This book is one of our contemporary medical bibles. It needs no introduction; those who have frequent need of it know it very well, and those who use it less often seek it out on the library shelf when problems arise. The book is truly encyclopedic. Everything relevant discovered during the six-year intervals between publication finds its way into these pages. By today's standards, its 1,778 closely packed small-print pages are a bargain. The mutant gene is both hero and villain in this book. It is reponsible for the biochemical abnormality that results in disease, no matter how rare a given abnormality may be. By the same token, however, it is truly an experiment of nature, shedding light on fundamental metabolic sequences and biologic mechanisms. This volume, more than most, explains the contributions of the laboratory to clinical medicine. Each chapter seems to have been rewritten, so that the exciting

The Metabolic Basis Of Inherited Disease.

The requirement of the trace element selenium for life and its beneficial role in human health has been known for several decades. This is attributed to low molecular weight selenium compounds, as well as to its presence within at least 25 proteins, named selenoproteins, in the form of the amino acid selenocysteine (Sec). Incorporation of Sec into selenoproteins employs a unique mechanism that involves decoding of the UGA codon. This process requires multiple features such as the selenocysteine insertion sequence (SECIS) element and several protein factors including a specific elongation factor EFSec and the SECIS binding protein 2, SBP2. The function of most selenoproteins is currently unknown; however, thioredoxin reductases (TrxR), glutathione peroxidases (GPx) and thyroid hormone deiodinases (DIO) are well characterised selenoproteins involved in redox regulation of intracellular signalling, redox homeostasis and thyroid hormone metabolism. Recent evidence points to a role for selenium compounds as well as selenoproteins in the prevention of some forms of cancer. A number of clinical trials are either underway or being planned to examine the effects of selenium on cancer incidence. In this review we describe some of the recent progress in our understanding of the mechanism of selenoprotein synthesis, the role of selenoproteins in human health and disease and the therapeutic potential of some of these proteins.

https://www.liebertpub.com/doi/pdf/10.1089/ars.2007.1528

From selenium to selenoproteins: Synthesis, identity, and their role in human health

Tissue-specific functions of individual glutathione peroxidases.

Guidelines for Canadian Drinking Water Quality

Food systems need to produce enough of the essential trace element Se to provide regular adult intakes of at least 40 microg/d to support the maximal expression of the Se enzymes, and perhaps as much as 300 microg/d to reduce risks of cancer. Deprivation of Se is associated with impairments in antioxidant protection, redox regulation and energy production as consequences of suboptimal expression of one or more of the Se-containing enzymes. These impairments may not cause deficiency signs in the classical sense, but instead contribute to health problems caused by physiological and environmental oxidative stresses and infections. At the same time, supranutritional intakes of Se, i.e. intakes greater than those required for selenocysteine enzyme expression, appear to reduce cancer risk. The lower, nutritional, level is greater than the typical intakes of many people in several parts of the world, and few populations have intakes approaching the latter, supranutritional, level. Accordingly, low Se status is likely to contribute to morbidity and mortality due to infectious as well as chronic diseases, and increasing Se intakes in all parts of the world can be expected to reduce cancer rates.

/pdf/selenium-in-global-food-systems-23a5koo10v.pdf

Selenium in global food systems.

The deposition of selenium (Se) in erythrocyte proteins was studied in rats fed Se as sodium selenite, selenocystine, selenomethionine (Se-Met), high Se wheat or selenium-enriched yeast. Ion-exchange chromatography of acid hydrolyzates of selenium-enriched yeast, high Se wheat and intrinsically labeled 75Se wheat indicated that the majority of the Se was present as Se-Met. Gel filtration (Sephadex G-150) of erythrocyte lysates revealed that Se was deposited mainly in two proteins, glutathione peroxidase (GPx) and hemoglobin (Hb). When selenite or selenocystine was the dietary form of Se, the majority of the erythrocyte Se was present with GPx, but when the Se was supplied from either Se-Met, yeast or wheat, it was deposited to a greater extent in Hb than GPx. Injection of 75Se as either Se-Met or selenite gave results consistent with the feeding studies. 75Se-labeled selenite injection resulted in labeling of primarily GPx, but 75Se-Met injection labeled predominantly Hb. Hence, the dietary forms of Se influence the relative distribution of Se between GPx and Hb in erythrocytes, and this may be a factor contributing to the difference between human and animal erythrocytes.

Deposition of dietary organic and inorganic selenium in rat erythrocyte proteins.

Purification and properties of selenoprotein W from rat muscle.

Weanling male rats were fed a basal selenium (Se)-deficient diet or this diet plus 2 ppm Se as either selenite, selenocystine (SeCys) or selenomethionine (SeMet) for 9 wk. The rats were killed by decapitation while anesthetized with ether, and tissues were assayed for glutathione peroxidase (GPx) and selenocysteine lyase activities, and for Se content. Dietary Se had no effect upon the activity of tissue selenocysteine lyase. This activity was highest in the liver, followed by kidney, muscle and testis in decreasing order. Although the GPx activity was lower in tissues of the Se-deficient rats, there were no significant differences in its activity between animals given the different chemical forms of dietary Se. Except for the kidney, the tissue Se concentrations were similar in rats fed selenite or SeCys, but the Se content in testis, muscle, pancreas, heart, spleen, whole blood, erythrocytes and plasma was significantly higher in rats fed SeMet than in those fed either selenite or SeCys. The greatest increase due to SeMet compared with the selenite and SeCys treatments was about 10-fold in the muscle compared with 1.3- to 3.6-fold for the other tissues.

Effects of dietary selenite, selenocystine and selenomethionine on selenocysteine lyase and glutathione peroxidase activities and on selenium levels in rat tissues.

Selenoprotein W of rat muscle binds glutathione and an unknown small molecular weight moiety.

Rat skeletal muscle selenoprotein W cDNA was isolated and sequenced. The isolation strategy involved design of degenerate PCR primers from reverse translation of a partial peptide sequence. A reverse transcription-coupled PCR product from rat muscle mRNA was used to screen a muscle cDNA library prepared from selenium-supplemented rats. The cDNA sequence confirmed the known protein primary sequence, including a selenocysteine residue encoded by TGA, and identified residues needed to complete the protein sequence. RNA folding algorithms predict a stem-loop structure in the 3' untranslated region of the selenoprotein W mRNA that resembles selenocysteine insertion sequence (SE-CIS) elements identified in other selenocysteine coding cDNAs. Dietary regulation of selenoprotein W mRNA was examined in rat muscle. Dietary selenium at 0.1 ppm as selenite increased muscle mRNA 4-fold relative to a selenium-deficient diet. Higher dietary selenium produced no further increase in mRNA levels.

https://www.pnas.org/content/pnas/92/19/8749.full.pdf

M. A. Beilstein

Papers

Deposition of dietary organic and inorganic selenium in rat erythrocyte proteins.

Purification and properties of selenoprotein W from rat muscle.

Effects of dietary selenite, selenocystine and selenomethionine on selenocysteine lyase and glutathione peroxidase activities and on selenium levels in rat tissues.

Selenoprotein W of rat muscle binds glutathione and an unknown small molecular weight moiety.

Rat skeletal muscle selenoprotein W: cDNA clone and mRNA modulation by dietary selenium