Journal of Lipid Research, Vol 35, 698-708, Copyright © 1994 by Lipid Research, Inc.
Mitochondrial metabolism of 12- and 15-hydroxyeicosatetraenoic acids
JA Gordon, KM Broekemeier, AA Spector and DR Pfeiffer
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242.
We have previously demonstrated that peroxisomal-deficient human skin
fibroblasts and mutant Chinese hamster ovary cells do not convert 12- and
15-hydroxyeicosatetraenoic acids (HETEs) to chain-shortened, polar
metabolites, suggesting that peroxisomes are the intracellular location for
beta-oxidation of these compounds. This implies that mitochondria do not
beta-oxidize HETEs. To test this hypothesis we incubated highly purified
rat liver mitochondria with [3H]12-(S)- and [3H]15-(S)-HETE in the presence
of carnitine and an acylcoenzyme A-generating system. Extracts obtained
from these incubations were analyzed for radiolabeled polar metabolites.
Both HETEs were converted to apparent products of beta-oxidation, although
the 12-HETE compound was a markedly better substrate. The presence of 50
microM 2-tetradecyloxirane carboxylate, a potent inhibitor of carnitine
palmitoyl transferase, completely blocked 12- and 15-HETE conversion to
these metabolites as did omission of carnitine from the medium. These data
demonstrate carnitine-dependent beta-oxidation of HETEs in isolated
mitochondria and suggest that mitochondria are competent to carry out this
metabolic process in eukaryotic cells. Prevailing metabolic conditions in
subcellular compartments may have precluded observation of mitochondrial
activity in our earlier work with cultured cells. Alternatively, transport
mechanisms may exist in the cell types studied that distribute 12-(S)- and
15-(S)-HETEs specifically to peroxisomes.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
