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