Amino acid activation and

AMINO ACID ACTIVATION AND CODON TRANSLATION BY tRNAs... 

Why does mtDNA contain any protein genes, or why does mtDNA even exist It seems remarkable that the cells of our bodies make the 100 or so extra proteins (encoded in the nucleus) needed for replication, transcription, amino acid activation, and mitochondrial ribosome formation and bring these into the mitochondria for the sole purpose of permitting the synthesis there of 13 proteins. The explanation is not evident. What are the 13 proteins ... 

T Stein, J Vater. Amino acid activation and polymerization at modular multienzymes in nonribosomal peptide biosynthesis. Amino Acids 10 201-227, 1996. 

Among activated forms of amino acids, mixed anhydrides with inorganic phosphate or phosphate esters require a special discussion because they are universally involved in peptide biosynthesis through the ribosomal and non-ribosomal pathways. These mixed anhydrides have stimulated studies in prebiotic chemistry very early in the history of this field. Amino acyl adenylates 18c have been shown to polymerize in solution [159,160] and in the presence of clays [139]. However, their participation as major activated amino acid species to the prebiotic formation of peptides from amino acids is unlikely for at least two reasons. Firstly, amino acid adenylates that have a significant lifetime in aqueous solution become very unstable as soon as either CO2 or bicarbonate is present at millimolar concentration [137]. Lacey and coworkers [161] were therefore conduced to consider that CO2 was absent in the primitive atmosphere for aminoacyl adenylate to have a sufficient lifetime and then to allow for the emergence of the modern process of amino acid activation and of the translation apparatus. But this proposition is unlikely, as shown by the analysis of geological records in favor of CO2 contents in the atmosphere higher than present levels [128]. It is also in contradiction with most studies of the evolution of the atmosphere of telluric planets [30,32], Secondly, there is no prebiotic pathway available for adenylate formation and ATP proved to be inefficient in this reaction [162]. 

The imidazole hydroxyl SC linker 1.30 (87) linked to hydrophilic PS resins has been employed for loading acids and C-terminal Fmoc-protected amino acids. Activation and deprotection of functional groups is performed by TFA treatment, which produces the imidazole TFA salt. The imidazole ring intramolecularly attacks the ester bond upon neutralization at pH 7 with aqueous buffer and releases the compound as the free acid into solution. 

Fig. 11. Reaction scheme for (I) substrate amino acid activations and dipeptide formation, (II) racemization, and (III) N-methylation. J and E2 are symbols for enzyme activities (from peptide synthetase modules) either on the same or separate proteins. R1 and R2 are amino acid side chains, where R1 is part of the first amino acid activated by the peptide synthetase indicates the linkage between 4 -phosphopantetheinylated enzyme and the substrate or peptide intermediate. AdoMet, S-adenosylmethionine AdoHcy, S-adenosylhomocysteine...

The CCA terminus containing the amino acid attachment site extends from one end of the L. This single-stranded region can change conformation during amino acid activation and protein synthesis. 

T. Pederson, 50 years ago protein synthesis met molecular biology the discoveries of amino-acid activation and transfer RNA, FASEB J. 2005, 19, 1583. 

In the living cell, amino acid activation and binding to tRNA probably occurs in a single step, catalyzed by a single macromolecular complex. But, for the sake of clarity, amino acid activation is described as a separate event. 

A theory proposing that the effect of steroids is to stimulate amino acid activation and, as a result, protein synthesis is not without objections. If the primary effect of steroid hormones is to activate amino acids, the rate of synthesis of all proteins should be increased in the target organ. In contrast, steroids stimulate the biosynthesis of highly specific proteins, and therefore it seems more logical to assume that the steroids act at a step of the biosynthetic pathway that determines the specificity of the proteins synthesized. Such a mechanism could involve transcription of messenger RNA on DNA template. The rate of incorporation of labeled nucleotide triphosphate into the rapidly labeled nuclear RNA by the methods described by Weiss is markedly decreased in castrated animals. 

Secondly, one wants a structure which is a good acceptor for an acyl group but a poor one for a phosphoryl group. This could be an SH, a reactive OH, or the NH of an imidazole or amide group. Among the known vitamins and cofactors there are, of course, several with the necessary structural requirements outlined above. The first to come to mind is CoA, but so far it has not been possible to demonstrate a CoA requirement for amino acid incorporation into mammalian or plant microsomes. Nevertheless this vitamin seems to be essential for the incorporation of amino acids into the proteins of hen oviducts (56) and it does, of course, the job of displacing activated fatty acids from their activating enzymes (170). Vitamin Bi2 also fits the structural requirements and it has, indeed, been claimed to be essential for amino acid activation and subsequent incorporation into rat liver microsomes (i07, 178, 179), but this requirement has not yet been confirmed by other authors (180,181). 

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