Hydroxylation of lauramide diethanolamine by liver microsomes.
Lauramide diethanolamine (LDEA)--a compound used in cosmetics and soap products as an emollient, thickener, and foam stabilizer--was observed to be metabolized by rat liver microsomes to two major products that were identified by GC/MS to be the 11-hydroxy and 12-hydroxy derivatives of LDEA. The specific activities for LDEA 11- and 12-hydroxylation in microsomes prepared from control rats were 2.23 +/- 0.40 and 0.71 +/- 0.17 nmol/min/mg protein, respectively. Treatment of rats with the cytochrome P4504A inducer and peroxisome proliferator, diethylhexyl phthalate, increased the LDEA 12-hydroxylation rate to 3.50 +/- 0.48 nmol/min/mg protein, a 5-fold increase in specific activity, whereas the LDEA 11-hydroxylase activity remained unchanged. Because LDEA contains a 12-carbon side chain, LDEA hydroxylation rates were compared with the hydroxylation rates for lauric acid. The specific activities of lauric acid 11- and 12-hydroxylation reactions in diethylhexyl phthalate-treated rats were 1.7-fold and 3.2-fold greater than the LDEA 11- and 12-hydroxylation rates, respectively. When LDEA hydroxylation reactions were performed in the presence of a polyclonal antibody to the rat P4504A forms, formation of 12-hydroxy-LDEA was inhibited by 80%. Rat kidney microsomes also supported the hydroxylation of LDEA at its 11- and 12-carbon atoms, with specific activities of 0.05 +/- 0.01 and 0.28 +/- 0.02 nmol/min/mg protein, respectively. LDEA was also metabolized to 11- and 12-hydroxy derivatives by human liver microsomes at specific activities of 0.22 +/- 0.06 and 0.84 +/- 0.26 nmol/min/mg protein, respectively.
Merdink
J
J
Department of Pharmaceutical Sciences, Washington State University, Pullman 99164-6510, USA.
Decosta
K
K
Mathews
J M
JM
Jones
C B
CB
Okita
J R
JR
Okita
R T
RT
D000818:Animals; D042926:Cytochrome P-450 CYP4A; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D004643:Emollients / Q000378:metabolism*; D004790:Enzyme Induction; D004983:Ethanolamines / Q000378:metabolism*; D006801:Humans; D006900:Hydroxylation; D007668:Kidney / Q000378:metabolism* / Q000648:ultrastructure; D007850:Lauric Acids / Q000378:metabolism*; D008297:Male; D008861:Microsomes / Q000378:metabolism*; D008862:Microsomes, Liver / Q000378:metabolism*; D006899:Mixed Function Oxygenases / Q000096:biosynthesis; D015394:Molecular Structure; D051381:Rats; D017207:Rats, Sprague-Dawley
D004643:Emollients; D004983:Ethanolamines; D007850:Lauric Acids; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D042926:Cytochrome P-450 CYP4A; C052237:lauric acid diethanolamide