The biosynthesis of human hemoglobin A1c. Slow glycosylation of hemoglobin in vivo.

TLDR

Hemoglobin A1c is produced by nonenzymatic condensation of glucose with the N‑terminal amino groups of β‑chains in Hb A. The authors examined Hb A1c biosynthesis by incubating reticulocytes and bone‑marrow cells with labeled leucine or 59Fe‑transferrin in vitro, and by infusing 59Fe‑transferrin into two subjects to track in vivo formation. Hb A1c accumulates slowly over the 120‑day erythrocyte lifespan, with its specific activity rising gradually to match Hb A by day 60, whereas Hb A peaks within a week; patients with hemolytic anemia show markedly reduced Hb A1c levels.

Abstract

Hemoglobin A1c, the most abundant minor hemoglobin component in human erythrocytes, is formed by the condensation of glucose with the N-terminal amino groups of the beta-chains of Hb A. The biosynthesis of this glycosylated hemoglobin was studied in vitro by incubating suspensions of reticulocytes and bone marrow cells with [3H]leucine or 59Fe-bound transferrin. In all experiments, the specific activity of Hb A1c was significantly lower than that of Hb A, suggesting that the formation of Hb A1c is a posttranslational modification. The formation of Hb A1c in vivo was determined in two individuals who were given an infusion of 59Fe-labeled transferrin. As expected, the specific activity of Hb A rose promptly to a maximum during the 1st week and remained nearly constant thereafter. In contrast, the specific activity of Hb A1c and also of Hbs A1a and A1b rose slowly, reaching that of Hb A by about day 60. These results indicate that Hb A1c is slowly formed during the 120-day life-span of the erythrocyte, probably by a nonenzymatic process. Patients with shortened erythrocyte life-span due to hemolysis had markedly decreased levels of Hb A1c.