Effects of CoA and acyl-CoA on Ca(2+)-permeability of endoplasmic-reticulum membranes from rat liver.
We have studied the effects of CoA and palmitoyl-CoA on Ca2+ movements and GTP-dependent vesicle fusion in rat liver microsomes. (1) Inhibition of membrane fusion by CoA depends on esterification of CoA to long-chain acyl-CoA using endogenous non-esterified fatty acids. (2) Binding of long-chain acyl-CoA to microsomal membranes is inhibited by BSA, which also relieves inhibition of membrane fusion. (3) Under conditions where acyl-CoA binding is inhibited, CoA causes increased Ca2+ accumulation, apparently by decreasing the Ca2+ leak rate. (4) Conversely, palmitoyl-CoA, in the presence of BSA, causes Ca2+ efflux. (5) The decrease in Ca(2+)-permeability caused by CoA does not depend on the presence of ATP or GTP, and is irreversible in the short term. (6) Using 14C-labelled CoA we show that CoA derivatives can be formed from endogenous components of microsomal membranes in the absence of ATP. (7) The results are interpreted in terms of a Ca(2+)-permeability which is controlled by CoA and/or long-chain acyl-CoA esters.
Rich
G T
GT
School of Biological Sciences, University of East Anglia, Norwich, U.K.
Comerford
J G
JG
Graham
S
S
Dawson
A P
AP
D000214:Acyl Coenzyme A / Q000494:pharmacology*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D003065:Coenzyme A / Q000494:pharmacology*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D051381:Rats
D000214:Acyl Coenzyme A; D003065:Coenzyme A; D002118:Calcium