Iron is essential for a variety of cellular functions, but it can cause tissue damage when present in excess. Due to its dual nature, the amount of iron in the body should be strictly controlled. One of the key molecules for maintaining iron homeostasis in the body is hepcidin, a peptide hormone mainly produced in the liver. Expression of hepcidin is upregulated by iron loading and inflammatory cytokines such as interleukin-6, and down-regulated by hypoxia and erythropoietic stimuli. Hepcidin decreases both iron absorption from the intestine and iron release from macrophages through down-regulation of ferroportin, the only iron exporter of the cells. HFE , TFR2 (transferrin receptor 2) and HJV (hemojuvelin) are expressed in the liver, and these are related to the iron sensing machinery. Mutations of one of these genes or HAMP (hepcidin) gene cause down-regulation of hepcidin expression, resulting in increased iron absorption from the intestine and iron accumulation in the body (hereditary hemochromatosis). In contrast, mutations of TMPRSS6 (matriptase-2) gene cause an increase of hepcidin expression, resulting in hereditary iron deficiency anemia. Hepcidin is also upregulated in chronic inflammation, causing anemia of chronic disease. In this review, I will attempt to provide an integrated view of physiology and pathophysiology of iron metabolism in the body by focusing on hepcidin.

Zinc plays an essential role in human physiology. It is required for numerous proteins for structural integrity, hundreds of enzymes for catalytic function and a number of biological processes for cellular metabolism. Intracellular zinc homeostasis is maintained in a remarkable regulation system mediated by zinc influx, efflux or intracellular storage/trafficking. The discovery of zinc transporters has contributed significantly to understanding the regulation and lead to new insight on zinc biology. This article reviews the recent progress in physiological and functional properties of zinc transporters, and discusses future perspectives based on current data.

There are only a few data which have been reported concerning the dietary intake of biotin in the Japanese population. The biotin intake in the adults was 29.833.3 g/day in a geometric mean by Duplicate Meals and 54.3 μg/day in an arithmetical mean after re-analysis. We also developed the new dietary survey Food Groups Calculation Study. Biotin intakes estimated by Food Groups Calculation Study (18 food groups) was 109.8 μg/day for men and 92.3 μg/day for women. However, the biotin intakes using Food Groups Calculation Study (98 food group) was 54.5 μg/day for adults. Total Diet Study gives the result of 50.7 μg/day. From these findings, it is suggested that the estimated daily intake of biotin for adults is 50 μg/day by these dietary surveys in Japan.

Selenium, an essential trace element, is incorporated in the form of selenocysteine in selenoproteins. In mammals, inorganic and organic selenium compounds are the 2 sources of selenium. Generally, organic selenium compounds, such as selenocysteine and selenomethionine, are the main selenium sources. These selenoamino acids are obtained from the diet, which contains selenium-containing proteins, and absorbed by duodenum. Then, these selenoamino acids enter the blood through the duodenal capillaries. On the other hand, selenite, an inorganic selenium compound, is taken up by red blood cells (RBCs). However, the relation between organic selenium compounds and their uptake by RBCs is not yet examined. In this study, we showed that selenocysteine is taken up by RBCs. We also showed that selenide, which is produced by the reduction of selenite, binds to hemoglobin.

We constructed the Glu219Ala/Asp225Ala serine racemase (E219A/D225A SerR) by site-directed mutagenesis, and compared the effects of Mg²⁺ on the catalytic efficiency and the structure with those of the wild-type protein. The studies on the effects of Mg²⁺ on both enzyme activities in the Glu219Ala/Asp225Ala SerR revealed that the catalytic efficiencies (kcat/Km) of both serine racemase and dehydratase reactions in the E219A/D225A SerR were not affected by the addition of 1 mM Mg²⁺, and Glu219 and Asp225 of the SerR are the essential amino acids residues for Mg²⁺ to affect both enzyme activities. Therefore, these amino acids residues are important for the SerR to form the Mg²⁺-binding site. Judging from the difference of the Keq values between the E219A/D225A SerR and the SerR, Mg²⁺ might effect on the equilibrium states in the racemase reaction. The fluorescence quenching analysis of the E219A/D225A SerR showed that Mg²⁺ probably bound to Glu219 and Asp 225 of the SerR causes a structural change in the ternary structure of the SerR, and this is one of the reasons for Mg²⁺ to increase a serine racemase activity and decrease a serine dehydratase activity of the SerR.

