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Carnitine palmitoyltransferase activities: Effects of serum albumin, acyl-CoA binding protein and fatty acid binding protein

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Abstract

The carnitine palmitoyltransferase activity of various subcellular preparations measured with octanoyl-CoA as substrate was markedly increased by bovine serum albumin at low μM concentrations of octanoyl-CoA. However, even a large excess (500 μM) of this acyl-CoA did not inhibit the activity of the mitochondrial outer carnitine palmitoyltransferase, a carnitine palmitoyltransferase isoform that is particularly sensitive to inhibition by low μM concentrations of palmitoyl-CoA. This bovine serum albumin stimulation was independent of the salt activation of the carnitine palmitoyltransferase activity. The effects of acyl-CoA binding protein (ACBP) and the fatty acid binding protein were also examined with palmitoyl-CoA as substrate. The results were in line with the findings of stronger binding of acyl-CoA to ACBP but showed that fatty acid binding protein also binds acyl-CoA esters. Although the effects of these proteins on the outer mitochondrial carnitine palmitoyltransferase activity and its malonyl-CoA inhibition varied with the experimental conditions, they showed that the various carnitine palmitoyltransferase preparations are effectively able to use palmitoyl-CoA bound to ACBP in a near physiological molar ratio of 1:1 as well as that bound to the fatty acid binding protein. It is suggested that the three proteins mentioned above effect the carnitine palmitoyltransferase activities not only by binding of acyl-CoAs, preventing acyl-CoA inhibition, but also by facilitating the removal of the acylcarnitine product from carnitine palmitoyltransferase. These results support the possibility that the acyl-CoA binding ability of acyl-CoA binding protein and of fatty acid binding protein have a role in acyl-CoA metabolismin vivo.

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Abbreviations

ACBP:

acyl-CoA binding protein

BSA:

bovine serum albumin

CPT:

carnitine palmitoyltransferase

CPT0 :

malonyl-CoA sensitive CPT of the outer mitochondrial membrane

CPT:

malonyl-CoA insensitive CPT of the inner mitochondrial membrane

OG:

octylglucoside

OMV:

outer membrane vesicles

IMV:

inner membrane vesicles

References

  1. Bremer J, Norum KR: The mechanism of substrate inhibition of palmityl coenzyme A: carnitine palmityltransferase by palmityl coenzyme A. J Biol Chem 242: 1744–1748, 1967

    PubMed  Google Scholar 

  2. McGarry JD, Leatherman GH, Foster DW: Carnitine palmitoyl-transferase I. The site of inhibition of hepatic fatty acid oxidation by malonyl-CoA. J Biol Chem 253: 4128–4136

  3. Murthy MSR, Pande SV: Some differences in the properties of carnitine palmitoyltransferase activities of the mitochondrial outer and the inner membranes. Biochem. J 248: 727–733, 1987

    PubMed  Google Scholar 

  4. Knudsen J: Acyl-CoA-binding protein (ACBP) and its relation to fatty acid-binding protein (FABP): an overview (review). Mol Cell Biochem 98: 217–223, 1990

    PubMed  Google Scholar 

  5. Knudsen J: Acyl-CoA-binding and transport, an alternative function for diazepam binding inhibitor (DBI), which is identical with acyl-CoA-binding protein. Neuropharmacology 30: 1405–1410, 1991

    PubMed  Google Scholar 

  6. Ockner RR: Historic overview of studies on fatty acid-binding proteins (review). Mol Cell Biochem 98: 3–9, 1990

    PubMed  Google Scholar 

  7. Bhuiyan AKMJ, Pande S.V.: Unexpected stimulation of carnitine palmitoyltransferase activities by bovine serum albumin with octanoyl-CoA as a substrate. FASEB J 5: Abstr. 1291, 1991

    Google Scholar 

  8. Bhuiyan AKMJ, Pande SV: Stimulation of carnitine palmitoyltransferases activities of different subcellular fraction by acyl-CoA binding protein. In: A. Lee Carter (ed). Current Concepts in carnitine research. CRC Press, 1992, Abstr., p. 191

  9. Bhuiyan AKMJ, Pande SV: One-step synthesis of radioactive acyl-CoA and acylcarnitines using rat liver mitochondrial outer membranes as enzyme source. Lipids 27: 392–395, 1992

    PubMed  Google Scholar 

  10. Hovius R, Lambrechts H, Nicolay K, de Kruijff B: Improved methods to isolate and subfractionate rat liver mitochondria. Lipid composition of the inner and outer membrane. Biochim Biophys Acta 1021: 217–226, 1990

