Interaction between the synthesis of alpha and beta globin.
We have examined the relationship between alpha and beta globin chain syntheses by utilizing the distribution of isoleucyl residues in rabbit hemoglobin. The alpha globin chain contains three isoleucyl residues while the beta chain of certain rabbits contains no isoleucine. O-Methyl-L-threonine, an isoleucine isostere, inhibits incorporation of radiolabeled amino acids into alpha chains in rabbit reticulocytes. When alpha chain synthesis is inhibited by 50-85%, beta synthesis is stimulated by 15-50%. The excess labeled beta chains are not distinguishable from authentic beta chains by any of the following criteria: (a) carboxymethyl cellulose chromatography in sodium phosphate-urea buffers, (b) electrophoresis on polyacrylamide gels containing sodium dodecyl sulfate, and (c) electrophoresis of methionine-containing tryptic peptides. The stimulation of beta synthesis continues after the pool of excess alpha chains has been exhausted by preincubation with O-methyl-L-threonine. The stimulation does not occur, however, when 1 mM 2-mercaptoethanol is added to the incubation medium or when the cells are excessively diluted in the incubation mixture. The rates of beta chain initiation and elongation during stimulation have been compared to the rates during normal synthesis. Although both rates are increased, the rate of elongation increases more than initiation, suggesting that initiation is the rate-limiting step in increased beta chain production. The stimulation of beta synthesis when alpha synthesis is inhibited is interpreted as resulting from relief of competition between alpha and beta mRNAs for limiting components of the protein synthetic apparatus.
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D005914:Globins / Q000096:biosynthesis*; D006579:Heterozygote; D006720:Homozygote; D007532:Isoleucine / Q000378:metabolism; D008239:Lysine / Q000378:metabolism; D008623:Mercaptoethanol / Q000494:pharmacology; D008715:Methionine / Q000378:metabolism; D010441:Peptide Chain Elongation, Translational / Q000187:drug effects; D010442:Peptide Chain Initiation, Translational / Q000187:drug effects; D010446:Peptide Fragments / Q000096:biosynthesis; D011132:Polyribosomes / Q000378:metabolism; D011817:Rabbits; D012156:Reticulocytes / Q000378:metabolism; D013912:Threonine / Q000031:analogs & derivatives / Q000494:pharmacology
D000596:Amino Acids; D010446:Peptide Fragments; D007532:Isoleucine; D013912:Threonine; D008623:Mercaptoethanol; D005914:Globins; D008715:Methionine; D008239:Lysine