We previously prepared a new oyster extract (NWZ) from a mixture (WZ) of a hot water extract and a zinc-rich fraction obtained from oysters. In the present study, the availability of NWZ was investigated in comparison with WZ and zinc sulfate. Serum zinc concentration after a single oral zinc administration in rats was examined. Prior to the start of the experiment, ten-week-old male Wistar rats were given a zinc-deficient diet for 6 days. The rats were orally administered zinc-deficient diet suspension or one of three experimental diet suspensions containing two types of oyster extracts (NWZ and WZ) or zinc sulfate. A blood sample was taken from the caudal vein before and 1, 2 and 4 hours after the oral administration. Two hours after administration, rats that received the diet suspension containing zinc as NWZ or WZ showed a higher serum zinc concentration than those administered the diet suspension containing zinc as zinc sulfate. The area under the curve at 4 hours (AUC4) calculated from the serum zinc concentration after oral administration of NWZ was larger than that of those administered WZ or zinc sulfate. It is possible that zinc in NWZ is more absorbable in the gastrointestinal tract than the zinc in WZ or zinc sulfate. The effects of differences in zinc source on the absorption and tissue distribution of zinc were examined in rats fed a diet containing various concentrations of sodium phytate. Five -week-old male Wistar rats were given 0, 0.2 or 0.5 % sodium phytate-supplemented diets containing 20 ppm of zinc as NWZ or zinc sulfate for 29 days. The rats fed a diet higher in sodium phytate showed lower tissue zinc concentrations in the liver, kidney and tibia. The zinc concentrations in those tissues responded to a decrease in dietary sodium phytate. Differences in dietary zinc source (NWZ or zinc sulfate) did not significantly influence zinc concentrations in serum or various other tissues in rats receiving equal sodium phytate concentrations. The regression line between sodium phytate in the diet and tibial zinc concentration, the slope was obviously more gradual for rats receiving a diet containing zinc as NWZ than in those receiving zinc sulfate. It is possible that the zinc in NWZ is more resistant to the influence of sodium phytate. Zinc solubility was evaluated by pepsin-trypsin digestion in vitro . Zinc in NWZ diet showed higher solubility than WZ or zinc sulfate diet in pepsin-trypsin digestion. Therefore, zinc in NWZ showed higher absorbability from the gastrointestinal tract than WZ or zinc sulfate. These findings suggest that NWZ has higher zinc bioavailability than WZ or zinc sulfate.

There are many studies that maternal exposure to under nutrition in early gestation induced adult obesity.

We examined the influence of the dietary restriction in the early gestation period. Control group was permitted free access to food throughout the gestation and lactation period. Early dietary restricted group was permitted to intake 50% of the consumption had by the control group during early gestation. And, the dams were allowed to eat ad libitum during lactation period. It was found that the body weights of early dietary restricted pups were significantly higher than those of the control pups during late lactation period. So, milk yields of both groups were examined. As a result milk yields of the early dietary restricted dams were tended to lower than those of the control dams during late lactation period. To solve this discrepancy the nutritional components of both milks were compared. However there was no difference in the nutritional component of milk between the control group and early dietary restriction group. There were no association between remarkable growth in pups and nutritional component of milk. We need to seek for the other factor.

To estimate trace mineral intake in Japanese infants dependent to commercial baby foods and human milk, 53 commercial baby food samples (24 samples were for 7 or more mo baby and 29 samples were for 9 or more mo baby) were collected and their iron (Fe), zinc (Zn), copper (Cu), manganese (Mn), selenium (Se) and molybdenum (Mo) concentrations were determined by atomic absorption spectrometry (Fe, Zn, Cu and Mn) or inductively coupled plasma mass spectrometry (Se and Mo). Trace mineral concentrations in baby foods for 7 or more mo baby and 9 or more baby were as follows, respectively (mean SD) : Fe (mg/kcal), 2.36 0.98 and 3.48 3.21 ; Zn (mg/kcal), 2.00 0.93 and 2.37 1.12 ; Cu (mg/kcal), 0.44 0.13 and 0.54 0.31 ; Mn (mg/kcal), 1.03 0.51 and 1.16 0.49 ; Se (μg/kcal), 22.9 21.4 and 15.8 9.1 ; Mo (μg/kcal), 36.6 29.4 and 36.0 30.1. Trace mineral intakes in 6 to 8 mo infants and 9 to 11 mo infants dependent to human milk and commercial baby foods were estimated to be as follows, respectively : Fe (mg/d) 0.66 and 1.76 ; Zn (mg/d), 1.44 and 1.89 ; Cu (mg/d), 0.29 and 0.41 ; Mn (mg/d), 0.17 and 0.64 ; Se (μg/d), 14.1 and 14.9 ; Mo (μg/d), 8.1 and 17.7.

