scholarly journals Subcellular distribution and characteristics of ciprofibroyl-CoA synthetase in rat liver. Its possible identity with long-chain acyl-CoA synthetase

1992 ◽  
Vol 284 (1) ◽  
pp. 283-287 ◽  
Author(s):  
L Amigo ◽  
M C McElroy ◽  
M N Morales ◽  
M Bronfman
Keyword(s):  
Rat Liver ◽  
Subcellular Distribution ◽  
Liver Microsomes ◽  
Mitochondrial Fraction ◽  
Rat Tissues ◽  
Rat Liver Microsomes ◽  
Freezing And Thawing ◽  
Chain Acyl ◽  
Related Proteins ◽  
Long Chain

The subcellular distribution and characteristics of ciprofibroyl-CoA synthetase were studied in rat liver and compared with those of long-chain acyl-CoA synthetase (palmitate as substrate) which, as already known, is distributed among mitochondria, microsomes and peroxisomes. Upon differential centrifugation, the subcellular distribution of ciprofibroyl-CoA synthetase followed closely that of palmitoyl-CoA synthetase and was specifically inactivated in the mitochondrial fraction by freezing and thawing, a behaviour already described for palmitoyl-CoA synthetase. Both enzyme activities were found to co-purify through several steps from rat liver microsomes. By using a partially purified enzyme, the activation of ciprofibrate to its acyl-CoA ester followed Michaelis-Menten kinetics with an apparent Km of 0.63 +/- 0.1 mM. Ciprofibroyl-CoA synthetase was competitively inhibited by 25 and 50 microM-palmitic acid. Higher concentrations of the fatty acid resulted in a mixed type of inhibition. Conversely, ciprofibrate up to 0.5 mM was found to inhibit competitively palmitoyl-CoA synthetase, whereas higher concentrations also resulted in a mixed inhibition. The highest activity of ciprofibroyl-CoA synthetase was found in fat and liver homogenates. The distribution of the enzyme in different rat tissues was similar to that of palmitoyl-CoA synthetase. The present results suggest that long-chain acyl-CoA synthetase and ciprofibroyl-CoA synthetase activities reside in identical or closely related proteins.

scholarly journals Effects of CoA and acyl-CoA on Ca2+-permeability of endoplasmic-reticulum membranes from rat liver

1995 ◽  
Vol 306 (3) ◽  
pp. 703-708 ◽  
Author(s):  
G T Rich ◽  
J G Comerford ◽  
S Graham ◽  
A P Dawson
Keyword(s):  
Fatty Acids ◽  
Membrane Fusion ◽  
Rat Liver ◽  
Liver Microsomes ◽  
Rat Liver Microsomes ◽  
Short Term ◽  
Esterified Fatty Acids ◽  
Chain Acyl ◽  
Microsomal Membranes ◽  
Long Chain

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.

scholarly journals Activation of a peroxisome-proliferating catabolite of cholic acid to its CoA ester

1993 ◽  
Vol 296 (1) ◽  
pp. 265-270 ◽  
Author(s):  
T Nishimaki-Mogami ◽  
A Takahashi ◽  
Y Hayashi
Keyword(s):  
Cholic Acid ◽  
Rat Liver ◽  
Microsomal Fraction ◽  
Liver Microsomes ◽  
Subcellular Fractionation ◽  
Fatty Acyl ◽  
Peroxisome Proliferator ◽  
Rat Liver Microsomes ◽  
Triton X ◽  
Long Chain

We have shown that a microbial cholic acid catabolite (4R)-4-(2,3,4,6,6a beta,7,8,9,9a alpha,9b beta-decahydro-6a beta-methyl-3-oxo- 1H-cyclopenta[f]quinolin-7 beta-yl)valeric acid (DCQVA), is a potent peroxisome proliferator. In this paper a possible key stage in DCQVA metabolism, the activation of DCQVA to its CoA ester, has been investigated in rat liver microsomes and particulate fractions. The microsomal reaction was dependent on CoA, ATP, DCQVA (0.2-1 mM) and protein content. The reaction was decreased by storage at 4 degrees C, preincubation of microsomes at 37 degrees C for 5 min, or inclusion of Triton X-100 in the reaction mixture. Such treatments also enhanced generation of long-chain fatty acyl-CoAs, as determined by h.p.l.c. analysis. The same effect was caused by exposing the microsomes to phospholipase A2, suggesting that endogenous fatty acids may compete with DCQVA for esterification with CoA. Subcellular fractionation of rat liver demonstrated that the activity of DCQVA-CoA synthesis was localized predominantly in the microsomal fraction, in contrast to long-chain fatty acyl-CoA synthetase, which was distributed among all particulate fractions. Administration of clofibrate of rats did not affect the distribution of DCQVA-CoA synthesis activity. In contrast to a 2-fold induction of long-chain fatty acyl-CoA synthetase by clofibrate treatment, the activity of DCQVA-CoA synthesis in the microsomal fraction decreased by 80%. These results suggest that DCQVA is activated by an enzyme distinct from long-chain fatty acyl-CoA synthetase. The resulting perturbation of fatty acid metabolism may be involved in the mechanism whereby DCQVA causes peroxisome proliferation.

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