No abstract

Although the need for selenium in human and animal nutrition is well recognized, the question concerning the proper form of selenium for supplemental use is still being debated. Ideally, selenium should be supplemented in the form in which it occurs naturally in foods. Because the L-isomer of selenomethionine (Se-met) is a major natural food-form of selenium, synthetic L-Se-met or enriched food sources thereof such as selenium yeast are appropriate supplemental forms of Se for humans; for animals, DL-Se-met is acceptable. Ingested Se-met is either metabolized directly to reactive forms of selenium or stored in place of methionine in body proteins. Se-met metabolism is closely linked to protein turnover. At constant intakes in the nutritional range, tissue Se levels increase until a steady state is established, preventing the build-up to toxic levels.

Lithium is found in variable amounts in foods; primary food sources are grains and vegetables; in some areas, the drinking water also provides significant amounts of the element. Human dietary lithium intakes depend on location and the type of foods consumed and vary over a wide range. Traces of lithium were detected in human organs and fetal tissues already in the late 19th century, leading to early suggestions as to possible specific functions in the organism. However, it took another century until evidence for the essentiality of lithium became available. In studies conducted from the 1970s to the 1990s, rats and goats maintained on low-lithium rations were shown to exhibit higher mortalities as well as reproductive and behavioral abnormalities. In humans defined lithium deficiency diseases have not been characterized, but low lithium intakes from water supplies were associated with increased rates of suicides, homicides and the arrest rates for drug use and other crimes. Lithium appears to play an especially important role during the early fetal development as evidenced by the high lithium contents of the embryo during the early gestational period. The biochemical mechanisms of action of lithium appear to be multifactorial and are intercorrelated with the functions of several enzymes, hormones and vitamins, as well as with growth and transforming factors. The available experimental evidence now appears to be sufficient to accept lithium as essential; a provisional RDA for a 70 kg adult of 1,000 microg/day is suggested.

No abstract

Results of kinetic measurements are presented which indicate that the reactions of alkyl halides with vitamin B^,, cobaloximes(I), and other Co(I) chelates proceed by a classical Sn2 mechanism, the Co(I) centers being some of the most powerful nucleophiles known. The evidence for this mechanism providing the dominant reaction pathway is based mainly on the analysis of substrate structural effects on the substitution rates. Although the absolute reactivities of the Co(I) nucleophiles are up to 107 times greater than those, e.g., of iodide ion, the relative reactivities with various substrates are very similar. Surprisingly, the rates of reactions of the alkyl halides studied are no more sensitive to steric effects of the corrin ligand system than to those of the cobaloxime moiety. Steric hindrance by out-of-plane corrin ligands appear in later stages of the Co-C bond formation process, as evidenced by the instability of secondary alkyl cobalamins in contrast to the corresponding cobaloxime derivatives. The factors influencing the nucleophilicity of the Co(I) chelates, in particular, the effects of axial bases, ligand structure, and possible mechanistic alternatives of the alkylation reactions are discussed. The presence of the coordinated 5,6-dimethylbenzimidazole does not cause a substantial change of the Co(I) nucleophilicity of vitamin Bn"(5) G.

Selenium (Se) exerts its anticarcinogenic effects by multiple mechanisms. In the physiological dosage range, Se appears to function as an antimutagenic agent, preventing the malignant transformation of normal cells and the activation of oncogenes. These protective effects of Se seem to be primarily associated with its presence in the glutathione peroxidases, which are known to protect DNA and other cellular components from damage by oxygen radicals. Selenoenzymes are also known to play roles in carcinogen metabolism, in the control of cell division, oxygen metabolism, detoxification processes, apoptosis induction and the functioning of the immune system. Other modes of action, either direct or indirect, may also be operative, such as the partial retransformation of tumor cells and the inactivation of oncogenes. However, the effects of Se in the physiological dosage range are not attributable to cytotoxicity, allowing Se to be defined as a genuine nutritional cancer-protecting agent. The anticarcinogenic effects of Se are counteracted by Se-antagonistic compounds and elements. For maximal utilization of its cancer-protective potential, Se supplementation should start early in life and be maintained over the entire lifespan. In addition, exposure to Se antagonists and carcinogenic risk factors should be minimized by appropriate dietary and lifestyle changes.

The highly unusual organometallic chemistry of cobalt in vitamin Bi2 and its derivatives can now be studied with surprisingly simple model compounds.

Using data for 27 Texas counties from 1978-1987, it is shown that the incidence rates of suicide, homicide, and rape are significantly higher in counties whose drinking water supplies contain little or no lithium than in counties with water lithium levels ranging from 70-170 micrograms/L; the differences remain statistically significant (p less than 0.01) after corrections for population density. The corresponding associations with the incidence rates of robbery, burglary, and theft were statistically significant with p less than 0.05. These results suggest that lithium has moderating effects on suicidal and violent criminal behavior at levels that may be encountered in municipal water supplies. Comparisons of drinking water lithium levels, in the respective Texas counties, with the incidences of arrests for possession of opium, cocaine, and their derivatives (morphine, heroin, and codeine) from 1981-1986 also produced statistically significant inverse associations, whereas no significant or consistent associations were observed with the reported arrest rates for possession of marijuana, driving under the influence of alcohol, and drunkenness. These results suggest that lithium at low dosage levels has a generally beneficial effect on human behavior, which may be associated with the functions of lithium as a nutritionally-essential trace element. Subject to confirmation by controlled experiments with high-risk populations, increasing the human lithium intakes by supplementation, or the lithiation of drinking water is suggested as a possible means of crime, suicide, and drug-dependency reduction at the individual and community level.