Induced hemichrome formation of methemoglobins A, S and F by fatty acids, alkyl ureas and urea.
1. Spectral analysis of the Soret region (450-350 nm) has shown that saturated fatty acids, alkyl ureas and urea induce the conversion of methemoglobins A, S, and F to the hemichrome state. 2. In the presence of fatty acids (C8-C16), methemoglobin F is converted to the hemichrome state more readily than either methemoglobins A or S. 3. Using several alkyl ureas (methyl, ethyl, propyl, butyl), the extent of hemichrome formation was as follows: met Hb F > met Hb S > met Hb A. The ability of these compounds to induce hemichrome formation is related to their increasing hydrophobicity. 4. Conversion to the hemichrome state in the presence of urea (5M) led to the formation of molecular aggregates of hemoglobins S, F and A which may be initiated by subunit dissociation and conformational changes, coupled to increased globin-globin interactions. 5. Similar aggregation occurred for methemoglobin S in the presence of octanoic acid; no significant aggregation was evident for methemoglobin A after 10 hr of exposure to octanoic acid.
Harrington
J P
JP
Department of Chemistry and Comprehensive Sickle Cell Center, University of South Alabama, Mobile 36688.
Newton
P
P
Crumpton
T
T
Keaton
L
L
D002850:Chromatography, Gel; D004912:Erythrocytes / Q000187:drug effects; D005227:Fatty Acids / Q000494:pharmacology*; D005319:Fetal Hemoglobin / Q000737:chemistry; D006420:Hemeproteins / Q000737:chemistry*; D006441:Hemoglobin A / Q000737:chemistry; D006451:Hemoglobin, Sickle / Q000737:chemistry; D006801:Humans; D008706:Methemoglobin / Q000737:chemistry* / Q000187:drug effects; D013056:Spectrophotometry, Ultraviolet; D014508:Urea / Q000031:analogs & derivatives / Q000494:pharmacology*
D005227:Fatty Acids; D006420:Hemeproteins; D006451:Hemoglobin, Sickle; C001332:hemichrome; D014508:Urea; D008706:Methemoglobin; D006441:Hemoglobin A; D005319:Fetal Hemoglobin