Microsomal malonyl-CoA-sensitive carnitine acyltransferase

2001 ◽  
Vol 29 (1) ◽  
pp. A2-A2
Author(s):  
E. D. Saggerson
Keyword(s):  
Carnitine Acyltransferase ◽  
Malonyl Coa

scholarly journals Importance of experimental conditions in evaluating the malonyl-CoA sensitivity of liver carnitine acyltransferase. Studies with fed and starved rats

1981 ◽  
Vol 200 (2) ◽  
pp. 217-223 ◽  
Author(s):  
J D McGarry ◽  
D W Foster
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Rat Liver ◽  
Competitive Inhibition ◽  
Physiological Role ◽  
Rat Liver Mitochondria ◽  
Acid Oxidation ◽  
Carnitine Acyltransferase ◽  
Malonyl Coa

The experiments reconfirm the powerful inhibitory effect of malonyl-CoA on carnitine acyltransferase I and fatty acid oxidation in rat liver mitochondria (Ki 1.5 microM). Sensitivity decreased with starvation (Ki after 18 h starvation 3.0 microM, and after 42 h 5.0 microM). Observations by Cook, Otto & Cornell [Biochem. J. (1980) 192, 955--958] and Ontko & Johns [Biochem. J. (1980) 192, 959--962] have cast doubt on the physiological role of malonyl-CoA in the regulation of hepatic fatty acid oxidation and ketogenesis. The high Ki values obtained in the cited studies are shown to be due to incubation conditions that cause substrate depletion, destruction of malonyl-CoA or generation of excessively high concentrations of unbound acyl-CoA (which offsets the competitive inhibition of malonyl-CoA towards carnitine acyltransferase I). The present results are entirely consistent with the postulated role of malonyl-CoA as the primary regulatory of fatty acid synthesis and oxidation in rat liver.

scholarly journals Effect of membrane environment on the activity and inhibitability by malonyl-CoA of the carnitine acyltransferase of hepatic microsomal membranes

1997 ◽  
Vol 322 (2) ◽  
pp. 435-440 ◽  
Author(s):  
Neil M. BROADWAY ◽  
E. David SAGGERSON
Keyword(s):  
Lipid Composition ◽  
Membrane Lipids ◽  
Specific Activity ◽  
Membrane Lipid ◽  
Microsomal Membrane ◽  
Membrane Lipid Composition ◽  
Carnitine Acyltransferase ◽  
Malonyl Coa ◽  
Microsomal Membranes ◽  
Myristoyl Coa

We have investigated the extent to which membrane environment affects the catalytic properties of the malonyl-CoA-sensitive carnitine acyltransferase of liver microsomal membranes. Arrhenius-type plots of activity were linear in the absence and presence of malonyl-CoA (2.5 μM). Sensitivity to malonyl-CoA increased with decreasing assay temperature. Partly purified enzyme displayed an increased K0.5 (substrate concentration supporting half the maximal reaction rate) for myristoyl-CoA and a reduced sensitivity to malonyl-CoA compared with the enzyme in situ in membranes. Reconstitution with liposomes of a range of compositions restored the K0.5 for myristoyl-CoA to values similar to that seen in native membranes. The lipid requirements for restoration of sensitivity to malonyl-CoA were more stringent. When animals were starved for 24 h the specific activity of carnitine acyltransferase in microsomal membrane residues was increased 3.3-fold, whereas sensitivity to malonyl-CoA was decreased to 1/2.8. When enzymes partly purified from fed and starved animals were reconstituted into crude soybean phosphatidylcholine liposomes there was no difference in sensitivity to malonyl-CoA. When partly purified enzyme from fed rats was reconstituted into liposomes prepared from microsomal membrane lipids from fed animals it was 2.2-fold more sensitive to malonyl-CoA than when reconstituted with liposomes prepared from microsomal membrane lipids from starved animals. This suggests that the physiological changes in sensitivity to malonyl-CoA are mediated via changes in membrane lipid composition rather than via modification of the enzyme protein itself. The increased specific actvity of acyltransferase observed on starvation could not be attributed to changes in membrane lipid composition.

