Ferriheme and ferroheme are isosteric inhibitors of fatty acid binding to rat liver fatty acid binding protein.
In addition to fatty acids, liver fatty acid binding protein (L-FABP) also interacts with ferriheme, which it binds with an affinity approximately one order of magnitude greater than that for oleic acid. We have, therefore, examined the effect of ferroheme and ferriheme on the binding of oleate to rat L-FABP also called heme-binding protein. Both oxidation states of heme behaved as isosteric inhibitors for the binding of the fatty acid confirming a common binding site. The reduced form of heme (Fe(II)) is a threefold better competitor of oleate binding than ferriheme. To show whether the diffusion of heme would be affected by the presence of the binding protein, we measured the effect of the fatty acid binding protein on the diffusional flux of a water-soluble heme derivative, iron-deuteroporphyrin. The diffusional flux of iron-deuteroporphyrin did not change in the presence of the protein. This suggested that the binding affinity of fatty acid binding protein for iron-deuteroporphyrin is too great to allow rapid equilibrium between bound and unbound ligand across the system in an appropriate time frame.
Stewart
J M
JM
Mount Allison University, Sackville, Canada.
Slysz
G W
GW
Pritting
M A
MA
Muller-Eberhard
U
U
D000818:Animals; D002352:Carrier Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004058:Diffusion; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D006418:Heme / Q000737:chemistry / Q000494:pharmacology*; D007501:Iron / Q000737:chemistry; D008099:Liver / Q000378:metabolism; D018996:Myelin P2 Protein / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D019301:Oleic Acid / Q000378:metabolism; D010084:Oxidation-Reduction; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D002352:Carrier Proteins; C493320:Fabp1 protein, mouse; C493321:Fabp1 protein, rat; C490174:Fabp7 protein, rat; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids; D018996:Myelin P2 Protein; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D019301:Oleic Acid; D006418:Heme; D007501:Iron