Selenium and Glutathione

The chemistry of selenium resembles that of sulfur. Inorganic forms of sulfur include hydrogen sulfide HjS), sulfite fSOj ), and sulfate (SO ). The corresponding forms of selenium are hydrogen selenide (H2Se), selenite (ScO, )- 3 d selenate (SeO ). Cysteine is the most well known organic form of sulfur. The corresponding selenium derivative is selenocysteine. 

Irtcorporatlon of Amirte Acida Imo tha Crowing PolvpaptMa Chain 

FIGURE 10-55 Typical pathway for incorporation of an amino acid into a growing polypeptide chain top). Pathway used for the incoiporation of selenocysteine into a growing polypeptide chain ibcltcim). 

Selenium-requiring proteins indude GSH peroxidase, deiodinase, selenoprotein P, and selenoprotein W, GSH peroxidase is vital for the removal of certain forms of toxic oxygen, i.o, lipid peroxidides and hydrogen peroxide. 5 -Deiodinase is used for the synthesis of thyroid hormone. The functions of selenoproteins P and W are not known, 

The various deiodinases respond in different ways to selenium deficiency. Studies with rats revealed that nutritional Sc deficiency results in a decline in activity of the type I enzyme in the liver and kidney with little effect on the type 1 activity in the thyroid gland, and with little effect on the type II and type III enzymes in the brain (Pallud, 1997). 

Incorporation of Amino Acids into the Growing Polypeptide chain 

---

There is very little evidence relating to the role of ROMs in cholestatic liver disease. Serum selenium and glutathione peroxidase activity are decreased in humans with intrahepatic cholestasis of pregnancy (Kauppila et al., 1987). Low levels of vitamin E have been reported in patients with primary biliary cirrhosis, and in children with Alagille s syndrome or biliary atresia (Knight et al., 1986 Jeffrey etal., 1987 Lemonnier etal., 1987 Babin etal., 1988 Kaplan et al., 1988 Sokol etal., 1989). Serum levels of Mn-SOD are increased in patients with all stages of primary biliary cirrhosis compared with patients with other forms of chronic liver disease, although whether this causes or results from the disease process is unclear (Ono etal., 1991). 

Swanson AB, Wagner PA, Ganther HE, et al. 1974. Antagonistic effects of silver and tri-o-cresyl phosphate on selenium and glutathione peroxidase in rat liver and erythrocytes [Abstract], Fed Proc... 

Waschulewski, I.H. and Sunde, R.A. 1988. Effect of dietary methionine on tissue selenium and glutathione peroxidase on tissue selenium and glutathione peroxidase (EC 1.11.1.9) activity given selenomethionine. Br. J. Nutr. 60, 57-68. 

Glutathione is discussed further in the section on selenium and glutathione in Chapter 10. The enzyme assay is conducted using glutathione reductase extracted from red blood cells with and without added FAD. Chmnic consumption of a diet deficient in riboflavin allows the continued synthesis of a variety of flavoproteins, but results in the accumulation of apoenzyme without its conversion to holoen-zyme. Addition of chemically pure FAD to a biological fluid containing apoenzyme results In the stimulation of enzyme activity because of the formation of the holoenzyme. It is this stimulation of enzyme activity that is used to determine vitamin status in humans. 

Thomas AG, Miller V, Shenkin A, Fell GS, Taylor F. Selenium and glutathione peroxidase status in paediatric health and gastrointestinal disease. J Pediatr Gastroenterol Nutr 1994 19 213-9. 

In macaques that were orally administered doses of 0.025-0.3 mg selenium/kg as L-selenomethionine for up to 30 days, both erythrocyte selenium and glutathione peroxidase-specific activity showed a delay before increasing in a dose-related manner (Hawkes et al. 1992). At 0.15 and 0.3 mg selenium/kg, glutathione peroxidase-specific activity in erythrocytes continued to increase for 15 days after cessation of treatment and remained elevated through the end of the study (40 days after the end of treatment). The investigators attributed this effect to an initial deposition of selenium into a nonspecific pool (such as substitution for methionine in serum proteins), followed by slow release into the erythrocyte. Wistar rats also show incorporation of selenomethionine into proteins (Behne et al. 1991). 

Beilstein MA, Whanger PD. 1983. Distribution of selenium and glutathione peroxidase in blood fractions from humans, rhesus and squirrel monkeys, rats and sheep. J Nutr 113 2138-2146. 

HojoY. 1987. Selenium and glutathione peroxidase in human saliva and other human body fluids. Sci Total Environ 65 85-94. 

Rudolph N, Wong SL. 1978. Selenium and glutathione peroxidase activity in maternal and cord plasma and cells. PediatrRes 12 789-792. 

Yin SA, Sato I, Hosokawa Y, et al. 1991. The necessity of dietary vitamin B6 to selenium biopotency for tissue selenium and glutathione peroxidase in rats. J Nutr Sci Vitaminol (Tokyo) 37(5) 509-516. 

Zachara BA, Wardak C, Didkowski W, et al. 1993. Changes in blood selenium and glutathione concentrations and glutathione peroxidase activity in human pregnancy. Gynecol Obstet Invest 35(1) 12-17. 

Wilson DC, Tubman R, Bell N, et al. 1991. Plasma manganese, selenium and glutathione peroxidase levels in the mother and newborn infant. Early Hum Dev 26 223-226. 

Molin, M. Bergman. B. Marklund, S.L., Schutz, A. and Skerfving, S. (1990a) Mercury, selenium, and glutathione peroxidase before and after amalgam removal in man. Acta Odont. Scand.. 48.189.202. 

Spallholz, J.E. 1988. Selenium and glutathione peroxidase essential nutrient and antioxidant component of the immune system, in Antioxidant Nutrients and Immune Functions, Phillips, M. and Tengerdy, R.P., Eds., Plenum Press, New York, 145. 

Prohaska, J. R., Mowafy, M., and Ganther, H. E., 1977, Interactions between cadmium, selenium and glutathione peroxidase in rat testis, Chem. Biol. Int. 18 253. 

Canther, H. E., et a/., "Selenium and Glutathione Peroxidase in Health and Disease—A Review," Trace Elements in Human Health and Disease, edited by A. S. Prasad and D. Oberleas, Academic Press, Inc., New York, N.Y., 1976, p. 205. 

---