Coenzyme A-dependent cleavage of membrane phospholipids in several rat tissues: ATP-independent acyl-CoA synthesis and the generation of lysophospholipids.
Substantial amounts of acyl-CoA were formed when microsomes from several rat tissues were incubated with varying concentrations of free CoA and bovine serum albumin even in the absence of ATP and Mg2+. For instance, 86 nmol of acyl-CoA was produced when microsomes (5 mg protein) were incubated with 300 microM CoA for 30 min. It was calculated that 1.8% of total fatty acyl residues were converted to acyl-CoA during the incubation. No appreciable amount of acyl-CoA was formed from free fatty acid or from boiled microsomes under the same experimental conditions. These observations indicate that acyl-CoA is formed from microsomal lipids by an enzyme activity distinct from previously known long-chain fatty acyl-CoA synthetase. The apparent Km value for CoA and Vmax were 180 microM and 20 nmol/30 min per mg protein, respectively. We found that several species of acyl-CoA such as arachidonoyl-CoA were preferentially synthesized through the reaction and that several types of phospholipids actually act as acyl donors in the formation of acyl-CoA. Phosphatidylinositol and phosphatidylcholine appear to be preferred substrates. We confirmed that lysophosphatidylinositol and lysophosphatidylcholine were generated along with the formation of acyl-CoA. It seems very likely that CoA-mediated cleavage of phospholipids/ATP-independent acyl-CoA synthesis is implicated in the metabolism of certain types of fatty acyl residues of membranous phospholipids in mammalian cells.
Sugiura
T
T
Faculty of Pharmaceutical Sciences, Teikyo University, Kanagawa, Japan.
Kudo
N
N
Ojima
T
T
Mabuchi-Itoh
K
K
Yamashita
A
A
Waku
K
K
D000214:Acyl Coenzyme A / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001081:Apyrase / Q000494:pharmacology; D003065:Coenzyme A / Q000378:metabolism*; D008246:Lysophospholipids / Q000378:metabolism*; D008297:Male; D008563:Membrane Lipids / Q000378:metabolism*; D008861:Microsomes / Q000378:metabolism; D008862:Microsomes, Liver / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
D000214:Acyl Coenzyme A; D008246:Lysophospholipids; D008563:Membrane Lipids; D010743:Phospholipids; D000255:Adenosine Triphosphate; D001081:Apyrase; D003065:Coenzyme A