Biosynthetic studies of human fetal hemoglobin

Citation

Rogers, Christopher Bruce (1979) Biosynthetic studies of human fetal hemoglobin. Master's thesis, California Institute of Technology. doi:10.7907/9vhd-4p65. https://resolver.caltech.edu/CaltechTHESIS:04022010-090030827

Abstract

Previous investigators have found unbalanced synthesis of Hb F, with γ chain synthesized from 30% to 68% as efficiently as α chain. In this report, biosynthetic studies of 9 umbilical cord bloods and 6 sickle-cell bloods with elevated levels of Hb F gave an efficiency of 47 ± 3% for γ-chain synthesis relative to α-chain synthesis. Amino acid analysis of the minor zones in chain separation chromatograms showed that two peaks, one eluting before and one after γ chain, contain products of γ-chain mRNA. These peaks, however, are insufficient to explain the discrepancy in γ-chain synthesis. A likely explanation for the reduced γ-chain synthesis is that γ-chain mRNA may have a shorter effective lifetime than α - or β-chain mRNA. There would thus be a progressive imbalance in Hb F synthesis after the blood cell leaves the bone marrow and mRNA synthesis stops. A timed study of a single cord blood, with times ranging from 2.5 minutes to 4 hours, showed that incorporation of radioactivity into acetylated γ chain begins at a high value and decreases with respect to unmodified γ chain. This implies that the γ chain may be modified either on the ribosome or shortly after release, but in any case earlier than 2.5 minutes after the start of incubation.

Thesis Files