Phosphatidylcholine biosynthesis in myocardial ischaemia.
In this study the effect of myocardial ischaemia was evaluated on two aspects of phospholipid metabolism: (i) the de novo synthesis of myocardial phospholipids, as indicated by the incorporation of (methyl-3H) choline and (ii) the incorporation of radiolabelled long chain fatty acids into tissue phospholipids. Two models of ischaemia were used namely normothermic ischaemic arrest and hypoxic, low-flow perfusion of the isolated rat heart. The results showed that within 10 min, hypoxic low-flow perfusion significantly inhibited the incorporation rate of (methyl-3H) choline into tissue phospholipids. Since the tissue choline content remained unaltered under these conditions, the results suggested that the de novo synthesis of phosphatidylcholine is very susceptible to ischaemic damage. Inhibition of (methyl-3H) choline incorporation into tissue phospholipids appeared to be due to both a reduction in choline uptake and specific inhibition of the CDP pathway. Perfusion with glucose (10 mM) as substrate completely abolished the ischaemia-induced reduction in (methyl-3H) choline incorporation, indicating that glycolytically produced ATP played an important role in phosphatidylcholine biosynthesis. In contrast to these results, myocardial ischaemia stimulated the incorporation of long-chain saturated and unsaturated fatty acids into tissue phospholipids. In summary, the results obtained showed that myocardial ischaemia profoundly affected phospholipid metabolism which, in turn, might contribute to membrane damage.
Lochner
A
A
Department of Medical Physiology and Biochemistry, University of Stellenbosch Medical School, Tygerberg, Republic of South Africa.
de Villiers
M
M
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002794:Choline / Q000378:metabolism; D002797:Choline Kinase / Q000378:metabolism; D019916:Choline-Phosphate Cytidylyltransferase; D003327:Coronary Disease / Q000378:metabolism*; D003570:Cytidine Triphosphate / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism; D009713:Nucleotidyltransferases / Q000378:metabolism; D010713:Phosphatidylcholines / Q000096:biosynthesis*; D010743:Phospholipids / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains
D005227:Fatty Acids; D010713:Phosphatidylcholines; D010743:Phospholipids; D003570:Cytidine Triphosphate; D000255:Adenosine Triphosphate; D002797:Choline Kinase; D009713:Nucleotidyltransferases; D019916:Choline-Phosphate Cytidylyltransferase; D002794:Choline