Selenium-Containing Enzymes

All selenium-containing proteins and enzymes in animals, microorganisms and plants incorporate selenocysteine non-specifically105 or as part of Se-dependent antioxidant enzymes such as glutathione peroxidase, (EC 1.11.1.9) which has a Se-cysteine residue in its active site.116 120 An active form of Se, selenophosphate, is produced by selenophosphate synthetase in several bacteria. This active form is required for the production of Secys-tRNA, a precursor for Se-cysteine.121 In a similar vein, a Se-containing modified-tRNA nucleoside, 5-methylaminomethyl-2-selenouridine, encodes a selenouridine synthase which replaces sulfur in tRNA with selenium.122... 

Mammalian thioredoxin reductases are a family of selenium-containing pyridine nucleotide-disulfide oxidoreductases. These enzymes catalyze NADPH-dependent reduction of the redox protein thioredoxin (Trx), which contains a redox-active disulfide and dithiol group and by itself may function as an efficient cytosolic antioxidant [77]. One of the functions of Trx/ thioredoxin reductase system is the NADPH-catalyzed reduction of protein disulfide [78] ... 

To prevent membrane damage, the red cell has an armoury of antioxidants, notably a manganese or selenium containing enzyme called superoxide dismutase (SOD) and the sulfydryl compound glutathione (GSH), a tripeptide of y-glutamate, cysteine and glycine. 

Table 1 Selenium-containing enzymes in prokaryotes (Eubacteria and Archaea)...

Glutathione peroxide was the first selenium-containing mammalian enzyme identified over 35 years ago," the same year that the selenoprotein A was identified in C. sticklandtL With the advent of the human genome sequence we now know that there are 25 selenoproteins encoded in humans, " with similar numbers encoded by other mammals. Some of the best-studied selenoproteins include five isoenzymes of thioredoxin reductase, three... 

The first biochemical analysis of a selenium-containing XDH was reported in 1999 by Andreesen s group. This preparation was specific for xanthine and did not hydroxylate nicotinic acid. Moreover, the enzyme contained FAD, acid-labile sulfur, iron, and a dinucleotide molybdenum cofactor. Most intriguing was the near-equimolar presence of tungsten and molybdenum. It should be noted that the culture medium contained nearly equimolar levels of these metals, making one wonder whether the specificity of this enzyme for metal may be relaxed (i.e., can use Mo or W). Selenium was also found in the preparation and could be released by treatment with cyanide indicating it was also a labile cofactor. This further confirmed the chemical nature of the cofactor from the NAH enzyme from the same strain. ... 

Another selenium-containing molybdenum hydroxylase that has been isolated from Clostridium barkeri (identical to Eubacterium barkeri) is nicotinic acid hydroxylase (NAH). Clostridium barkeri was isolated initially as a fermentor of nicotinic acid and thus NAH is a key enzyme in the efficient fermentation of nicotinic acid as a source of carbon and energy. NAH contained selenium when purified from cells labeled with Se-selenite. However, this label was lost during denaturing gel electrophoresis and also on heating of the enzyme (Dilworth 1982). Exhaustive analysis of selenium-labeled alkylation products of NAH under various conditions revealed selenium was bound as a labile cofactor (Dilworth 1982), and not as seleno-cysteine. This report was the first to describe a selenium-dependent enzyme that did not contain selenium in the form of selenocysteine. 

Selenium is a trace element essential to life. For example, the selenium-containing enzyme glutathione peroxidase catalyzes the destruction of peroxides (ROOH) that are harmful to cells. Conversely, at high concentration, selenium can be toxic. 

This enzyme also contains an N-terminal pyruvoyl residue as does one subunit of a selenium-containing glycine reductase which utilizes a dithiol to convert glycine into acetate with coupled formation of ATP ... 

In some mixed acid fermentations (e.g., that of Shigella) formic acid accumulates, but in other cases (e.g., with E. coli at pH 6) it is converted to C02 and H2 (Eq. 17-25). The equilibration of formic acid with C02 and hydrogen is catalyzed by the formic hydrogen-lyase system which consists of two iron-sulfur enzymes. The selenium-containing formate dehydrogenase (Eq. 16-63) catalyzes oxidation of... 

There were 37 distinct enzymes that contain molybdenum or tungsten known by the end of 1997. The enzymes are diverse in function, broadly distributed, and include oxidases, reductases, dehydrogenases, a transhydroxylase, and a hydratase. The Mo enzymes are found in eubacteria, archae, protista, fungi, plants, and animals (including humans) and are essential for respiration and carbon and nitrogen assimilation. Several of the enzymatic substrates and products are key components in the nitrogen, sulfur, selenium, carbon, and arsenic cycles and have major biological and environmental impact. 

Glutathione peroxidase is a selenium-containing enzyme. A special form of peroxidase is catalse, an enzyme with one of the highest known turnover numbers... 

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