LR16, a compound with potent effects on the oxygen affinity of hemoglobin, on blood cholesterol, and on low density lipoprotein.
2-[4-(3,4-Dichlorophenylureido)phenoxy]-2-methylpropionic acid, LR16, combines with two symmetrically related sites in the central cavity of deoxyhemoglobin, 20 A away from the binding site of 2,3-bisphosphoglycerate, and acts as an allosteric effector synergistic with 2,3-bisphosphoglycerate. LR16 (1 mM) raises P50, the partial pressure of oxygen needed to achieve half-saturation with oxygen of a hemolysate of human hemoglobin, about 50 times more strongly than 1 mM 2,3-bisphosphoglycerate. Oral administration of LR16 (at small doses that produced no ill effects) to rats that were fed a diet rich in cholesterol caused substantial reductions of total serum cholesterol and low density lipoprotein-cholesterol, while high density lipoprotein-cholesterol remained unchanged.
Lalezari
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Department of Anesthesiology, Montefiore Medical Center, Bronx, NY.
Rahbar
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Lalezari
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Fermi
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Perutz
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MF
D000818:Animals; D001629:Bezafibrate / Q000494:pharmacology; D002087:Butyrates / Q000494:pharmacology*; D002784:Cholesterol / Q000097:blood*; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D000960:Hypolipidemic Agents / Q000378:metabolism / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000097:blood*; D010100:Oxygen / Q000378:metabolism*; D010671:Phenylurea Compounds / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship
D002087:Butyrates; D006454:Hemoglobins; D000960:Hypolipidemic Agents; D008077:Lipoproteins, LDL; D010671:Phenylurea Compounds; C056904:LR 16; D002784:Cholesterol; D010100:Oxygen; D001629:Bezafibrate