Hemoglobin as a source of endogenous bioactive peptides: the concept of tissue-specific peptide pool.
Scattered literature data on biologically active hemoglobin-derived peptides are collected in the form of tables. Respective structure-functional 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. At that stage alpha- and beta-globin chains of hemoglobin predominantly give rise to relatively long peptides containing ca. 30 amino acid residues. The primary proteolysis is followed by the next degradation step coupled with excretion of newly formed shorter peptides form red blood cells. Both the primary and the secondary proteolysis products are subjected to further stepwise C- and N-terminal chain shortening, giving rise to families of closely related peptides that are actually found in animal tissue extracts. The possible sites of primary proteolysis are compared with the positions of the exposed secondary structure elements within the monomeric alpha- and beta-globins as well as the tetrameric hemoglobin. Two tentative schemes are proposed for hemoglobin degradation, one of which starts at the globin loops exposed on the surface of the tetramer and the other, at monomeric globins where more sites are available for the action of proteases. 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 that description, hemoglobin is only a single example, although an important one, of a vast number of functional proteins providing their proteolytically derived fragments for maintaining the tissue homeostasis.
Ivanov
V T
VT
Shemyakin-Ovchinnikov, Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.
Karelin
A A
AA
Philippova
M M
MM
Nazimov
I V
IV
Pletnev
V Z
VZ
D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D015415:Biomarkers; D001921:Brain / Q000378:metabolism / Q000473:pathology; D004912:Erythrocytes / Q000737:chemistry; D005260:Female; D006454:Hemoglobins / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008297:Male; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D017433:Protein Structure, Secondary
D015415:Biomarkers; D006454:Hemoglobins; D010446:Peptide Fragments