HEMOGLOBIN AS A SOURCE OF ENDOGENOUS BIOACTIVE PEPTIDES - THE CONCEPTOF TISSUE-SPECIFIC PEPTIDE POOL

Scattered literature data on biologically active hemoglobin-derived pe ptides are collected in the form of tables. Respective structure-funct ional correlations are analyzed and the general conclusion is reached that hemoglobin fragments must have a profound physiological function. Evidence is presented that generation of hemoglobin fragments starts inside the erythrocytes. Ar that stage alpha- and beta-globin chains o f hemoglobin predominantly give rise to relatively long peptides conta ining ca. 30 amino acid residues. The primary proteolysis is followed by the next degradation step coupled with excretion of newly formed sh orter peptides form red blood cells. Both the primary and the secondar y proteolysis products are subjected to further stepwise C- and N-term inal chain shortening, giving rise to families of closely related pept ides that are actually found in animal tissue extracts. The possible s ires of primary proteolysis are compared with the positions of the exp osed secondary structure elements within the monomeric alpha- and beta -globins as well as the tetrameric hemoglobin. Two tentative schemes a re proposed for hemoglobin degradation, one of which starts at the glo bin loops exposed on the surface of the tetramer and the other, at mon omeric globins where more sites are available for the action of protea ses. The concept of a ''tissue-specific peptide pool'' is formulated, describing a novel system of peptidergic regulation, complementary to the conventional hormonal and neuromodulatory systems. According to th at description, hemoglobin is only a single example, although an impor tant one, of a vast number of functional proteins providing their prot eolytically derived fragments for maintaining the tissue homeostasis. (C) 1997 John Wiley & Sons, Inc.