Inhibition of Synthesis of Fetal Hemoglobin by an Isoleucine Analogue

George R. Honig

doi:10.1172/JCI105668

Department of Pediatrics, University of Illinois College of Medicine, Chicago, Illinois

‡

U. S. Public Health Service Graduate Trainee in Pediatric Hematology (5 TO1 AM 05344), National Institute of Arthritis and Metabolic Diseases, University of Illinois College of Medicine.

Address requests for reprints to Dr. George R. Honig, Department of Pediatrics, University of Illinois College of Medicine, 840 S. Wood Street, Chicago, Ill. 60612.

Received for publication 19 May 1967 and in revised form 14 July 1967.

Supported by a graduate training grant (5 TO1 AM 05344) from the National Institute of Arthritis and Metabolic Diseases, and a grant (RG HD 00568) from the National Institute of Child Health and Human Development, National Institutes of Health, U. S. Public Health Service.

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Published November 1, 1967 - More info

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Abstract

Reticulocytes from newborn infants with Rh isoimmune hemolytic disease actively incorporated radioactive amino acids in vitro into hemoglobins F and A. Approximately 50% of the reticulocytes appeared capable of synthesis of both of these hemoglobins within the same cell, as demonstrated by the selective elution technique of Betke and Kleihauer. An isoleucine analogue, L-O-methylthreonine, inhibited the incorporation of a variety of amino acids into hemoglobin F, without significantly affecting the synthesis of hemoglobin A. The inhibition was prevented upon concomitant addition of L-isoleucine to the medium. These observations suggest that an independent biosynthetic apparatus is present in the cell for the synthesis of each of these two hemoglobins. Because isoleucine is present only in the gamma chains of hemoglobin F, the inhibitory effect of the analogue on the synthesis of this hemoglobin must represent a selective effect on the production of gamma chains.