An integration of knowledge concerning regulation of metallothionein expression with research on metallothionein's proposed functions is necessary to delineate how this metalloprotein affects cellular processes, especially zinc metabolism. Metallothionein expression is driven by a number of physiological mediators through several response elements in the metallothionein gene promoter. Cellular accumulation of metallothionein depends on both gene expression and protein degradation. Both depend largely on availability of cellular zinc derived from the dietary zinc supply. Metallothionein expression is related to zinc accumulation in certain organs. Evidence has been produced, which suggests that metallothionein could act in a number of biochemical processes. It may act in zinc trafficking and/or zinc donation to apoproteins, including zinc finger proteins that act in cellular signaling and transcriptional regulation. As a result, metallothionein expression may affect a number of cellular processes including gene expression, apoptosis, proliferation and differentiation. The ability of metallothionein to exchange other metals with zinc in these proteins may explain a role in metal toxicity. Similarly, mobilization of zinc from metallothionein by oxidative stresses may explain its proposed antioxidant function. Apparent good health of metallothionein-deficient mice argues against a critical biological role for metallothionein; however, expression may be critical in times of stress.

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, respectively). However, the rate of overall homocysteine remethylation (ϳ8 mol⅐kg Ϫ1 ⅐h Ϫ1) was twice that of previous reports, which suggests a larger role for homocysteine remethylation in methionine metabolism than previously thought. By use of estimates of intracellular [3-13 C]serine enrichment based on a conservative correction of plasma [3-13 C]serine enrichment, serine was calculated to contribute ϳ100% of the methyl groups used for total body homocysteine remethylation under the conditions of this protocol. This contribution represented only a small fraction (ϳ2.8%) of total serine flux. Our dual-tracer procedure is well suited to measure the effects of nutrient deficiencies, genetic polymorphisms, and other metabolic perturbations on homocysteine synthesis and total and folate-dependent homocysteine remethylation. methionine; methylation cycle; cystathionine ELEVATED PLASMA HOMOCYSTEINE CONCENTRATION is considered an independent risk factor for the development of cardiovascular disease (5,30,32). Accordingly, many investigators have sought to define the genetic and environmental factors that affect plasma homocysteine concentration. Associations exist between plasma homocysteine concentrations and gene polymorphisms, as well as lifestyle and other environmental factors (5). Strong evidence implicates nutritional deficiencies of folate, vitamins B 6 and B 12 , and the methylenetetrahydrofolate reductase (MTHFR) 677C 3 T polymorphism as causes of elevated plasma homocysteine concentration (12, 25). Folate and vitamin B 6 deficiencies and the MTHFR 677C 3 T polymorphism are thought to increase circulating homocysteine concentrations by decreasing the availability of 5-methyltetrahydrofolate (5-CH 3 THF) and thereby inhibiting homocysteine remethylation (24). However, a causal relationship between reduced homocysteine remethylation and hyperhomocysteinemia under these conditions has not been confirmed in humans in vivo.Steady-state plasma homocysteine concentration is not solely a function of the rate of its removal by remethylation but is also affected by the rates of homocysteine production, catabolism through transsulfuration, and loss in renal excretion (24). Specific measurements of homocysteine metabolism through these individual pathways are needed to clarify why homocysteine concentration is elevated by particular genetic variations as well as by nutritional and other environmental conditions. To test the hypothesis that homocysteine remethylation is compromised when 5-CH 3 THF availability is reduced, homocysteine remethylation rates must be measured in individuals affected by these homocysteineelevating factors.Remethylation rates have been measured in humans in vivo by use of methionine tracers labeled with stable isotopes at both the carboxyl and methyl groups or else by measurements of separate methyl-and carboxyl-labeled methionine tracers in primed constant infusion experiments (18,26). By use of these methodologies, the effects of dietary sulfur amino acid intake, sex, age, prandial statu...

Stimulation of gastrointestinal tract maturation is 1 of the many benefits of human milk. Human milk oligosaccharides (HMOs) are abundant in human milk and are reported to promote enterocyte differentiation in vitro. The objective of this study was to assess the impact of 3 predominant HMOs on multiple aspects of enterocyte maturation in vitro. Ranging from crypt-like to differentiated enterocytes, we used the well-characterized intestinal cell lines HT-29 and Caco-2Bbe to model early and late stages of differentiation, respectively. With this model of the crypt-villus axis made up of preconfluent HT-29, preconfluent Caco-2Bbe, and postconfluent Caco-2Bbe cultures, we characterized the impact of lacto-N-neotetraose (LNnT), 2'-fucosyllactose (2'FL), and 6'-sialyllactose on epithelial cell kinetics and function. All 3 HMOs dose-dependently inhibited cell proliferation in undifferentiated HT-29 and Caco-2Bbe cultures (P < 0.05). In contrast to previous reports, only treatment with 2'FL at concentrations similar to human milk increased alkaline phosphatase activity by 31% (P = 0.044) in HT-29 cultures and increased sucrase activity by 54% (P = 0.005) in well-differentiated Caco-2Bbe cultures. LNnT at concentrations similar to that reported for human milk increased transepithelial resistance by 21% (P = 0.002) in well-differentiated Caco-2Bbe cells. In summary, all 3 HMOs reduced cell proliferation in an epithelial cell model of the crypt-villus axis. However, effects on differentiation, digestive function, and epithelial barrier function differed between the HMOs tested. These results suggest differential roles for specific HMOs in maturation of the gastrointestinal tract.

Moderate vitamin B-6 deficiency does not significantly alter the rates of homocysteine remethylation or synthesis in healthy young adults in the absence of dietary methionine intake.

Collectively, the data indicate that GOS may enhance mucosal barrier function through direct stimulation of intestinal goblet cells.

Nanocrystals of pure, Cu2+ and Fe3+ doped SnO2 have been prepared by a sol−gel route and were investigated by a combination of EXAFS and XRPD measurements. Surface doped samples were also studied, and these were prepared by immersing pure nanocrystals in aqueous solutions of the dopant cations. The XRPD results showed the average size of the crystallites when freshly prepared was 2−3 nm and was not affected by the dopant. The Sn K-edge EXAFS of the pure SnO2 nanocrystals was consistent with their size and suggested the level of disorder in the crystallites was comparable to that in bulk SnO2. The K-edge EXAFS of the dopants showed that up to at least 10 mol % nominal doping of both Cu2+ and Fe3+ ions in sol−gel prepared samples were situated on Sn4+ sites in the SnO2 cassiterite lattice. In the case of the surface doped samples the EXAFS showed no penetration of the dopant into the SnO2 lattice. The growth of the crystallites on heating was monitored by XRPD and was found to become clearly evident at about 400 °C. The effect of the dopants was to lower the growth rate of the nanocrystals. Heating the doped sol−gel prepared samples yielded EXAFS spectra that indicated the dopants gradually moved to surface regions of the crystallites. In the case of the nominally 10 mol % Fe3+ doped sample, heating for 1 h at 900 °C caused the precipitation of iron oxide. Heating the surface doped samples up to 900 °C did not cause a penetration of the dopant into the SnO2 lattice.

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