Abstract
Hepatic mitochondrial carnitine palmitoyltransferase (CPT) properties, beta-oxidation of palmitoyl-CoA and membrane polarization were measured in lean and obese Zucker rats. The Vmax. of the 'outer' carnitine palmitoyltransferase ('CPT-A') increased with starvation, with no change in the Km for either carnitine or palmitoyl-CoA. The Ki for malonyl-CoA increased with starvation in lean rats, but not in obese rats. The Vmax. of the 'inner' enzyme ('CPT-B'), as measured by using inverted submitochondrial vesicles, increased with starvation in obese rats only, with no change in the Km for either carnitine or palmitoyl-CoA. The Ki for malonyl-CoA was 2-5-fold higher in inverted vesicles than in intact mitochondria, and showed no alteration with starvation. The activities of both enzymes correlated positively with each other and with beta-oxidation, and inversely with membrane polarization. Malonyl-CoA had little effect on gross membrane fluidity in the Zucker rat, as reflected by diphenylhexatriene fluorescence polarization. The results indicate that both enzymes are related and respond similarly to alterations in membrane fluidity. Membrane fluidity may provide a mechanism for co-ordinated control of CPT activity on both sides of the mitochondrial inner membrane.
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Selected References
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- Bergstrom J. D., Reitz R. C. Studies on carnitine palmitoyl transferase: the similar nature of CPTi (inner form) and CPTo (outer form). Arch Biochem Biophys. 1980 Oct 1;204(1):71–79. doi: 10.1016/0003-9861(80)90008-9. [DOI] [PubMed] [Google Scholar]
- Brady L. J., Hoppel C. L. Effect of diet and starvation on hepatic mitochondrial function in the rat. J Nutr. 1983 Nov;113(11):2129–2137. doi: 10.1093/jn/113.11.2129. [DOI] [PubMed] [Google Scholar]
- Brady L. J., Hoppel C. L. Hepatic mitochondrial function in lean and obese Zucker rats. Am J Physiol. 1983 Sep;245(3):E239–E245. doi: 10.1152/ajpendo.1983.245.3.E239. [DOI] [PubMed] [Google Scholar]
- Bremer J. The effect of fasting on the activity of liver carnitine palmitoyltransferase and its inhibition by malonyl-CoA. Biochim Biophys Acta. 1981 Sep 24;665(3):628–631. doi: 10.1016/0005-2760(81)90282-4. [DOI] [PubMed] [Google Scholar]
- Clarke P. R., Bieber L. L. Isolation and purification of mitochondrial carnitine octanoyltransferase activities from beef heart. J Biol Chem. 1981 Oct 10;256(19):9861–9868. [PubMed] [Google Scholar]
- Clejan S., Collipp P. J., Maddaiah V. T. Hormones and liver mitochondria: influence of growth hormone, thyroxine, testosterone, and insulin on thermotropic effects of respiration and fatty acid composition of membranes. Arch Biochem Biophys. 1980 Sep;203(2):744–752. doi: 10.1016/0003-9861(80)90234-9. [DOI] [PubMed] [Google Scholar]
- Clouet P., Henninger C., Pascal M., Bézard J. High sensitivity of carnitine acyltransferase I to malonyl-CoA inhibition in liver of obese Zucker rats. FEBS Lett. 1985 Mar 25;182(2):331–334. doi: 10.1016/0014-5793(85)80327-6. [DOI] [PubMed] [Google Scholar]
- Cook G. A. Differences in the sensitivity of carnitine palmitoyltransferase to inhibition by malonyl-CoA are due to differences in Ki values. J Biol Chem. 1984 Oct 10;259(19):12030–12033. [PubMed] [Google Scholar]
- Cook G. A., Stephens T. W., Harris R. A. Altered sensitivity of carnitine palmitoyltransferase to inhibition by malonyl-CoA in ketotic diabetic rats. Biochem J. 1984 Apr 1;219(1):337–339. doi: 10.1042/bj2190337. [DOI] [PMC free article] [PubMed] [Google Scholar]
- DiMarco J. P., Hoppel C. Hepatic mitochondrial function in ketogenic states. Diabetes, starvation, and after growth hormone administration. J Clin Invest. 1975 Jun;55(6):1237–1244. doi: 10.1172/JCI108042. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fleischer S., Meissner G., Smigel M., Wood R. Preparation of submitochondrial vesicles using nitrogen decompression. Methods Enzymol. 1974;31:292–299. doi: 10.1016/0076-6879(74)31030-0. [DOI] [PubMed] [Google Scholar]
- Gordon L. M., Sauerheber R. D., Esgate J. A., Dipple I., Marchmont R. J., Houslay M. D. The increase in bilayer fluidity of rat liver plasma membranes achieved by the local anesthetic benzyl alcohol affects the activity of intrinsic membrane enzymes. J Biol Chem. 1980 May 25;255(10):4519–4527. [PubMed] [Google Scholar]
- Hanson R. W., Ballard F. J. Citrate, pyruvate, and lactate contaminants of commercial serum albumin. J Lipid Res. 1968 Sep;9(5):667–668. [PubMed] [Google Scholar]
- Harano Y., Kosugi K., Kashiwagi A., Nakano T., Hidaka H., Shigeta Y. Regulatory mechanism of ketogenesis by glucagon and insulin in isolated and cultured hepatocytes. J Biochem. 1982 May;91(5):1739–1748. doi: 10.1093/oxfordjournals.jbchem.a133866. [DOI] [PubMed] [Google Scholar]