The seeds of Karin (Chaenomelese sinensis), usually not eaten and discarded, are surrounded with transparent mucilage, which appears readily extractable with water to give hydrocolloidal transparent solution. The structural feature of seed-surface mucilage of Karin was investigated by chemical and enzymic studies ; it contains an acidic polysaccharide, i.e., O-2-substituted d-glucurono- l-arabino-(1→4) β- d-xylan. This unique seed-surface mucilage may be constructed with the above acidic polysaccharide and d-xylo (1→4)- β- d-glucan. These two heteropolysaccharides must be associated by intermolecular hydrogen bonding to provide the interesting thixotropic characteristics with unique water-holding capabilities, appreciable as food additives and cosmetic utilization, such as skin-care lotion.

Prooxidant action of aloe-emodin the principal anthraquinone compound in Aloe vera was analyzed in permeabilized yeast cells. Aloe-emodin inactivated aconitase, the most sensitive enzyme to reactive oxygen species (ROS), in the presence of NADPH or NADH, implying that reduction of oxygen molecule was initiated by the aloe-emodin-reducing enzyme (s) with NAD (P) H as the coenzymes. Requirement of KCN, an inhibitor of cytochrome c oxidase suggests that principal reactive oxygen species produced by aloe-emodin is superoxide. Aloe-emodin may cause cellular toxicity induced by mitochondorial oxidative damage through the inactivation of aconitase, a key enzyme of mitochondrial energy production.

The purpose of this study is to clarify the regional differences in biotin contents in foods between Japan, America, Canada, German, and Denmark by comparing the published data. There was a positive correlation in meat group and egg group between Japan and Western countries. But, in vegetable group a positive correlation was not observed. The possible reason might be that biotin biosynthesis in vegetables is different between Japan and Western countries due to differences of cultivation conditions. Then, to study the effect of cultivation conditions on biotin biosynthesis in plants, pea sprouts were hydroponically cultivated under 5 conditions (Control (C) : 22℃, 10-h light/14-h dark, Negative control (NC) : 22℃, 10-h light/14-h dark, addition of acidomycin, Short-time lighting (SL) : 22℃, 5-h light/19-h dark, No lighting (NL) : 22℃, 24-h dark, Low temperature (LT) : 4℃, 10-h light / 22℃, 14-h dark). Biotin contents in NL and LT were remarkably lower than those in C (p < 0.05). Moreover, biotin contents in SL also decreased to approximately 75 % of those in C, although statistical significance was not observed. These results strongly suggest that cultivation conditions of plants affect biotin biosynthesis, leading to the differences of biotin contents in vegetables among the regions for planting.

Dietary therapy for obesity is considered as the first-choice treatment and is at least as important as medical treatment. Various supplements, such as l-carnitine (LC), are expected to affect loss weight and are already available as supplements worldwide. However, in many cases, young people who do require losing weight also tend to intake LC supplements. In the present study, the effect of dietary LC on lipid metabolism was evaluated in growing rats. Four-week-old male Wistar rats were fed an AIN-93G modified diet containing LC (0.25 % or 1.0 %). As parameters of lipid metabolism, the relative white adipose tissue (WAT) weights, serum and liver lipid contents, lipid metabolizing enzyme activities and fatty acid related enzymes expression levels in the liver were evaluated.

Dietary LC did not affect the relative WAT weights, serum and liver lipid contents, lipid metabolizing enzyme activities or fatty acid related enzymes expression levels in the liver. However, it was confirmed that serum and liver LC contents increased following the intake of LC diets compared with a non-LC-containing diet. Therefore, the growing rats were supplemented unnecessarily with LC, which is required for the β-oxidation of fatty acid by an endogenous biosynthetic pathway. Hence, it was suggested that LC intake by young people was not required.

Beef marbling is an important trait of meat quality, which contributes directly to the value of beef especially in the Japanese market. The development of beef marbling was closely associated with an increase in the number of adipocytes, that is, adipocyte differentiation in the skeletal muscle. Peroxisome proliferator-activated receptorγ (PPARγ) is a ligand-dependent transcription factor that directly activates the expression of adipocyte-specific genes, and is universally accepted as the master regulator for adipocyte differentiation. Through screening for natural PPARγ activator in feed using the PPARγ luciferase reporter assay, the ethanol extracts of sake lees, soy sauce lees, vinegar lees, and beer lees, and soy sauce oil activated PPARγ. Treatment with the ethanol extracts of these lees materials enhanced some markers of adipocyte differentiation such as glycerol-3-phosphate dehydrogenase activity and triglyceride accumulation in 3T3-L1 cells. These results suggest that these lees materials possess PPARγ activators. Moreover, according to the results of the sequential fractionation assay, we confirmed that PPARγ-activate factors in soy sauce oil were different from linoleic acid, originated from soy bean oil.

