Metal ions are essential cofactors for a wealth of biological processes, including oxidative phosphorylation, gene regulation and free-radical homeostasis. Failure to maintain appropriate levels of metal ions in humans is a feature of hereditary haemochromatosis, disorders of metal-ion deficiency, and certain neurodegenerative diseases. Despite their pivotal physiological roles, however, there is no molecular information on how metal ions are actively absorbed by mammalian cells. We have now identified a new metal-ion transporter in the rat, DCT1, which has an unusually broad substrate range that includes Fe2+, Zn2+, Mn2+, Co2+, Cd2+, Cu2+, Ni2+ and Pb2+. DCT1 mediates active transport that is proton-coupled and depends on the cell membrane potential. It is a 561-amino-acid protein with 12 putative membrane-spanning domains and is ubiquitously expressed, most notably in the proximal duodenum. DCT1 is upregulated by dietary iron deficiency, and may represent a key mediator of intestinal iron absorption. DCT1 is a member of the 'natural-resistance-associated macrophage protein' (Nramp) family and thus its properties provide insight into how these proteins confer resistance to pathogens.

Cloning and characterization of a mammalian proton-coupled metal-ion transporter

Nutrition is one of the main regulators of circulating IGF-I. In humans, serum IGF-I concentrations are markedly lowered by energy and/or protein deprivation. Both energy and proteins are critical in the regulation of serum IGF-I concentrations. Indeed, after fasting, optimal intake of both energy and protein is necessary for the rapid restoration of circulating IGF-I. We believe, however, that in adult humans energy may be somewhat more important than protein in this regard. While the lowest protein intake is able to increase IGF-I in the presence of adequate energy, there is a threshold energy requirement below which optimal protein intake fails to raise IGF-I after fasting. When energy intake is severely reduced, the carbohydrate content of the diet is a major determinant of responsiveness of IGF-I to GH. The essential amino acid content of the diet is also critical for the optimal restoration of IGF-I after fasting, when protein intake is reduced. The exquisite sensitivity of circulating IGF-I to nutrients, the nycthemeral stability of its concentrations and its relative short half-life constitute the basis for its use as a marker of both nutritional status and adequacy of nutritional rehabilitation. For these indications, IGF-I measurement is more sensitive and more specific than measurement of the other nutrient-related serum proteins (albumin, prealbumin, transferrin, retinol-binding protein). Animal models have been developed to investigate the mechanisms responsible for the nutritional regulation of IGF-I. There is no doubt that many mechanisms are involved (Fig. 12). Decline of serum IGF-I in dietary restriction is independent of the diet-induced alterations in pituitary GH secretion. The role of the liver GH receptors is dependent on the severity of the nutritional insult. In severe dietary restriction (fasting), a marked decrease of the number of somatogenic receptors supports the role of a receptor defect in the decline of circulating IGF-I. In contrast, in less severe forms of dietary restriction (protein restriction), the decline of IGF-I results from a postreceptor defect in the GH action at the hepatic level. Nutritional deprivation decreases hepatic IGF-I production by diminishing IGF-I gene expression. Decline in IGF-I gene expression is mainly caused by nutrient deficiency and less importantly by the nutritionally induced hormonal changes (insulin and T3). Diet restriction also increases the clearance and degradation of serum IGF-I through changes in the levels of circulating IGFBPs.(ABSTRACT TRUNCATED AT 400 WORDS)

Nutritional Regulation of the Insulin-Like Growth Factors*

http://capridairyworld.org/files/pdf/RUMIN-physico-chem-published.pdf

Physico-chemical characteristics of goat and sheep milk

https://www.cell.com/cell/pdf/S0092-8674(07)00962-2.pdf

Estrogen Prevents Bone Loss via Estrogen Receptor α and Induction of Fas Ligand in Osteoclasts

Nutritional and physiologic significance of human milk proteins

A casein phosphopeptide (CPP) was prepared from beta-casein of cow's milk and the effect of this peptide on the absorption of calcium from a ligated segment of rat small intestine was investigated. CPP injected into a ligated loop of rat small intestine enhanced absorption of calcium from the loop and augmented the deposition of calcium in the femur. Furthermore, CPP inhibited the precipitation of calcium phosphate in vitro, suggesting that this peptide enhances calcium absorption from the small intestinal lumen by increasing the concentration of soluble calcium. This new evidence confirms our previous hypothesis that CPP is an important factor in raising the availability of calcium in milk.

