Selenoamino Acid Metabolism

Selenoamino acids are defined as those amino acids where selenium has been substituted for sulfur. These include selenocysteine, selenohomocysteine and selenomethionine. Selenium and sulfur are chalcogen elements that share many chemical properties and so the substitution of normal (sulfur-containing) amino acids with selenoamino acids has little effect on protein structure and function. Because higher animals have no efficient mechanism for Met synthesis, they are unable to synthesize selenomethionine de novo. Therefore most selenomethionine comes from the diet. However seleniomethionine can be incorporated into body proteins. This allows Se to be stored in the organism and reversibly released by normal metabolic processes. Ingested selenomethionine is absorbed in the small intestine via the Na+-dependent neutral amino acid transport system. Selenocysteine may also be incorporated directly into proteins (for example glutathione peroxidases, tetraiodothyronine 5’ deiodinases, thioredoxin reductases, formate dehydrogenases, glycine reductases and some hydrogenases). However, selenocyteine is not coded for directly in the genetic code. Instead, it is encoded in a special way by a UGA codon, which is normally a stop codon. The UGA codon is made to encode selenocysteine by the presence of a SECIS element (SElenoCysteine Insertion Sequence) in the mRNA. In eukaryotes, the SECIS element is in the 3’ untranslated region (3’ UTR) of the mRNA, and can direct multiple UGA codons to encode selenocysteine residues. In mammals, selenocysteine can be generated from alanine and hydrogen selenide using the enzyme selenocysteine lyase. It can also be generated from selenocystathionine via the enzyme cystathionase. Selenocystathionine can be generated from selenohomocysteine via the enzyme cystathionine-beta synthase. In mammals selenohomocysteine generated from selenomethionine metabolism can be efficiently recycled to selenomethionine. Additionally, selenomethionine from the diet can be converted to Se-adenosyl-selenomethionine and Se-adenosyl-selenohomocysteine through S-adenosylmethionine synthetase and a methyltrasferase. Se-adenosyl-selenohomocysteine can be converted to selenohomocysteine via adenosylhomocysteinase.