Russian Journal of Bioorganic Chemistry, Vol. 24, No. 4, 1998 p. 241

Proteolytic Degradation of Hemoglobin in Erythrocytes Yields
Biologically Active Peptides

A. A. Karelin1, M. M. Filippova, O. N. Yatskin, E. Yu. Blishchenko,
I. V. Nazimov, and V. T. Ivanov

Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences,
ul. Miklukho-Maklaya 16/10, Moscow, 117871 Russia

Received September 4, 1997; in final form, December 10, 1997

Abstract: The formation of biologically active hemoglobin fragments in human erythrocytes was studied. The
structures of 33 peptide products of intraerythrocytic hemoglobin cleavage were determined. Based on an anal-
ysis of these sequences, a model of the stepwise degradation of the hemoglobin α- and β-chains was suggested.
The processes of peptide formation in a cell-free erythrocyte lysate system were studied. The involvement of
an enzymatic complex of the cell membrane fraction was demonstrated. It was found that the cells of a surviving
human erythrocyte culture secrete short (of 5–20 amino acid residues) peptides, and the structures of 36 pep-
tides were determined. The dynamics of peptide secretion was investigated, and preliminary data on the energy-
dependence of this process were obtained. Based on the experimental results, a model describing erythrocytes
as an endocrine gland was suggested.

Key words: hemoglobin, proteolytic enzymes, erythrocyte surviving culture, secretion