Iron is a metal element indispensable for life. It usually plays important roles as reaction centers of the iron-containing proteins and enzymes, and is responsible for many physiological actions, e.g., conversion of bio-materials (biosynthesis and metabolism), bio-information (signal trasnduction) and bio-energy, through the ligand binding, acid-base and reductionoxidation reactions. Our group has had much interest in iron-containing proteins and enzymes, especially heme-containing proteins and enzymes (hemoproteins and heme-enzymes). Heme is a iron-porphyrin complexes. We are studying their molecular properties on the basis of their molecular structures, which can be crystallographycally determined using the SPring-8 Beam Lines. In this article, we focus on structure-function relationship of heme-containing oxygenases, oxygensensor proteins and nitric oxide reductases.

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Magnesium (Mg) has been recognized as an essential element since 1926. The standard daily intake of Mg is 340mg for males and 270 mg for females in Japan. Recently, food customs have changed and consumption of barley and miscellaneous cereals has been reduced. This has resulted in low Mg intake; one of the causes of type 2 diabetes.
In north-east Thailand, there has been an endemic health problem of sudden unexplained death syndrome (SUDS); called Lai Tai in the local language. In 1990s our project proceeded to clarify the cause. We assumed it might be due to food customs, and we hypothesized potassium (K) deficiency as a specific cause. But we noticed low levels of Mg in materials analyzed such as salt and the meals of local residents. First we tried analyses of two kinds of rice, regular rice and glutinous rice. Local residents in north-east Thailand consume much glutinous rice. Mg and K concentrations were analyzed according to the cooking process: soaking in water for one night and then steaming. In the case of glutinous rice, Mg concentrations were 41.6% after soaking, and 24.7% after soaking and steaming, compared with the uncooked value. K concentrations were 20.5% after soaking, and 11.7% after soaking and steaming, compared with the uncooked value. These values were lower than the values of regular rice prepared with the same process. Mg and K were similar levels in raw materials. It was clear that much Mg and K were lost during cooking. Then we tried an animal experiment. Mice at 8 weeks old were fed Mg-deficient or Mg/K-deficient diet. Mortality rate was higher in the Mg-deficient group than in the Mg/K-deficient group, and there were no sexual differences. In the Mg/K-deficient group the mortality rate was higher in males than in females. After one week of feeding with the Mg/K-deficient diet, some element concentrations were determined. Plasma Mg concentrations were 1/3 of those of the control, and in spite of this fact, heart muscle and kidney kept normal values in both sexes. The other elements determined were all statistically low in males, except for cobalt, which was higher, but in females molybdenum was lower and iron and cobalt were higher. After feeding a Mg-deficient diet for 2 weeks, testosterone was strongly reduced, but estrogen showed no change. These results suggested that homeostasis ability is lower in males than females, and that the cause of SUDS might correlate with Mg- and/or K- deficiency.

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Zinc has the most diverse functions in variety of biological processes. It plays crucial roles in catalytic, structural and regulatory functions. In a catalytic function, its involvement is ubiquitous in that each of six major enzyme classes has a representative that requires zinc. Recent proteome analysis reveals that about 1000 enzymes have a motif that potentially could bind zinc. Thus, the mechanisms for the activation or regulation by zinc of these enzymes should be elucidated in more detail. In the secretory pathway, a number of enzymes are properly folded and become functional by binding to zinc. Therefore, zinc transporters localized there and involved in zinc mobilization into the lumen play important roles. Two zinc transport complexes (ZnT5/ZnT6 heterodimers and ZnT7 homo-oligomers) are known to perform the task in vertebrate cells. This paper reviews current knowledge of the activation mechanism of secretory or membrane-bound zinc enzymes, emphasizing a novel mechanism for the activation of TNAP by ZnT complexes in the early secretory pathway.

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The in vivo effects of a water product supplemented with platinum (Pt) nanocolloid (PtW) showing in vitro antioxidant activity were studied by monitoring blood and urine components from healthy human subjects who ingested PtW. For comparison, the effects of another water product containing dissolved hydrogen gas (H₂) molecules were also examined in a similar manner. Under the conditions employed, serum lipid peroxide concentrations and urinary 8-hydroxydeoxyguanosine levels relative to creatinine did not significantly change after consumption of these products. A transient but significant increase in serum alanine aminotransferase activity (hepatic disturbance marker) was observed immediately after ingestion of PtW. Data for serum and urine Pt quantitation appeared to suggest that Pt nanocolloid was scarecely absorbed, although the extent of absorption could not be evaluated due to the absence in the corresponding samples of Pt with concentrations beyond the determination limit. In consideration of these results, we point out the possibility that a trace amout of Pt nanocolloid particles in PtW was absorbed into the blood causing some pathological changes in hepatic functions.

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