Calcineurin (CN), also known as phosphoprotein phosphatase 2B, is a Ca²⁺/calmodulin-dependent protein serine/threonin phosphatase that plays a pivotal role in a variety of cellular functions, such as immune and nerve systems in our body. It has been shown that the phosphatase activity is stimulated by divalent ions, such as nickel (Ni²⁺) and manganese (Mn²⁺) in vitro . In the present study, we examined combined effect of Mn²⁺ and Ni²⁺ on CN activity in vitro . Although the combined effect of Mn²⁺ on Ni²⁺-stimulated CN activity was not observed, we have found that the activity was inhibited by low concentrations of Mn²⁺. To further examine effect of Mn²⁺ inhibition on Ni²⁺-stimulated phosphatase activity, we studied on this inhibition by kinetic analysis. The result showed that Mn²⁺ inhibition of Ni²⁺-stimulated CN activity was uncompetitive inhibition using Lineweaver-Burk plot. Inhibition constant (Ki) for Mn²⁺ was seen at 20.0 μmol/L.

Background - Zinc (Zn) is critical for the functional and structural integrity of cells, in which it participates in a number of processes, including gene expression. Zn deficiency has effects that resemble the symptoms of human aging, including low immunity, dermatitis, delayed wound healing, and impaired taste. In this study, we examined the effect of Zn deficiency on the expression of the aging-related gene Klotho in rats. In mice, Klotho is involved in a murine developmental syndrome that resembles human aging.

Methods - Male Sprague-Dawley rats (161162 g) were fed a diet deficient in Zn or containing 0.01 % Zn for 4 weeks. Kidneys were removed after 0, 1, 2, 3 and 4 weeks, and the expression of Klotho mRNA was determined using real-time polymerase chain reactions.

Results - Data were analyzed using the comparative threshold (CT) method. The mean ∆∆CT values for renal Klotho mRNA expression were much lower in the Zn-deficient rats than in the control rats. In the Zn-deficient group, values of ∆∆CT were 1.15 0.46 at 2 weeks, 1.69 0.33 at 3 weeks, and 2.08 0.53 at 4 weeks.

Conclusion - Zn deficiency was associated with decreased Klotho gene expression, suggesting that Zn deficiency might accelerate aging by inhibiting the expression of Klotho.

In recent years, it has been suggested that Zinc deficiency causes alteration in the biological defense system. To examine the effects of hyperbaric oxygen therapy (HBO) on the lung tissues of zinc deficiency models, zinc deficient rats were investigated morphological changes and the expression of TNF-α, Cu/Zn SOD, ED₁ and iNOS in the lung tissues by immunohistochemically after exposure to high pressure using pure oxygen. In the present study, two special diets were prepared ; a zinc deficient diet and a standard diet (0.05 % Zn). Seven weeks old SD strain rats were fed either on a Zn deficient (Zn-D, n=12) or a standard diets (Control, n=12) for 6 weeks. Six of ZnD and 6 of Control were exposed to 0.28 MPa using pure oxygen for 60 minutes in a hyperbaric chamber (ZnD-O₂ and Control-O₂). After decompression to surface, histopathological and immunohistochemical examination of lung tissues of rats in the 4 groups were carried out. Mild pathological changes such as congestion, destruction of alveoli and the appearance of inflammatory cells were seen in the ZnD-O₂. Expression of ED₁ and iNOS decreased in ZnD-O₂. Changes in the expression of TNF-a and Cu/Zn SOD did not seen in ZnD, Control-O₂, ZnD-O₂. These findings suggest that zinc deficiency reduces the threshold level of oxygen toxicity in lung tissues. These results also suggest that hyperbaric oxygen therapy causes the lung damage in patients under zinc deficiency condition. Moreover, the results in immunohistochemical study after oxygen exposure indicate that zinc deficiency causes alteration in the normal biological defense system.