    PubMed  Google Scholar 

  11. Murthy MSR, Pande SV: Malonyl-CoA binding site and the overt carnitine palmitoyltransferase activity reside on the opposite sides of the outer mitochondrial membrane. Proc Natl Acad Sci USA 84: 372–382, 1987

    Google Scholar 

  12. Derrick JP, Ramsay RR: L-carnitine acyltransferase in intact peroxisomes is inhibited by malonyl-CoA. Biochem. J 262: 801–806, 1989

    PubMed  Google Scholar 

  13. Pande SV, Murthy MSR, Noël H: Differential effects of phosphatidylcholine and cardiolipin on carnitine palmitoyltransferase activity. Biochim Biophys Acta 877: 223–230, 1986

    PubMed  Google Scholar 

  14. Murthy MSR, Pande SV: Characterization of a solubilized malonyl-CoA sensitive carnitine palmitoyltransferase from the mitochondrial outer membrane as a protein distinct from the malonyl-CoA-insensitive carnitine palmitoyltransferase of the inner membrane. Biochem J 268, 599–604, 1990

    PubMed  Google Scholar 

  15. Pande SV, Bhuiyan AKJM, Murthy MSR: Carnitine palmitoyl transferases: How many and how to discriminate. In: A.L. Carter (ed). Current Concepts in Carnitine Research, CRC Press, Boca Raton, USA, 1992, pp 165–178

    Google Scholar 

  16. Haunerland N, Jagschies G, Schulenberg H, Spener F: Fatty-acid-binding proteins. Occurrence of two fatty-acid-binding proteins in bovine liver cytosol and their binding of fatty acids, cholesterol, and other lipophilic ligands. Hoppe-Seyler's Z Physiol Chem 365: 365–376, 1984

    PubMed  Google Scholar 

  17. Mikkelsen J, Hojrup P, Nielsen PF, Roepstorff P, Knudsen J: Amino acid sequence of acyl-CoA-binding protein from cow liver. Biochem J 245: 857–861, 1987

    PubMed  Google Scholar 

  18. Knudsen J, Hojrup P, Hansen HO, Hansen HF, Roepstotff P: Acyl-CoA-binding protein in the rat. Purification, binding characteristics, tissue concentrations and amino acid sequence. Biochem J 262: 513–519, 1989

    PubMed  Google Scholar 

  19. Pauly DF, McMillin JB: Importance of acyl-CoA availability in interpretation of carnitine palmitoyltransferase I kinetics. J Biol Chem 263: 18160–18167, 1988

    PubMed  Google Scholar 

  20. Richards EW, Hamm MW, Otto DA: The effect of palmitoyl-CoA binding to albumin on the apparent kinetic behavior of carnitine palmitoyltransferase I. Biochim Biophys Acta 1076: 23–28, 1991

    PubMed  Google Scholar 

  21. A'Bhaird NN, Ramsay RR: Malonyl-CoA inhibition of peroxisomal carnitine octanoyltransferase. Biochem J 286: 637–640, 1992

    PubMed  Google Scholar 

  22. Solberg HE: Different carnitine acyltransferases in calf liver. Biochim Biophys Acta 280: 422–433, 1972

    PubMed  Google Scholar 

  23. Pande SV, Lee T-S, Murthy MSR: ATP-Mg2+ reversal of the salt activation of membrane bound carnitine palmitoyltransferase activities of liver mitochondria. Biochem Int 17: 1021–1028, 1988

    PubMed  Google Scholar 

  24. Grinstead GF, Trzaskos JM, Billheimer JT, Gaylor JL: Cytosolic modulators of activities of microsomal enzymes of cholesterol biosynthesis. Effects of Acyl-CoA inhibition and cytosolic Z-protein. Biochim Biophys Acta 751: 41–51, 1983

    PubMed  Google Scholar 

  25. Glatz JFC, Veerkamp JH: Intracellular fatty acid-binding proteins. Int J Biochem 17: 13–22, 1985

    PubMed  Google Scholar 

  26. Sweetser DA, Heuckeroth RO, Gordon JL: The metabolic significance of mamalian fatty-acid-binding proteins: abundant proteins in search of a function. Ann Rev Nutr 7: 337–359, 1987

    Google Scholar 

  27. Rasmussen JT, Borchers T, Knudsen J: Comparison of the binding affinities of acyl-CoA-binding protein and fatty-acid-binding protein for long-chain acyl-CoA esters. Biochem J 265: 849–855, 1990

    PubMed  Google Scholar 

  28. Brecher P: The interaction of long-chain acyl CoA with memoranes (review). Mol Cell Biochem 57: 3–15, 1983

    PubMed  Google Scholar 

  29. Smith RH, Powell GL: The critical micelle concentration of some physiologically important fatty acyl-coenzyme A's as a function of chain length. Arch Biochem Biophys 244: 357–360, 1986

