples from 27 women known to be free of breast cancer were used as controls. The difference noted between the mean serum Se concentrations of breast cancer patients and controls were found to be significant.

Adult↗
PubMed1978

Serum selenium and reticuloendothelial tumors.

Serum selenium levels were determined by neutron activation analysis on 59 patients with a variety of reticuloendothelial neoplasms. Correlations were attempted between the widely variable range in the serum concentrations of the trace element with the parameters employed in this study. Therapy, particularly less than six weeks initiation, produced elevations in the serum selenium levels.

Female↗
PubMed1977

Reaction of selenium with immunoglobulin molecules.

Radioactive selenite reacts with purified human and goat immunoglobulins at acidic and neutral pH. The antigenic properties of the immunoglobulins are retained during the selenium labelling as shown by immunoelectrophoresis and autoradiography. Pepsin digests of 75Se-labelled IgG possess 75Se both in the (Fab')2 fraction and in the low molecular weight peptides derived from the Fc domains. Alpha-1-acid glycoprotein, ribonuclease, and lysozyme are also labelled by this procedure. Enhancement of 75Se incorporation by urea, guanidinium chloride, mercaptoethanol, sodium sulfite and carrier selenite is interpreted as an effect of destabilization of IgG disulfide bonds. Up to 1.4 g atoms Se per mol IgG have been incorporated. We assume that selenite is cleaving disulfides by a process akin to sulfitolysis. The lability of the isolated 75Se-labelled IgG to high concentrations of mercaptans and sulfite is consistent with this idea. These 75Se-labelled proteins may be useful in structure studies and radioimmunoassay.

Animals↗
PubMed1976

Relationship between serum selenium levels and patients with carcinoma.

Serum selenium levels were determined by neutron activation analysis on 110 patients with carcinoma. An attempt was made to correlate the wide range in the serum concentrations of the trace element with the parameters employed in this study. An association was noted between the serum selenium levels and patient survival time, incidence of multiple primary malignancies, rate of recurrence of the primary lesion and the extent of local and disseminated involvement.

Female↗
PubMed1975

Selenium levels in human blood and tissues in health and in disease.

The levels of selenium in human sera and pancreatic, hepatic and synovial tissues were measured. An attempt was made to correlate the selenium level with certain disease states. Selenium was determined by nerutron activation analysis, using the 17.4 second half-life isotope 77mSe with a sensitivity of 2ppb. Serum-bound selenium was determined in normal individuals and individuals with various malignancies, and medical and surgical disorders. Tissue selenium was assayed in diseased and normal pancreases, livers, and synovial membranes. A wide variation was observed both in the serum selenium content of patients with a malignancy and in postmoren pancreatic and synovial showing histopathological changes. Significantly lower selenium values were observed in sera from cancer patients than from normal individuals. Higher values were generally observed in patients with primary neoplasms of the reticuloendothelial system. Higher tissue concentrations were obtained in synovia from patients with rheumatoid arthritis and in pancreatic tissues associated with histopathological changes.

Arthritis, Rheumatoid↗