A possible role for malonyl-CoA in the regulation of hepatic fatty acid oxidation and ketogenesis.
نویسندگان
چکیده
Studied on the oxidation of oleic and octanoic acids to ketone bodies were carried out in homogenates and in mitochondrial fractions of livers taken from fed and fasted rats. Malonyl-CoA inhibited ketogenesis from the former but not from the latter substrate. The site of inhibition appeared to be the carnitine acyltransferase I reaction. The effect was specific and easily reversible. Inhibitory concentrations were in the range of values obtained in livers from fed rats by others. It is proposed that malonyl-CoA functions as both precursor for fatty acid synthesis and suppressor of fatty acid oxidation. As such, it might be an important element in the carbohydrate-induced sparing of fatty acid oxidation.
منابع مشابه
In support of the roles of malonyl-CoA and carnitine acyltransferase I in the regulation of hepatic fatty acid oxidation and ketogenesis.
The rate of fatty acid synthesis in hepatocytes from meal-fed rats was manipulated over a wide range using glucose, lactate, and pyruvate to drive the system maximally, and glucagon, 5-(tetradecyloxy)-2-furoic acid (RMI 14,514), or a combination of both agents to inhibit lipogenesis. Measurements were made of cellular malonyl-CoA levels, long chain acylcarnitine concentration, and [l-‘4C]oleate...
متن کاملImportance of experimental conditions in evaluating the malonyl-CoA sensitivity of liver carnitine acyltransferase. Studies with fed and starved rats.
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--96...
متن کاملMalonyl-CoA and carnitine palmitoyltransferase I: an expanding partnership.
Inhibition of mitochondrial carnitine palmitoyltransferase I (CPT I) by malonyl-CoA, the product of the acetyl-CoA carboxylase reaction, was first recognized in 1977 during the course of studies on hepatic ketogenesis and its regulation [ l ] . What emerged from that work was that with carbohydrate feeding (high insulin/low glucagon) the liver is actively engaged in fatty acid biosynthesis, the...
متن کاملInhibition by acetyl-CoA of hepatic carnitine acyltransferase and fatty acid oxidation.
At micromolar concentrations, acetyl-CoA inhibited hepatic carnitine acyltransferase activity and mitochondrial fatty acid oxidation. The inhibitory effects were not nearly as potent on a molar basis as those of malonyl-CoA; nevertheless, the cytosolic concentrations of acetyl-CoA, as yet unknown, may be sufficient (greater than 30 microM) to curtail appreciably the mitochondrial transfer of lo...
متن کاملThe role of the carnitine system in human metabolism.
Metabolism cycles daily between the fed and fasted states. The pathways of energy production are reversible and distinct. In the anabolic (fed) state, the liver stores glucose as glycogen, and fatty acid/triglyceride synthesis is active. In the catabolic (fasted) state, the liver becomes a glucose producer, lipogenesis is slowed, and fatty acid oxidation/ketogenesis is activated. The rate-limit...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- The Journal of clinical investigation
دوره 60 1 شماره
صفحات -
تاریخ انتشار 1977