https://www.jstage.jst.go.jp/article/jnsv1973/32/1/32_1_67/_pdf

Casein phosphopeptide (CPP) enhances calcium absorption from the ligated segment of rat small intestine

1. Semi-synthetic diets containing 200 g protein/kg were meal-fed for 1.5 h to groups of rats. The contents of the whole small intestinal tract were collected and the amount of soluble calcium was determined. 2. In the rats given 200 g casein/kg diet, formation of a fraction containing macrophosphopeptide in the small intestine was confirmed by gelfitration of the intestinal contents on Sephadex G-25. However, this macrophosphopeptide fraction was not found when casein alone was fed. 3. In the intestinal contents at 2.5 h after ingestion, the amounts of both soluble Ca and phosphorus were significantly higher in rats fed the casein diet than in those fed diets containing egg albumin, isolated soya-bean protein or an amino acid mixture. However, the amount of insoluble Ca was least in rats fed the casein diet.

/pdf/phosphopeptides-and-soluble-calcium-in-the-small-intestine-17v5emhb09.pdf

Phosphopeptides and soluble calcium in the small intestine of rats given a casein diet.

1. In an attempt to investigate calcium absorption in the rat during the postprandial period, with the least alteration of the physical environment, the undisturbed small intestine was ligated in situ 2.5 or 3.0 h after ingestion of a diet containing 200 g casein/kg or an equivalent amino acid mixture, or 925 g casein/kg. Estimation of Ca absorption was made by comparing the amount of soluble 40Ca or 45Ca in the contents of segments from the rats receiving 45Ca by intubation 30 min after withdrawal of food, ligated after a further 30 min, then killed after 0 or 30 min. 2. Under conditions such that the estimated amount of a marker, polyethylene glycol, in segments ligated in a defined position was little changed in rats killed 30 min apart, the difference in the amount of soluble 40Ca was much higher in the rats fed on the basal diet containing 200 g casein/kg than in other groups. 3. This specific effect on Ca absorption, particularly in the distal portion of the small intestine, could be seen also after 45Ca was directly injected into ligated segments in situ. The amount of 45Ca in the portal blood 15 min after injection of the label was also highest in the rats given the basal diet. 4. The results were in agreement with our previous findings that the formation and accumulation of casein phosphopeptides causes an increase in the amount of soluble Ca in the distal small intestine.

/pdf/intestinal-absorption-of-calcium-in-rats-given-diets-4ekvlnm2md.pdf

Intestinal absorption of calcium in rats given diets containing casein or amino acid mixture: the role of casein phosphopeptides

Characterization of phosphopeptide derived from bovine beta-casein: an inhibitor to intra-intestinal precipitation of calcium phosphate.

“Black vomit” is a serious disease in chicks and is caused by some kinds of fish meal in the diet. However, the causative compound has not been identified. In the present study, a new substance, 2-amino-9-(4-imidazolyl)-7-azanonanoic acid, has been isolated from mackerel meal and named Gizzerosine. This compound caused severe gizzard erosion in chiks within a week when it was fed to them at the level of 2.2 ppm in the diet. Gizzerosine is produced during fish meal manufacturing by the reaction between histidine and protein in the fish meat. The discovery of Gizzerosine raises a new problem in food chemistry and animal nutrition.

Hiroshi Naito

Papers

Casein phosphopeptide (CPP) enhances calcium absorption from the ligated segment of rat small intestine

Phosphopeptides and soluble calcium in the small intestine of rats given a casein diet.

Intestinal absorption of calcium in rats given diets containing casein or amino acid mixture: the role of casein phosphopeptides

Characterization of phosphopeptide derived from bovine beta-casein: an inhibitor to intra-intestinal precipitation of calcium phosphate.

Gizzerosine, a New Toxic Substance in Fish Meal, Causes Severe Gizzard Erosion in Chicks