- Harano Y., Kowal J., Yamazaki R., Lavine L., Miller M. Carnitine palmitoyltransferase activities (1 and 2) and the rate of palmitate oxidation in liver mitochondria from diabetic rats. Arch Biochem Biophys. 1972 Dec;153(2):426–437. doi: 10.1016/0003-9861(72)90360-8. [DOI] [PubMed] [Google Scholar]
- Hoppel C. L. Carnitine and carnitine palmitoyltransferase in fatty acid oxidation and ketosis. Fed Proc. 1982 Oct;41(12):2853–2857. [PubMed] [Google Scholar]
- Hoppel C. L., Tomec R. J. Carnitine palmityltransferase. Location of two enzymatic activities in rat liver mitochondria. J Biol Chem. 1972 Feb 10;247(3):832–841. [PubMed] [Google Scholar]
- Hoppel C., DiMarco J. P., Tandler B. Riboflavin and rat hepatic cell structure and function. Mitochondrial oxidative metabolism in deficiency states. J Biol Chem. 1979 May 25;254(10):4164–4170. [PubMed] [Google Scholar]
- McGarry J. D., Foster D. W. Regulation of hepatic fatty acid oxidation and ketone body production. Annu Rev Biochem. 1980;49:395–420. doi: 10.1146/annurev.bi.49.070180.002143. [DOI] [PubMed] [Google Scholar]
- McGarry J. D., Leatherman G. F., Foster D. W. Carnitine palmitoyltransferase I. The site of inhibition of hepatic fatty acid oxidation by malonyl-CoA. J Biol Chem. 1978 Jun 25;253(12):4128–4136. [PubMed] [Google Scholar]
- McMurchie E. J., Abeywardena M. Y., Charnock J. S., Gibson R. A. Differential modulation of rat heart mitochondrial membrane-associated enzymes by dietary lipid. Biochim Biophys Acta. 1983 Oct 4;760(1):13–24. doi: 10.1016/0304-4165(83)90119-8. [DOI] [PubMed] [Google Scholar]
- McMurchie E. J., Abeywardena M. Y., Charnock J. S., Gibson R. A. The effect of dietary lipids on the thermotropic behaviour of rat liver and heart mitochondrial membrane lipids. Biochim Biophys Acta. 1983 Sep 21;734(1):114–124. doi: 10.1016/0005-2736(83)90082-2. [DOI] [PubMed] [Google Scholar]
- McMurchie E. J., Gibson R. A., Abeywardena M. Y., Charnock J. S. Dietary lipid modulation of rat liver mitochondrial succinate: cytochrome c reductase. Biochim Biophys Acta. 1983 Jan 5;727(1):163–169. doi: 10.1016/0005-2736(83)90380-2. [DOI] [PubMed] [Google Scholar]
- Mills S. E., Foster D. W., McGarry J. D. Effects of pH on the interaction of substrates and malonyl-CoA with mitochondrial carnitine palmitoyltransferase I. Biochem J. 1984 Apr 15;219(2):601–608. doi: 10.1042/bj2190601. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Prendergast F. G., Haugland R. P., Callahan P. J. 1-[4-(Trimethylamino)phenyl]-6-phenylhexa-1,3,5-triene: synthesis, fluorescence properties, and use as a fluorescence probe of lipid bilayers. Biochemistry. 1981 Dec 22;20(26):7333–7338. doi: 10.1021/bi00529a002. [DOI] [PubMed] [Google Scholar]
- Saggerson E. D., Bird M. I., Carpenter C. A., Winter K. A., Wright J. J. Cycloheximide blocks changes in rat liver carnitine palmitoyltransferase 1 activity in starvation. Biochem J. 1984 Nov 15;224(1):201–206. doi: 10.1042/bj2240201. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Saggerson E. D., Carpenter C. A., Tselentis B. S. Effects of thyroidectomy and starvation on the activity and properties of hepatic carnitine palmitoyltransferase. Biochem J. 1982 Dec 15;208(3):667–672. doi: 10.1042/bj2080667. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sandermann H., Jr Regulation of membrane enzymes by lipids. Biochim Biophys Acta. 1978 Sep 29;515(3):209–237. doi: 10.1016/0304-4157(78)90015-1. [DOI] [PubMed] [Google Scholar]
- Stakkestad J. A., Bremer J. The outer carnitine palmitoyltransferase and regulation of fatty acid metabolism in rat liver in different thyroid states. Biochim Biophys Acta. 1983 Feb 7;750(2):244–252. doi: 10.1016/0005-2760(83)90025-5. [DOI] [PubMed] [Google Scholar]
- Stubbs C. D., Kinosita K., Jr, Munkonge F., Quinn P. J., Ikegami A. The dynamics of lipid motion in sarcoplasmic reticulum membranes determined by steady-state and time-resolved fluorescence measurements on 1,6-diphenyl-1,3,5-hexatriene and related molecules. Biochim Biophys Acta. 1984 Sep 5;775(3):374–380. doi: 10.1016/0005-2736(84)90193-7. [DOI] [PubMed] [Google Scholar]
- Vidal J. C., McIntyre J. O., Churchill P., Andrew J. A., Péhuet M., Fleischer S. Influence of diabetes on rat liver mitochondria: decreased unsaturation of phospholipid and D-beta-hydroxybutyrate dehydrogenase activity. Arch Biochem Biophys. 1983 Jul 15;224(2):643–658. doi: 10.1016/0003-9861(83)90252-7. [DOI] [PubMed] [Google Scholar]
- York D. A., Hyslop P. A., French R. Fluorescence polarisation and composition of membranes in genetic obesity. Biochem Biophys Res Commun. 1982 Jun 30;106(4):1478–1453. doi: 10.1016/0006-291x(82)91280-3. [DOI] [PubMed] [Google Scholar]