Structure-activity relationship of the effect of cis-unsaturated fatty acids on heart sarcolemmal phospholipase D activity.
This study examined the role of fatty acids on the phosphatidylcholine-specific phospholipase D (PLD) function of purified sarcolemmal (SL) membranes isolated from rat hearts. The enzyme's hydrolytic activity was determined by measuring [14C] phosphatidic acid formation from exogenous [14C] phosphatidylcholine (PtdCho) in the absence or presence of the sodium salts of various saturated or unsaturated long-chain fatty acids (FA). In certain experiments the enzyme was also assayed in the transphosphatidylation mode. Cis-unsaturation and free carboxyl groups were structural prerequisites for the stimulatory effect exerted by FA on SL PLD. The most effective compounds were arachidonate and oleate, which maximally activated PLD at 4 and 5 mM concentration, respectively. To verify if a detergent-like mechanism was involved in PLD activation, anionic, zwitterionic and non-ionic detergents were used. Only anionic taurodeoxycholate had a slight effect, which was about 7% of that achieved by arachidonate or oleate. These results suggest that cis-unsaturated FA activate cardiac sarcolemmal PLD by a mechanism(s) which seems to be unrelated to non-specific perturbation of the membrane.
Dai
J
J
Division of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, Canada.
Williams
S A
SA
Ziegelhöffer
A
A
Panagia
V
V
D000818:Animals; D005227:Fatty Acids / Q000737:chemistry / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D008297:Male; D009206:Myocardium / Q000201:enzymology*; D010713:Phosphatidylcholines / Q000378:metabolism; D010739:Phospholipase D / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012508:Sarcolemma / Q000201:enzymology*; D013268:Stimulation, Chemical; D013329:Structure-Activity Relationship; D013501:Surface-Active Agents / Q000494:pharmacology*
D005227:Fatty Acids; D005231:Fatty Acids, Unsaturated; D010713:Phosphatidylcholines; D013501:Surface-Active Agents; D010739:Phospholipase D