The pyridoxal-5-phosphate (PLP)-dependent amino acid racemases occur in almost every bacterium but may differ considerably with respect to substrate specificity. We here isolated the cloned broad substrate specificity racemase ArgR of Pseudomonas taetrolens from Escherichia coli by classical procedures. The racemase was biochemically characterized and amongst other aspects it was confirmed that it is mostly active with lysine, arginine and ornithine, but merely weakly active with alanine, whereas the alanine racemase of the same organism studied in comparison acts on alanine only. ArgR is necessary for the catabolism of D-arginine and D-lysine by P. taetrolens.

Pheophorbide a is a catabolite of chlorophyll often found in food and supplements. Upon ingestion of pheophorbide a contained in food and subsequent exposure to sunlight, humans and animals can develop cutaneous photosensitivity. In search for photoprotective agents, we have first screened plant extracts using photo-oxidized hemolysis as an in vitro model for cutaneous photosensitivity. Thereafter, the photoprotective potential of the plant extracts was further tested in an animal model. Red blood cell suspensions from Wistar rats were exposed to visible light in the presence of pheophorbide a with or without the plant extracts. At the end of the light exposure, absorbance of the supernatants was measured and hemolysis ratios were calculated. For an animal test, the plant extracts or extraction solvent was given orally to female Wistar rats for one week prior to the light exposure. On the 8th day, after the pheophorbide a administration, the dorsal skin of rats was shaved and exposed to visual light to induce cutaneous photosensitivity. The dorsal skins were observed for redness, edema, and necrosis, and were also examined histologically. In hemolysis assays, the extract from Larix sibirica (Siberian larch) showed strong inhibitory activity. This extract was also shown to be effective in reducing the severity of the photosensitivity in rats. Furthermore, histological examination of the rats given Larix sibirica extract revealed that the inflammation remained mainly in epidermis and did not affect dermis.

A relationship between plasma concentrations of vitamin C and serum biochemical parameters related to liver diseases was examined in 48 dogs hospitalized for diagnosis and treatments of diseases including liver disturbance. Plasma concentration of vitamin C was lower in dogs exhibiting serum activity of alanine aminotransferase (ALT), a marker of leakage of liver membrane, above the reference range than in those within or below the range. Mean vitamin C concentration in plasma (5.2 mg/L), however, was not lower even in dogs with higher ALT activity, as compared with that determined in clinically normal Shiba dogs (4.99.2 mg/L). Plasma concentrations of vitamin C negatively related to activities of ALT and aspartate aminotransferase (p < 0.05). Vitamin C nutrition may worsen through decreasing synthesis of vitamin C in dogs with liver necrosis.

A plant-based diet is thought to be better for the prevention and treatment of lifestyle-related diseases. A plant-based extract fermented by lactic acid bacteria and yeast (PELY) was made from various plant materials and was fermented product applying to traditional food-preservation technique, that is, fermentation and sugaring. In this study, the characterization and physiological function of PELY were examined.

PELY contained 58.8 % carbohydrate, 3.7 % protein, and 1.3 % lipid. It contained 18 kinds of amino acids and vitamin A, B₁, B₂, B₆, B₁₂, E, K, niacin, pantothenic acid, and folic acid. It also did a lot of dietary fiber and phytochemicals (polyphenol, terpenoid, i.e.).

Moreover, it was determined that PELY had several physiological functions such as antioxidant, antihypertensive, antibacterial, prompt digestive and anti-tyrosinase activities. As the results, PELY possessed antioxidant, antihypertensive, antibacterial, and anti-tyrosinase activities in vitro.

This study was undertaken to investigate to the effects of goat milk supplementation on plasma calcium contents, bone mineral density and bone mineral content of total femur in rats. Six-week-old male Sprague-Dawley rats were randomly assigned to 3 groups for 10 weeks. The experimental groups were divided 3 groups ; C group (distilled water), M group (cow milk), G group (goat milk). There were no significant differences in body weight gain and plasma calcium contents, BMD, BMC among the groups. These results suggest that reliable goat milk data in not commonly consumed food in Korea for the nutritional information and food composition database.

We examined the clinical effects of a new type of oyster extract with a zinc concentration three times higher than that of a previously tested sample (made by Japan Clinic Co., Ltd.) on 4 depressed patients and 6 normal control subjects. Doses of up to 3 tablets of this new oyster extract were administered to depressed patients for 6 to 10 days with or without antidepressants. We found that the clinical effects of the new oyster extract were almost the same as those of the previous one. However, from a clinical point of view, the fact that the new oyster extract requires smaller doses has an economic benefit. The zinc component of oyster extract is considered to play a major role in improving depression.