Phosphoserine, biosynthesis

With regard to selenocysteine biosynthesis in archaea and eukarya, a tRNA has been known for some time, which accepts L-serine and possesses an anticodon complementary to UGA. It shares a number of structural featmes with tRNA from E. coli, such as extended aminoacyl acceptor and D-arms. In eukarya, the serine residue attached to this tRNA can be phosphorylated by a specific kinase and it was first assumed that this tRNA inserts phosphoserine into proteins. However, closer examination revealed that this tRNA carries selenocysteine in vivo and certainly is the pendant to tRNA from E. coli. It is still elusive whether (9-phosphoseryl-tRNA is the biosynthetic intermediate for selenocysteyl-tRNA formation in eukaryotes also, there is no evidence yet of an eukaryal and archaeal enzyme, equivalent in its function to selenocysteine synthase from bacteria. 

Many methanogenic archaeabacteria lack cysteinyl-tRNA synthetase (CysRS). Interestingly, a Class II enzyme called O-phosphoseryl-tRNA synthetase (SepRS) acylates tRNA with O-phosphoserine (Sep) to form Sep-tRNA , which is then converted to Cys-tRNA by the enzyme Sep-tRNA Cys-tRNA synthase (SepCysS). It has been proposed that this indirect pathway may be the sole route for cysteine biosynthesis in these organisms (9). The crystal structure of SepRS was recently... 

There is increasing evidence in the literature that amino acid sequences with phosphoserine adjacent to a dicarboxylic acid recur systematically in phosphoproteins. It, therefore, seems probable that certain principles must exist which determine the biosynthesis of such amino acid sequences and their subsequent incorporation into the protein molecule. 

In the biosynthesis of serine from glucose, 3-phosphoglycerate is first oxidized to a 2-keto compound (3-phosphohydroxypyruvate), which is then transaminated to form phosphoserine (Fig. 39.5). Phosphoserine phosphatase removes the phosphate, forming serine. The major sites of serine synthesis are the liver and kidney. 

It is clearly not possible to discuss here at any length, the metabolism of individual amino acids. In addition, the details of the biosynthesis and catabolism of amino acids, well reviewed in Volume II of Meister s recent book , are concerned more with the formation and breakdown of the carbon skeleton than with the introduction or loss of the amino group. Modifications of some of the twenty amino cicids normally found in proteins have been detected in some protein hydrolysates, e.g. iodinated tyrosine, phosphoserine and hydroxylysine. In some cases the modification appears to be made before the amino acid is incorporated into protein (e.g. iodination of tyrosine) while in other cases modification is believed to occur when the amino acid is already present in proteins (e.g. hydroxylation of lysine, and in some cases, of... 

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