Lipogenesis in response to an oral glucose load in fed and starved rats

1981 ◽  
Vol 1 (6) ◽  
pp. 469-476 ◽  
Author(s):  
Mary C. Sugden ◽  
David L. Watts ◽  
Christopher E. Marshall
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Brown Fat ◽  
Oral Glucose ◽  
Oral Glucose Load ◽  
Glucose Load ◽  
Palmitoyl Carnitine ◽  
Carnitine Acyltransferase ◽  
Malonyl Coa ◽  
Brown Adipose

Lipogenesis in livers of fed but not of starved rats is increased after intragastric feeding with glucose. In contrast, lipogenesis in brown adipose tissue increases in both fed and starved animals. These observations suggest that lipogenesis in brown adipose tissue is regulated by mechanisms in addition to, or other than, those operating in liver. The fate of newly synthesized lipid in brown adipose tissue is not known. However, the formation of palmitoyl-carnitine from palmitoyl-CoA and carnitine by mitochondria from brown fat was inhibited by malonyl-CoA. Although inhibition was not 100%, it is implied that mitochondrial uptake of the newly synthesized fat by the carnitine acyltransferase system is restricted under conditions of increased lipogenesis.

Muscle malonyl-CoA decreases during exercise

1989 ◽  
Vol 67 (6) ◽  
pp. 2230-2233 ◽  
Author(s):  
W. W. Winder ◽  
J. Arogyasami ◽  
R. J. Barton ◽  
I. M. Elayan ◽  
P. R. Vehrs
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Plasma Catecholamines ◽  
Male Rats ◽  
Acid Oxidation ◽  
Glycogen Depletion ◽  
Carnitine Acyltransferase ◽  
Malonyl Coa ◽  
Important Regulator ◽  
Exercise Induced

Malonyl-CoA, the inhibitor of carnitine acyltransferase I, is an important regulator of fatty acid oxidation and ketogenesis in the liver. Muscle carnitine acyltransferase I has previously been reported to be more sensitive to malonyl-CoA inhibition than is liver carnitine acyltransferase I. Fluctuations in malonyl-CoA concentration may therefore be important in regulating the rate of fatty acid oxidation in muscle during exercise. Male rats were anesthetized (pentobarbital via venous catheters) at rest or after 30 min of treadmill exercise (21 m/min, 15% grade). The gastrocnemius/plantaris muscles were frozen at liquid N2 temperature. Muscle malonyl-CoA decreased from 1.66 +/- 0.17 to 0.60 +/- 0.05 nmol/g during the exercise. This change was accompanied by a 31% increase in cAMP in the muscle. The decline in malonyl-CoA occurred before muscle glycogen depletion and before onset of hypoglycemia. Plasma catecholamines, corticosterone, and free fatty acids were all significantly increased during the exercise. This exercise-induced decrease in malonyl-CoA may be important for allowing the increase in muscle fatty acid oxidation during exercise.

scholarly journals High sensitivity of carnitine acyltransferase I to malonyl-CoA inhibition in liver of obese Zucker rats

FEBS Letters ◽  
1985 ◽  
Vol 182 (2) ◽  
pp. 331-334 ◽  
Author(s):  
Pierre Clouet ◽  
Catherine Henninger ◽  
Marc Pascal ◽  
Jean Bézard
Keyword(s):  
High Sensitivity ◽  
Zucker Rats ◽  
Carnitine Acyltransferase ◽  
Malonyl Coa ◽  
Obese Zucker Rats

scholarly journals Oxidative metabolism of long-chain fatty acids in mitochondria from sheep and rat liver. Evidence that sheep conserve linoleate by limiting its oxidation

1985 ◽  
Vol 225 (1) ◽  
pp. 233-237 ◽  
Author(s):  
J C W Reid ◽  
D R Husbands
Keyword(s):  
Rat Liver ◽  
Specific Activity ◽  
Liver Mitochondria ◽  
Rat Liver Mitochondria ◽  
Beta Oxidation ◽  
Sheep Liver ◽  
Carnitine Acyltransferase ◽  
Malonyl Coa ◽  
Tightly Coupled ◽  
Important Regulator

