Leaky beta-oxidation of a trans-fatty acid: incomplete beta-oxidation of elaidic acid is due to the accumulation of 5-trans-tetradecenoyl-CoA and its hydrolysis and conversion to 5-trans-tetradecenoylcarnitine in the matrix of rat mitochondria.
The degradation of elaidic acid (9-trans-octadecenoic acid), oleic acid, and stearic acid by rat mitochondria was studied to determine whether the presence of a trans double bond in place of a cis double bond or no double bond affects beta-oxidation. Rat mitochondria from liver or heart effectively degraded the coenzyme A derivatives of all three fatty acids. However, with elaidoyl-CoA as a substrate, a major metabolite accumulated in the mitochondrial matrix. This metabolite was isolated and identified as 5-trans-tetradecenoyl-CoA. In contrast, little or none of the corresponding metabolites were detected with oleoyl-CoA or stearoyl-CoA as substrates. A kinetic study of long-chain acyl-CoA dehydrogenase (LCAD) and very long-chain acyl-CoA dehydrogenase revealed that 5-trans-tetradecenoyl-CoA is a poorer substrate of LCAD than is 5-cis-tetradecenoyl-CoA, while both unsaturated acyl-CoAs are poor substrates of very long-chain acyl-CoA dehydrogenase when compared with myristoyl-CoA. Tetradecenoic acid and tetradecenoylcarnitine were detected by gas chromatography/mass spectrometry and tandem mass spectrometry, respectively, when rat liver mitochondria were incubated with elaidoyl-CoA but not when oleoyl-CoA was the substrate. These observations support the conclusion that 5-trans-tetradecenoyl-CoA accumulates in the mitochondrial matrix, because it is less efficiently dehydrogenated by LCAD than is its cis isomer and that the accumulation of this beta-oxidation intermediate facilitates its hydrolysis and conversion to 5-trans-tetradecenoylcarnitine thereby permitting a partially degraded fatty acid to escape from mitochondria. Analysis of this compromised but functional process provides insight into the operation of beta-oxidation in intact mitochondria.
Department of Chemistry, City College and Graduate Center of the City University of New York, New York, New York 10031, USA.
Wenfeng
W
Yu
Xiquan
X
Liang
Regina E
RE
Ensenauer
Jerry
J
Vockley
Lawrence
L
Sweetman
Horst
H
Schulz
D000818:Animals; D005231:Fatty Acids, Unsaturated / Q000737:chemistry / Q000378:metabolism; D006868:Hydrolysis; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008930:Mitochondria, Liver / Q000378:metabolism; D019301:Oleic Acid / Q000737:chemistry* / Q000378:metabolism*; D009829:Oleic Acids; D010084:Oxidation-Reduction; D010101:Oxygen Consumption; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism
D005231:Fatty Acids, Unsaturated; D009829:Oleic Acids; D019301:Oleic Acid; C011459:elaidic acid