    PubMed  Google Scholar 

  30. Hoppel CL, Tomec RJ: Carnitine palmityltransferase. Location of two enzymatic activities in rat liver mitochondria. J Biol Chem 247: 832–841, 1972

    PubMed  Google Scholar 

  31. Burrier RE, Manson CR, Brecher P: Binding of acyl-CoA to liver fatty acid binding protein: effect on acyl-CoA synthesis. Biochim Biophys Acta 919: 221–230, 1987

    PubMed  Google Scholar 

  32. Sumper M, Trauble H: Membranes as acceptors for palmitoyl-CoA in fatty acid biosynthesis. FEBS Lett 30: 29–34, 1973

    PubMed  Google Scholar 

  33. Block K: Control mechanisms for fatty acid synthesis in Mycobacterium smegmatis (review). Adv Enzymol 45: 1–84, 1977

    PubMed  Google Scholar 

  34. Khan ZU, Helmkamp GM Jr: Stimulation of cholinephosphotransferase activity by phosphatidylcholine transfer protein. Regulation of membrane phospholipid synthesis by a cytosolic protein. J Biol Chem 265: 700–705, 1990

    PubMed  Google Scholar 

  35. Vancura A, Haldar D: Regulation of mitochondrial and microsomal phospholipid synthesis by liver fatty acid-binding protein. J Biol Chem 267: 1433–14359, 1992

    Google Scholar 

  36. Catala A: Stearic acid desaturation in rat liver microsomes: stimulation by fatty acid binding protein. Acta Physiol Pharmacol Latinoam 36: 19–27, 1986

    PubMed  Google Scholar 

  37. Guidotti A, Forchetti CM, Corda MG, Konkel D, Bennett CD, Costa E: Isolation, characterization, and purification to homogeneity of an endogeneous polypeptide with agonistic action on benzodiazepine receptors. Proc Natl Acad Sci USA 80: 3531–3535, 1983

    PubMed  Google Scholar 

  38. Chen ZW, Agerberth B, Gell K, Anderson M, Mutt V, Ostenson CG, Efendic S, Barros-Soderling J, Persson B, Jornvall H: Isolation and characterization of porcine diazepam-binding inhibitor, a polypeptide not only of cerebral occurrence but also common in intestinal tissues and with effects on regulation of insulin release. Eur J Biochem 174: 239–245, 1988

    PubMed  Google Scholar 

  39. Besman MJ, Yanagibashi K, Lee TD, Kawamura M, Hall PF, Shively JE: Identification of des-(Gly-Ile)-endozepine as an effector of corticotropin-dependent adrenal steroidogenesis: stimulation of cholesterol delivery is mediated by the peripheral benzodiazepine receptor. Proc Natl Acad Sci USA 86: 4897–4901, 1989

    PubMed  Google Scholar 

  40. Mandrup S, Hummel R, Ravn S, Jensen G, Andreasen P, Gregersen N, Knudsen J, Kristiansen K: Acyl-CoA-binding protein/diazepan-binding inhibitor gene and pseudogenes. A typical housekeeping gene family. J Mol Biol 228: 1011–1022, 1992

    PubMed  Google Scholar 

  41. Pande SV, Goswami T, Parvin R: Protective role of adenine nucleotide translocase in O2-deficient hearts. Am J Physiol 247: H25-H34, 1984

    PubMed  Google Scholar 

  42. Rasmussen JT, Rosendal J, Knudsen J: Interaction of acyl CoA binding protein (ACBP) on processes for which acyl-CoA is a substrate, product or inhibitor. Biochem J 292: 907–913, 1993

    PubMed  Google Scholar 

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Author notes

  1. A. K. M. Jalaluddin Bhuiyan

    Present address: Division of Clinical Chemistry, Vancouver General Hospital, V5Z 1M9, B.C., Canada

Authors and Affiliations

  1. Laboratory of Intermediary Metabolism, Clinical Research Institute of Montreal, 110 Pine Avenue West, H2W 1R7, Montreal, Quebec, Canada

    A. K. M. Jalaluddin Bhuiyan & Shri V. Pande

Authors
  1. A. K. M. Jalaluddin Bhuiyan
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  2. Shri V. Pande
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Affiliated to the Department of Experimental Medicine, University of Montreal

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Bhuiyan, A.K.M.J., Pande, S.V. Carnitine palmitoyltransferase activities: Effects of serum albumin, acyl-CoA binding protein and fatty acid binding protein. Mol Cell Biochem 139, 109–116 (1994). https://doi.org/10.1007/BF01081733

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  • DOI: https://doi.org/10.1007/BF01081733

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