Amino acid replacement

Humans can synthesize 12 of the 20 common amino acids from the amphiboHc intermediates of glycolysis and of the citric acid cycle (Table 28-1). While nutritionally nonessenrial, these 12 amino acids are not nonessential. AH 20 amino acids are biologically essential. Of the 12 nutritionally nonessential amino acids, nine are formed from amphibolic intermediates and three (cysteine, tyrosine and hydroxylysine) from nutritionally essential amino acids. Identification of the twelve amino acids that humans can synthesize rested primarily on data derived from feeding diets in which purified amino acids replaced protein. This chapter considers only the biosynthesis of the twelve amino acids that are synthesized in human tissues, not the other eight that are synthesized by plants. 

Bizzarri R, Serresi M, Cardarelli F, Abbruzzetti S, Campanini B, Viappiani C, Beltram F (2009) Single amino acid replacement makes Aequorea victoria fluorescent proteins reversibly photoswitchable. J Am Chem Soc 132 85-95... 

A base substitution can also result in the formation of a new inappropriate terminator (or non-sense) codon, and are thus known as non-sense mutations. The polypeptide formed from such mutated genes will be shorter than normal and is most likely to be inactive. Owing to the redundancy of the genetic code, about a quarter of all possible base substitutions will not result in an amino acid replacement and will be silent mutations. 

Electrophoresis as a method of study of molecular differences has its limitations. It can demonstrate variation of the primary structure only if it changes migration in the electric field, which is the case only for a fraction (about one third) of the conceivable variants the others are electrophoretically silent. On the other hand, different amino acid replacements may cause the same electrophoretic variant and thus be indistinguishable. Furthermore, the whole method was applicable only to selected types of proteins and could not yield a genetically satisfactory overview. 

Third, the genes for both proteins have been successfully cloned [24], This cloning provides an approach to test the role of specific residue interactions in binding, by synthesizing proteins with single amino acid replacements. We consider each of these points in the following sections. 

Massanz, C. and Friedrich, B. (1999) Amino acid replacements at the H(2)-activating site of the NAD-reducing hydrogenase from Alcaligenes eutrophus. Biochemistry, 38, 14330-7. 

Amino Acid Replacements for Allosteric Control in Crocodilian Hemoglobins ... 

Some amino acid replacements are conservative some are not... 

A nonconservative amino acid replacement underlies sickle cell anemia... 

Amino acid replacements in proteins may be conservative that is, an amino acid of one class is replaced by another of the same class, e.g., alanine is replaced by valine. Conservative replacements frequently have little impact on protein structure or function. 

Compare this situation with that for normal and sickle cell hemoglobins. The two COX enzymes are both fully functional and differ by a single conservative amino acid replacement. In contrast, normal hemoglobin is fully functional but sickle cell hemoglobin is not and these differ by a single nonconservative amino acid replacement (see chapter 11). 

Homocysteine, which initiates proatherogenic changes in endothelium, can be reduced in many patients by restriction of total protein intake to the amount required for amino acid replacement. Supplementation with folic acid plus other vitamins is indicated in severe homocyteinemia. 

Suzuki, T. Sugimura, N. Taniguchi, T. Unemi, Y. Murata, T. Hayashida, M. Yokouchi, K. Uda, K. Furukohri, T. Two-domain arginine kinases from the clams Solen strictus and Corbicula japonica exceptional amino acid replacement of the functionally important D62 by G. Int. J. Biochem. Gell Biol., 34, 1221-1229 (2002)... 

How can one mutation be suppressed by a second mutation at a different point in the chromosome Rarely, a mutation is suppressed by a second mutation within the same gene. Such intragenic complementation sometimes occurs when a mutation leads to an amino acid replacement that disrupts the structural stability or function of a protein. Sometimes a mutation at another site involving a residue, which interacts with the first amino acid replaced, will alter the inter-... 

A single-base mutation resulting in an amino-acid change that may not alter the biological activity of the protein because the amino-acid replacement is in a noncriticai position and also resembles the normal amino-acid also a silent mutation... 

A hypothetical beneficial mutation, in which the amino-acid replacement yields a protein with improved biological activity, giving the mutated organism an advantage it is not possible to predict advantageous amino-acid replacements... 

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