Advertisement

Protein Synthesis Studies in Rats with Methionine

  • A. M. Planas
  • C. Prenant
  • B. M. Mazoyer
  • S. Chadan
  • D. Comar
  • L. Digiamberardino
Part of the Developments in Nuclear Medicine book series (DNUM, volume 23)

Abstract

1) Total brain radioactivity was found to be regionally correlated (r = 0.97) with radioactivity incorporated into proteins following a bolus injection of [14C-methyl]methionine. This suggests that regional differences in total label accumulation correspond to differences in the incorporation of label into proteins. 2) Under steady-state conditions (i.e., during continuous infusion of [14C-methyl]methionine), regional brain specific activity (SA) was found to be lower than the plasma SA. Brain SA was diluted by an endogenous source of free methionine likely to be from protein breakdown. Assuming that all endogenous brain methionine can contribute to protein synthesis, measuring labelled methionine incorporation (without accounting for tissue SA), would lead to underestimated rates. 3) In contrast to these results, similar studies carried out on the rat heart have shown a ratio of heart to plasma SA equivalent to unity. According to this, methionine recycling did not became apparent in the heart during the experimental time and under our experimental conditions.

Keywords

Positron Emission Tomography Cereb Blood Flow Protein Breakdown Protein Synthesis Rate Endogenous Source 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Ericson K, Blomqvist G, Bergström M, Eriksson L, Stone-Elander S. Application of a kinetic model on the methionine accumulation in intracranial tumors studied with positron emission tomography. Acta Radiol 1987; 28: 505–509.PubMedCrossRefGoogle Scholar
  2. 2.
    Lestage P, Gonon M, Lepetit P, et al. An in vivo kinetic model with 1-[35S]methionine incorporation into protein in the rat. J Neurochem 1987; 48: 352–363.PubMedCrossRefGoogle Scholar
  3. 3.
    Mazoyer BM, Levasseur M, Syrota A, et al. Modelization of 11C-L-methionine PET kinetics in the brain of fasted and fed humans. J Cereb Blood Flow Metab 1989; 9 (suppl 1): S37.Google Scholar
  4. 4.
    Phelps ME, Barrio JR, Huang S-C, Keen RE, Chugani H, Mazziotta JC. Criteria for the tracer kinetic measurement of cerebral protein synthesis in humans with positron emission tomography. Ann Neurol 1984; 15(suppl):S192–S202PubMedCrossRefGoogle Scholar
  5. 5.
    Jones RM, Cramer S, Sargent T, Budinger TF. Brain protein synthesis rates measured in vivo using methionine and leucine. J Nucl Med 1985; 26: 830.Google Scholar
  6. 6.
    Lundqvist H, Stålnacke C-G, Långström B, Jones B. Labeled metabolites in plasma after intravenous administration of [11CH3]-L-methionine. In: The metabolism of the human brain studied with positron emission tomography (Greitz T, Ingvar DH, Widén L eds), New York, Raven Press, 1985: 233–240.Google Scholar
  7. 7.
    Buonomo C, Mills P, Hilton J, Anderson JH, Wong DF, Dannals RF. Labelled plasma metabolites of L-methyl-hydrogen-3-methionine and L-methyl-carbonl4-methionine in the dog. Am J Physiol Imag 1988; 3: 178–181.Google Scholar
  8. 8.
    Keen RE, Barrio JR, Huang S-C, Hawkins RA, Phelps ME. In vivo cerebral protein synthesis rates with leucyl-transfer RNA used as a precursor pool: determination of biochemical parameters to structure tracer kinetic models for positron emission tomography. J Cereb Blood Flow Metab 1989; 9: 429–445PubMedCrossRefGoogle Scholar
  9. 9.
    Ishiwata K, Vaalburg W, Elsinga PH, Paans AMJ, Woldring MG. Comparison of L-[11C]methionine and L-methyl-[11C]methionine for measuring in vivo protein synthesis rates with PET. J Nucl Med 1988; 29: 1419–1427.PubMedGoogle Scholar
  10. 10.
    Ishiwata K, Hatazawa J, Kubota K, et al. Metabolic fate of L-[methyl-11C]methionine in human plasma. Eur J Nucl Med 1989; 15: 665–669.PubMedCrossRefGoogle Scholar
  11. 11.
    Ishiwata K, Kameyama M, Hatazawa J, Kubota K, Ido T. Measurement of L-[methyl-11C]methionine in human plasma. Appl Radiat Isot 1991; 42: 77–79.CrossRefGoogle Scholar
  12. 12.
    Smith CB, Deibler GE, Eng N, Schmidt K, Sokoloff L. Measurement of local cerebral protein synthesis in vivo: influence of recycling of amino acids derived from protein degradation. Proc Natl Acad Sci USA 1988; 85: 9341–9345.PubMedCrossRefGoogle Scholar
  13. 13.
    Hargreaves-Wall KM, Buciak JL, Pardridge WM. Measurement of free intracellular and transfer RNA amino acid specific activity and protein synthesis in rat brain in vivo. J Cereb Blood Flow Metab 1990; 10: 162–169.PubMedCrossRefGoogle Scholar
  14. 14.
    Comar D, Saudubray JM, Duthilleul A, et al. Brain uptake of 11C-methionine in phenylcetonuria. Eur J Pediatr 1981; 136: 13–19.PubMedCrossRefGoogle Scholar
  15. 15.
