On the rate-limiting step in the beta-oxidation of polyunsaturated fatty acids in the heart.
This study was conducted to determine if the activity of 2,4-dienoyl-CoA reductase limits the rate of cardiac beta-oxidation of highly unsaturated fatty acids. Although growth hormone treatment of hypophysectomized rats caused a 3-fold increase in the activity of 2,4-dienoyl-CoA reductase, beta-oxidation of docosahexaenoate in cardiomyocytes was not stimulated by this treatment. Since cardiomyocytes oxidized oleic acid more rapidly than docosahexaenoic acid, the utilization of energy did not limit beta-oxidation. Respiration measurements with coupled rat heart mitochondria revealed that the rates of beta-oxidation with palmitoyl-CoA and palmitoylcarnitine as substrates were virtually identical but were 3- to 4-fold higher than the rates obtained with either docosahexaenoyl-CoA or docosahexaenoylcarnitine. Although the activity of carnitine palmitoyltransferase I (CPT I) was 5 times higher with palmitoyl-CoA as substrate than with docosahexaenoyl-CoA, this reaction is only one of several that may limit the beta-oxidation of docosahexaenoic acid. Surprisingly, an incremental inhibition of CPT I resulted in a parallel inhibition of respiration supported by either palmitoyl-CoA or docosahexaenoyl-CoA. This observation agrees with the notion that CPT I may also be a regulatory enzyme in cardiac fatty acid oxidation. It is concluded that the reduction of double bonds by 2,4-dienoyl-CoA reductase does not restrict the cardiac beta-oxidation of highly unsaturated fatty acid, like docosahexaenoic acid.
Nada
M A
MA
Department of Chemistry, City College of the City University of New York, NY 10031, USA.
Abdel-Aleem
S
S
Schulz
H
H
D000818:Animals; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism; D004281:Docosahexaenoic Acids / Q000378:metabolism; D044943:Fatty Acid Desaturases / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D013006:Growth Hormone / Q000494:pharmacology; D008297:Male; D008929:Mitochondria, Heart / Q000378:metabolism; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D019301:Oleic Acid; D009829:Oleic Acids / Q000378:metabolism; D044925:Oxidoreductases Acting on CH-CH Group Donors; D051381:Rats; D017207:Rats, Sprague-Dawley
D005231:Fatty Acids, Unsaturated; D009829:Oleic Acids; D004281:Docosahexaenoic Acids; D019301:Oleic Acid; D013006:Growth Hormone; D044943:Fatty Acid Desaturases; D044925:Oxidoreductases Acting on CH-CH Group Donors; C100153:2,4-dienoyl-CoA reductase; D002334:Carnitine O-Palmitoyltransferase