Characteristics of the inhibition of hemoglobin synthesis in rabbit reticulocytes by threo-α-amino-β-chlorobutyric acid

Abstract

• 1.

  1. Addition of the valine antagonist, α-amino-β-chlorobutyric acid, to rabbit reticulocytes produces a rapid inhibition of hemoglobin synthesis with a subsequent increase in labelling of protein of the ribosomal fraction.

• 2.

  2. At appropriate antagonist: valine ratios, the incorporation of valine itself occurs at the ribosomal level, but is inhibited in hemoglobin. This indicates that the block in hemoglobin synthesis is caused by substitution of the analogue for valine at specific valine sites, and it is suggested that the loci of these substitutions may be the Val-Val residues on the precursor protein of the β-chain.

• 3.

  3. The antagonist also inhibits [¹⁴C]isoleucine incorporation into hemoglobin, but unlike other amino acids, isoleucine does not accumulate in protein of the ribosomal fraction. This observation is discussed in relation to the characteristics of isoleucine incorporation into reticulocyte proteins and the location of residues of this amino acid near the NH₂-terminal end of the α-chain of rabbit hemoglobin.

• 4.

  4. Synthesis of both the α- and β-chains of hemoglobin is blocked by the antagonist and there is no evidence for the preferential synthesis and release of either chain.

• 5.

  5. Abortive protein formed in the presence of the antagonist is rapidly degraded into trichloroaceeric acid-soluble products.