Acta Biochimica et Biophysica 12. (1977)

1977 / 3. szám - Sándor, A.-Kerner, J.-Alkonyi, I.: Effect of Biguanide (Buformin) on Carnitine Polmitoyltransferase Activity

Acta Biochim. et Biophys. Acad. Sei. Hung. Vol. 12 (3), pp. 217—221 (1977) Effect of a Biguanide (Buformin) on Carnitine Palmitoyltransferase Activity A. Sándor, J. Klrner, I. Alkonyi Biochemical Institute, University Medical School, Pécs, Hungary (Received September 15, 1976) Buformin at a concentration of 1 — 2.5 mM stimulates solubilized carnitine palmitoyltransferase by reducing the inhibitory effect of palmitoyl-CoA. Neither buformin nor metformin inhibits the solubilized carnitine palmitoyltransferase. Introduction It is well established that the reaction catalyzed by CPT, (palmitoyl-CoA; L-carnitine O-palmitoyltransferase; EC 2.3.1.21) is a rate-limiting step in fatty acid oxidation and may be a key regulatory site (Fritz, 1968; Williamson et ah, 1968; Lee, Fritz, 1971; McGarry et ah, 1973; McGarry, Forster 1974; McGarry et ah, 1975). Inhibitors of CPT (-h)-octanoylcarnitine, ( + )-decanoylcarnitine inhibit fatty acid oxidation and ketone body production and can restore the metabolic pattern in the liver from fasted animals (Williamson et ah, 1968; McGarry et ah, 1973; McGarry, Foster, 1974). One may suggest that other anti­­ketotic and antidiabetic agents, such as biguanides, may act at this site. The finding that biguanides inhibit fatty acid oxidation (Muntoni et ah, 1970; Corsini et ah, 1974) supports this view. Although many elfects of these antidiabetic drugs have been recorded, the primary target of their action is not yet known. In an attempt to ascertain the molecular site of attack, we tested whether buformin and metfor­min had any effect on CPT. Materials and methods The enzyme was prepared from bovine liver and was tested as described by Norum (1964) except that the enzyme unit was determined at 25 °C. Enzyme activity was followed in three ways: Radioactive exchange method to measure the CoA-dependent incorporation of L-(3H) carnitine into palmitoylcarnitine (Bremer, Norum, 1967/a). Samples were dissolved in Bray’s scintillation coctail. Abbreviations used: CPT; carnitine palmitoyltransferase. Acta Biochimica et Biophysica Academiae Scientiarum Hungaricae 12, 1977

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