Estrogen esters as substrates for human paraoxonases.
Mammalian paraoxonases (PONs 1, 2 and 3) are a highly conserved family of esterases, with uncertain physiological functions and natural substrates. Here we characterize the ability of purified recombinant human PONs to hydrolyze estrogen esters, a class of compounds previously not known to be PON substrates. PONs hydrolyzed estrogen mono- and diesters at position 3 of the steroid A-ring. Diesters were better substrates for the PONs and were very efficiently hydrolyzed, particularly by PON3. Esters at position 17 were not cleaved by the PONs unless an adjacent double bound was present. Purified human serum butyryl cholinesterase also hydrolyzed estrogen esters, however it preferably hydrolyzed the mono-esters. The ability of the PONs' to effectively hydrolyze a variety of estrogen esters provides further insight into the structure of their active sites and suggests that natural compounds with aromatic ester groups might be relevant substrates for the PONs.
Teiber
John F
JF
Department of Internal Medicine, Division of Epidemiology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Billecke
Scott S
SS
La Du
Bert N
BN
Draganov
Dragomir I
DI
D000818:Animals; D043303:Aryldialkylphosphatase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D002460:Cell Line; D004950:Esterases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004952:Esters; D004967:Estrogens / Q000737:chemistry* / Q000378:metabolism; D004970:Estrone / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D009036:Moths / Q000235:genetics; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D013379:Substrate Specificity
D004952:Esters; D004967:Estrogens; D011994:Recombinant Proteins; D004970:Estrone; D004950:Esterases; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human; C468411:PON2 protein, human; C113656:PON3 protein, human