TY - JOUR
T1 - Characteristics of fatty acid oxidation in rat liver homogenates and the inhibitory effect of malonyl-CoA
AU - McGarry, J. Denis
AU - Mannaerts, Guy P.
AU - Foster, Daniel W.
N1 - Funding Information:
The expert technical assistanceo f Ms. Martha Bennett and Petra Contreras is gratefully acknowledged. This work was supported by United States Public Health Service Grant AM-18573 and Training Grant CA-05200. J.D.M. is
PY - 1978/9/28
Y1 - 1978/9/28
N2 - Experiments were carried out to study the control of fatty acid oxidation and ketogenesis in rat liver homogenates. In contrast to findings with the perfused liver, rates of fatty acid oxidation were high and equal in liver homogenates from fed and fasted animals. No difference in apparent Km values for oleate, ATP, coenzyme A or carnitine could be detected in the two types of homogenate. Over the concentration range 25-40 μM, malonyl-CoA inhibited oleate oxidation by 50-75%. The fact that the inhibitory effect could be removed by pre-treatment with alkali or fatty acid synthetase indicated that the inhibitory molecule was malonyl-CoA rather than a contaminant. The effect was readily reversible and appeared to be competitive with oleyl-CoA. Malonyl-CoA also inhibited oleate oxidation in homogenates of heart and kidney cortex but this is unlikely to have physiological relevance since, in contrast to liver, neither tissue contains an active cytosolic pathway for the generation of malonyl-CoA and the synthesis of fatty acids.
AB - Experiments were carried out to study the control of fatty acid oxidation and ketogenesis in rat liver homogenates. In contrast to findings with the perfused liver, rates of fatty acid oxidation were high and equal in liver homogenates from fed and fasted animals. No difference in apparent Km values for oleate, ATP, coenzyme A or carnitine could be detected in the two types of homogenate. Over the concentration range 25-40 μM, malonyl-CoA inhibited oleate oxidation by 50-75%. The fact that the inhibitory effect could be removed by pre-treatment with alkali or fatty acid synthetase indicated that the inhibitory molecule was malonyl-CoA rather than a contaminant. The effect was readily reversible and appeared to be competitive with oleyl-CoA. Malonyl-CoA also inhibited oleate oxidation in homogenates of heart and kidney cortex but this is unlikely to have physiological relevance since, in contrast to liver, neither tissue contains an active cytosolic pathway for the generation of malonyl-CoA and the synthesis of fatty acids.
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U2 - 10.1016/0005-2760(78)90150-9
DO - 10.1016/0005-2760(78)90150-9
M3 - Article
C2 - 698234
AN - SCOPUS:0018126246
SN - 0005-2760
VL - 530
SP - 305
EP - 313
JO - Biochimica et Biophysica Acta (BBA)/Lipids and Lipid Metabolism
JF - Biochimica et Biophysica Acta (BBA)/Lipids and Lipid Metabolism
IS - 3
ER -