Page - (000213) - in Biomedical Chemistry: Current Trends and Developments

as that of selenocysteine and the other twenty amino acids. The archaea use this unusual amino acid in proteins required for energy conversion. Pyrrolysine is located in the catalytic center of the proteins carrying it and is essential for their function. The energy generation process of the archaebacteria would not work without pyrrolysine (Srinivasan, 2002). Biosynthesis of this amino acid is based on the radical S-adenosyl-L- methionine (SAM) protein PylB, which mediates a lysine mutase reaction and produces 3-methylornithine, which is then ligated to a second molecule of lysine by PylC before oxidation by PylD to produce pyrrolysine (Gaston, 2011). In addition, Sec and Pyl are often referred as the natural amino acids. Among more than 300 AA in nature, only 20 of them (α-AA) serve as building blocks of proteins. However, represented in Fig. 3.1.4 are non- protein α-AA (e.g. ornithine, citrulline, and homo-cysteine) and non-α AA (e.g. taurine and β-alanine), which also play important roles in cell metabolism (Curis, 2007; Perta-Kajan, 2007; Manna, 2009). Figure 3.1.3: Biosynthesis of Sec and de novo synthesis of Cys. The complete synthesis of Sec on its tRNA in eukaryotes and archaea uses selenite and ATP are substrates for SPS2, yielding selenophosphate. This interacts with SecS and the intermediate, likely dehydroalanine, is used to generate SectRNA[Ser]Sec (shown on the right in the upper pathway). In the lower pathway, the de novo synthesis of Cys is shown in mammals, where sulfide and ATP are substrates for SPS2 and yield thiophosphate, which interacts with SecS and yields Cys-tRNA[Ser]Se from the SecS