Mitochondria isolated from the livers of sheep and rats were shown to oxidize palmitate, oleate and linoleate in a tightly coupled manner, by monitoring the oxygen consumption associated with the degradation of these acids in the presence of 2mM-L-malate. Rat liver mitochondria oxidized linoleate and oleate at a rate 1.2-1.8 times that of palmitate. Sheep liver mitochondria had a specific activity for the oxidation of palmitate that was 50-80% of that of rats and a specific activity for the oxidation of oleate and linoleate that was 30-40% that of rats. This would indicate that sheep conserved linoleate by limiting its oxidation. Carnitine acyltransferase I (CAT I) actively esterified palmitoyl-CoA and linoleate to carnitine in both rat and sheep liver mitochondria, and in both cases the rate for linoleate was faster than for palmitate. The CAT I reaction in both rat and sheep liver was inhibited by micromolar amounts of malonyl-CoA. With 90 microM-palmitoyl-CoA as substrate, CAT I was inhibited by 50% with 2.5 microM-malonyl-CoA in rats, and in sheep, 50% inhibition was found with all malonyl-CoA concentrations tested (1-5 microM). With 90 microM-linoleate as substrate for CAT I, a much larger difference in response to malonyl-CoA was seen, the rat enzyme being 50% inhibited at 22 microM-malonyl-CoA, whereas sheep liver CAT I was 91% and 98% inhibited at 1 microM- and 5 microM-malonyl-CoA respectively. We propose that malonyl-CoA may act as an important regulator of beta-oxidation in sheep, discriminating against the use of linoleate as an energy-yielding substrate.

scholarly journals Solubilization and separation of two distinct carnitine acyltransferases from hepatic microsomes: characterization of the malonyl-CoA-sensitive enzyme

1995 ◽  
Vol 310 (3) ◽  
pp. 989-995 ◽  
Author(s):  
N M Broadway ◽  
E D Saggerson
Keyword(s):  
Acyl Chain ◽  
Gel Filtration ◽  
Physiological Role ◽  
Fatty Acyl ◽  
Exchange Chromatography ◽  
Mitochondrial Outer Membrane ◽  
Fatty Acyl Chain ◽  
Acyltransferase Activity ◽  
Carnitine Acyltransferase ◽  
Malonyl Coa

Conditions have been developed for the solubilization of hepatic microsomal carnitine acyltransferase activity in good yield, with excellent long-term stability and with retention of malonyl-CoA sensitivity. Solubilized microsomal carnitine acyltransferase activity can be separated into malonyl-CoA-sensitive and -insensitive activities either by gel filtration on Superdex 200 or by anion-exchange chromatography on Resource Q. On gel filtration the apparent molecular masses of the malonyl-CoA-sensitive and -insensitive activities are approx. 300 kDa and 60 kDa respectively. The malonyl-CoA-sensitive and -insensitive activities have different fatty-acyl-chain-length specificities and different stabilities in the detergent octyl glucoside. Together these findings indicate that the malonyl-CoA-sensitive and -insensitive activities are due to different enzymes. The malonyl-CoA sensitivity of the inhibitable enzyme is markedly increased on reconstitution into soybean L-alpha-lecithin liposomes, demonstrating that phospholipids play a crucial role in the inhibition by this metabolite. Evidence is also provided that the malonyl-CoA-sensitive microsomal carnitine acyltransferase is a different enzyme from the malonyl-CoA-sensitive carnitine palmitoyltransferase found in the mitochondrial outer membrane. The possible physiological role of the two microsomal acyltransferases is discussed.

scholarly journals The effect of malonyl-CoA on overt and latent carnitine acyltransferase activities in rat liver and adipocyte mitochondria

1983 ◽  
Vol 210 (2) ◽  
pp. 591-597 ◽  
Author(s):  
E D Saggerson ◽  
C A Carpenter
Keyword(s):  
Rat Liver ◽  
Liver Mitochondria ◽  
Carnitine Palmitoyltransferase ◽  
Nitrobenzoic Acid ◽  
Carnitine Acyltransferase ◽  
Malonyl Coa ◽  
Before And After ◽  
Carnitine Palmitoyltransferase Activity

1. Carnitine palmitoyltransferase and carnitine octanoyltransferase activities were measured in mitochondria at various acyl-CoA concentrations before and after sonication, thus permitting assessment of both overt and latent activities. 2. Overt carnitine palmitoyltransferase in liver and adipocyte mitochondria and overt carnitine octanoyltransferase in liver mitochondria were inhibited by malonyl-CoA. None of the latent activities were affected by this metabolite. 3. 5,5′-Dithiobis-(2-nitrobenzoic acid) stimulated latent hepatic carnitine palmitoyltransferase at low [palmitoyl-CoA]. 4. Starvation (24 h) decreased overt carnitine palmitoyltransferase activity in adipocyte mitochondria, but did not alter the sensitivity of this activity to malonyl-CoA.

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