    Bustany P, Henry JF, Soussaline F, Comar D. Brain protein synthesis in normal and demented patiens-a study by positron emission tomography with 11C-L-methionine In: Functional Radionuclide Imaging of the brain (Magistretti PL, ed), New York, Raven Press, 1983: 319–326.Google Scholar
  16. 16.
    Bustany P, Henry JF, de Rotrou J, et al. Correlation between clinical state and positron emission tomography measurement of local brain protein synthesis in Alzheimer’s dementia, Parkinson’s disease schizophrenia, and gliomas. In: Positron emission tomography (Greitz T, Ingvar DH, Widén L, eds), New York, Raven Press, 1985: 241–249.Google Scholar
  17. 17.
    Bergström M, Ericson K, Hagenfeldt L, et al. PET study of methionine accumulation in glioma and normal brain tissue: competition with branched chain amino acids. JComput Assist Tomogr 1987; 11: 208–213.Google Scholar
  18. 18.
    O’Tuama LA, Phillips PC, Smith QR, et al. L-Methionine uptake by human cerebral cortex: maturation from infancy to old age. J Nucl Med 1991; 32: 16–22.PubMedGoogle Scholar
  19. 19.
    Bergström M, Lundqvist H, Ericson K, et al. Comparison of the accumulation kinetics of L-[methy111C]-methionine and D-[methyl11C]-methionine in brain tumors studied with positron emission tomography. Acta Radiol 1987; 28: 225–229.PubMedCrossRefGoogle Scholar
  20. 20.
    Mosskin M, von Holst H, Bergström M, et al. Positron emission tomography with 11Cmethionine and computed tomography of intracranial tumors compared with histopathologic examination of multiple biopsies. Acta Radiol 1987; 28: 673–681.PubMedCrossRefGoogle Scholar
  21. 21.
    Hatazawa J, Ishiwata K, Itoh M, et al. Quantitative evolution of L-[methyl-C11]methionine uptake in tumor using positron emission tomography. J Nucl Med 1989; 30: 1809–1813.PubMedGoogle Scholar
  22. 22.
    Mineura K, Sasajima T, Kowada M, Shishido F, Uemura K. Determination of tumor extent detected by (11C-methyl)-1-methionine positron emission tomography in gliomas. J Cereb Blood Flow Metab 1991; 11 (Suppl 2): S596.Google Scholar
  23. 23.
    Leskinen-Kallio S, Ruotsalainen U, Nagren K, Teräs M, Joensuu H. Uptake of carbon11-methionine and fluorodeoxyglucose in non-Hodgkin’s lymphoma: a PET study. JNucl Med 1991; 32: 1211–1218.PubMedGoogle Scholar
  24. 23.
    Gati I, Bergström M, Muhr C, Langström B, Carlsson J. Application of (methyl-11C). methionine in the multicellular spheroid system. J Nucl Med 1991; 32: 2258–2265.PubMedGoogle Scholar
  25. 25.
    Yoshimine T, Hayakawa T, Kato A, et al. Autoradiographic study of regional protein synthesis in focal ischemia with TCA wash and image subtraction techniques. J Cereb Blood Flow Metab 1987; 7: 387–393.PubMedCrossRefGoogle Scholar
  26. 26.
    Patlak CS, Pettigrew KD. A method to obtain infusion schedules for prescribed blood concentration time courses. J Appl Physiol 1976; 40: 458–463.PubMedGoogle Scholar
  27. 27.
    Planas AM, Prenant C, Mazoyer BM, Comar D, DiGiamberardino L. Regional cerebral L-[14 C-methyl] methionine incorporation into proteins: evidence for methionine recycling in the rat brain. J Cereb Blood Flow Metab 1992: (in press)Google Scholar
  28. 28.
    Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the folin phenol reagent. J Biol Chem 1951; 193: 265–275.PubMedGoogle Scholar
  29. 29.
    Laemmi UK. Cleavage of structural protein during the assembly of the head of the bacteriophage T4. Nature 1970; 227: 680–685.CrossRefGoogle Scholar
  30. 30.
    Shahbazian FM, Jacobs M, Lajtha A. Amino acid incorporation in relation to molecular weight of proteins in young and adult brain. Neurochem Res 1986; 11: 647–660.PubMedCrossRefGoogle Scholar
  31. 31.
    Seta K, Sansur M, Lajtha A. The rate of incorporation of amino acids into brain proteins during infusion in the rat. Biochim Biophys Acta 1973; 294: 472–480PubMedCrossRefGoogle Scholar
  32. 32.
    Morgan HE, Earl DCN, Broadus A, Wolpert EB, Giger KE, Jefferson LS. Regulation of protein synthesis in heart muscle. I. Effect of amino acid levels on protein synthesis. J Biol Chem 1971; 246: 2152–2162.PubMedGoogle Scholar
  33. 33.
    Schreiber SS, Oratz M, Evans C, Reff F, Klein I, Rothschild MA. Cardiac protein degradation in acute overload in vitro: reutilization of amino acids. Am J Physiol 1973; 224: 338–345.PubMedGoogle Scholar
  34. 34.
    McKee EE, Cheung JY, Rannels DE, Morgan HE. Mesurement of the rate of protein synthesis and compartmentation of heart phenylalanine. J Biol Chem 1978; 25: 1030 1040.Google Scholar
  35. 35.
    Everett AW, Prior G, Zak R. Equilibration of leucine between the plasma compartment and leucyl-tRNA in the heart, and turnover of cardiac myosin heavy chain. Biochem J 1981; 194: 365–368.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 1993

Authors and Affiliations

  • A. M. Planas
  • C. Prenant
  • B. M. Mazoyer
  • S. Chadan
  • D. Comar
  • L. Digiamberardino

There are no affiliations available

Personalised recommendations