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Because myocardial ischemia is correlated with both an elevation of intracellular levels of amphiphilic lipid metabolites and a decrease in the rotenone-insensitive NADH cytochrome c reductase (RINCR), we investigated the effects in vitro of some amphiphilic lipid metabolites and synthetic detergents on the activity of RINCR-enriched subfractions of microsomes from isolated cardiac myocytes. RINCR activity was unaffected in vitro by the addition of lysophosphatidylethanolamine (up to 0.5 mM) but was inhibited (maximum 63%) by lysophosphatidylcholine (8 microM). Palmitoyl carnitine (up to 2 mM) was ineffective, but the coenzyme A thioesters of palmitate, stearate, oleate, and arachidonate were inhibitory at concentrations (less than 3 microM) below their critical micellar concentrations. Arachidonyl CoA was approximately one order of magnitude more inhibitory than the other long-chain acyl CoA thioesters. Kinetic analyses revealed the effect of arachidonyl CoA on RINCR activity to be exclusively an alteration of the Vmax with no change in the Km for cytochrome c. The inhibition of myocytic RINCR activity by long-chain acyl CoA may be unrelated to the bulk-phase detergency of this lipid amphiphile since the effects were observed at concentrations below the critical micellar concentration, and other lipid amphiphiles had no effect on RINCR activity. Inhibition of microsomal RINCR activity may result from localized disruption of the membrane microenvironment of the enzyme complex by penetration or dissolution of long-chain acyl CoA into the membrane. The pronounced sensitivity of myocytic RINCR activity to long-chain acyl CoA suggests a relationship between the decreased RINCR activity and the increased levels of this class of lipid metabolites observed in the ischemic myocardium.
F F Kennett, and
T E Knauer, and
K Owens, and
W B Weglicki
October 1978,
Biochimica et biophysica acta,
F F Kennett, and
T E Knauer, and
K Owens, and
W B Weglicki
January 1980,
Journal of biochemistry,
F F Kennett, and
T E Knauer, and
K Owens, and
W B Weglicki
May 1971,
Biochemical and biophysical research communications,
F F Kennett, and
T E Knauer, and
K Owens, and
W B Weglicki
September 1977,
Revista espanola de fisiologia,
F F Kennett, and
T E Knauer, and
K Owens, and
W B Weglicki
January 1974,
Acta biochimica Polonica,
F F Kennett, and
T E Knauer, and
K Owens, and
W B Weglicki
August 1979,
Biochemical Society transactions,
F F Kennett, and
T E Knauer, and
K Owens, and
W B Weglicki
January 2004,
Biofizika,
F F Kennett, and
T E Knauer, and
K Owens, and
W B Weglicki
May 1964,
Science (New York, N.Y.),
F F Kennett, and
T E Knauer, and
K Owens, and
W B Weglicki
January 1978,
Planta,
F F Kennett, and
T E Knauer, and
K Owens, and
W B Weglicki
January 1972,
Bollettino dell'Istituto sieroterapico milanese,
