Evidence for fatty acid oxidation in human placenta, and the relationship of fatty acid oxidation enzyme activities with gestational age.
Fetal disorders of mitochondrial fatty acid oxidation have recently been associated with obstetric complications including pre-eclampsia, Hemolysis, Elevated Liver enzymes, Low Platelets (HELLP) syndrome, placental floor infarct, and Acute Fatty Liver of Pregnancy (AFLP). These diseases occur in about a third of the mothers who are heterozygous for a defect in long chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) enzyme and who bear a fetus homozygous for the defect. The mechanism of this association is not clearly understood. In this study, we provide evidence that the placenta may be the site of production of toxic intermediates of fatty acid metabolism, which accumulate to cause liver damage in the mother. We show that two critical enzymes of long chain fatty acid metabolism, long chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) and short chain 3-hydroxyacyl-CoA dehydrogenase (SCHAD), are active in the normal human placenta. There is an inverse correlation between the enzyme activity of both the enzymes and maternal gestational age during the second and third trimesters. We believe that the demonstration of fatty acid oxidation enzyme activity by the placenta is the first step towards assessing a possible role for fetal/placental fatty acid oxidation defects in the pathogenesis of a subset of pregnancy complications.
Rakheja
D
D
Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Bennett
M J
MJ
Foster
B M
BM
Domiati-Saad
R
R
Rogers
B B
BB
D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000145:classification / Q000378:metabolism; D000328:Adult; D002824:Chorionic Villi / Q000201:enzymology*; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D005865:Gestational Age; D006801:Humans; D010084:Oxidation-Reduction; D011247:Pregnancy / Q000378:metabolism*; D011248:Pregnancy Complications / Q000201:enzymology / Q000209:etiology
D005227:Fatty Acids; D015094:3-Hydroxyacyl CoA Dehydrogenases