title: Potential role of middle molecular compounds in the development of uremic anemia.
abstract: In preceding papers it was demonstrated that middle molecular fractions isolated from uremic patients (MM) impair hemoglobin synthesis by inhibiting the enzyme Delta-aminolevulinic acid dehydrase (D-ALA-D) and by diminishing the globin synthesis in reticulocytes from healthy subjects. Additionally, the susceptibility to oxidative damage of erythrocytes is increased in the presence of MM. Studies were undertaken to elucidate the underlying mechanisms. It was found that the MM induced D-ALA-D inhibition is reversed both by Zn and by GSH in vitro indicating that MM exert their effect on the enzyme either by affecting essential SH-groups within the enzyme molecule or by altering the enzyme configuration by interaction with the Zn atom. MM causing an increased oxidative hemolysis rate (OHR) also inhibit the catalase activity and the glucose consumption of normal and uremic erythrocytes. It is concluded that the augmented OHR in uremia is induced by accumulating hydrogen peroxide which cannot be sufficiently removed due to the MM mediated catalase inhibition and the concomitant impairment of the glucose utilisation.
mesh_terms: D000740:Anemia / Q000209:etiology* / Q000503:physiopathology; D004912:Erythrocytes / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D006435:Renal Dialysis; D014118:Toxins, Biological / Q000302:isolation & purification / Q000494:pharmacology / Q000502:physiology*; D014511:Uremia / Q000150:complications* / Q000503:physiopathology
chemical_list: D014118:Toxins, Biological; C026865:uremia middle molecule toxins