Abstract
Through use of the high-resolution double-focusing mass spectrometer, copper has been identified in various regions of the mouse, rat, guinea pig, rabbit, and human brain. The procedure depends on converting the copper (in ashed tissue) to its chloride salt, followed by derivatization with tetraphenylporphyrin (TPP) to yield a TPP chelate. After chromatographic separation, this chelate is assessed in the mass spectrometer by the integrated-ion-current procedure. Deuterated metal TPP chelates and the rare stable isotope65Cu were used as internal standards. Whole brain values obtained were as follows: mouse, 6.67±0.16 (mean±SEM) μg/g wet weight of tissue; rat, 1.06±0.05; guinea pig, 5.40±0.63; and rabbit, 7.52±0.76. In the rat, the cerebellum contained the highest concentration (1.25 μg/g), and the striatum the lowest (0.70 μg/g). In the human brain, the cortex (gray) and the striatum were relatively the highest copper-containing regions, with the cerebellum (white) being the lowest.
Similar content being viewed by others
References
Pfeiffer, C. C., andIliev, V. 1972. A study of zinc deficiency and copper excess in the schizophrenias. Pages 141–165,in Pfeiffer, C. C. (ed.), International Review of Neurobiology, Supplement 1, Academic Press, New York.
Boggess, R. K., andMartin, R. B. 1975. Copper(II) chelation of dopa, epinephrine, and other catechols. J. Am. Chem. Soc. 97:3076–3081.
Rajan, K. S. 1974. Metal chelates in the storage and transport of neurotransmitter: Interactions of Cu++ with ATP and biogenic amines. J. Neurochem. 22:137–147.
Roberts, G. C. K. 1966. The formation of complexes between 5-hydroxytryptamine, adenosine triphosphate and bivalent cationsin vitro. Biochem. J. 100:30p.
Kwik, W. L., Purdy, E., andStiefel, E. I. 1974. Copper complexes of dopa control of the bonding mode. J. Am. Chem. Soc. 96:1638–1639.
Sigel, H., Becker, K., andMcCormick, D. B. 1967. Ternary complexes in solution. Influence of 2,2′-bipyridyl on the stability of 1:1 complexes of Co++, Ni++, Cu++ and Zn++ with hydrogen phosphate, adenosine 5′-monophosphate, and adenosine 5′-triphosphate. Biochim. Biophys. Acta. 148:655–664.
Sigel, H., andNaumann, C. E. 1976. Ternary complexes in solution. XXIV. Metal ion bridging of stacked purine-indole adducts. The mixed-ligand complexes of adenosine 5′-triphosphate, tryptophan and manganese(II), copper(II), or zinc(II). J. Am. Chem. Soc. 98:730–739.
Sourkes, T. L. 1972. Parkinson's disease and other disorders of the basal ganglia. Pages 565–578,in Albers, R. W., Siegel, G. J., Katzman, R., andAgranoff, B. W. (eds.), Basic Neurochemistry, Little, Brown and Company, Boston.
Pfeiffer, C. C. 1974. Observations on the therapy of the schizophrenia. J. Appl. Nutr. 26:29–36.
Marston, H. R. 1952. Cobalt, copper and molybdenum in nutrition of animals and plants. Physiol. Rev. 32:66–121.
Innes, J. R. M., andShearer, G. D. 1940. “Swayback: A demyelinating disease of lambs with affinities to Schilder's encephalitis in man. J. Comp. Pathol. Ther. 53:1–41.
Carnes, W. H. 1971. Role of copper in connective tissue metabolism. Fed. Proc. 30:995–1000.
Goldstein, M. 1966. Dopamine-β-hydroxylase: A copper enzyme. Pages 443–454,in Peisach, J., Aisen, P., andBlumberg, W. E. (eds.), The Biochemistry of Copper, Academic Press, New York.
Underwood, E. J. 1971.In Trace Elements in Human and Animal Nutrition, Academic Press, New York.
Cumings, J. N. 1948. The copper and iron content of brain and liver in the normal and in hepatolentricular degeneration. Brain 71:410–415.
Holmberg, C. G., andLaurell, C. B. 1951. Oxidase reactions in human plasma caused by ceruloplasmin. Scand. J. Clin. Lab. Invest. 3:103–107.
Angel, C., Leach, B. E., Martens, S., Cohen, M., andHeath, R. G. 1957. Serum oxidation tests in schizophrenic and normal subjects. Arch. Neurol. Psych. 78:500–504.
Chugh, T. D., Dhingra, R. K., Gulati, R. C., andBathla, J. C. 1973. Copper metabolism in schizophrenia. Indian J. Med. Res. 61:1147–1152.
Gubler, C. J., Cartwright, G. E., andWintrobe, M. M. 1950. The anemia of infection. XI. The effect of turpentine and cobalt on the absorption of iron by the rat. J. Biol. Chem. 184:575–578.
Papavasiliou, P. S., Miller, S. T., andCotzias, G. C. 1968. Functional interactions between biogenic amines, 3′, 5′-cyclic AMP and manganese. Nature 220:74–75.
Hadžović, S., Košak, R., andStern, P. 1966. The effect of tremorigenic substances on the copper content of the rat brain. J. Neurochem. 13:1027–1029.
Wong, P. Y., andFritze, K. 1969. Determination by neutron activation of copper, manganese and zinc in the pineal body and other areas of brain tissue. J. Neurochem. 16:1231–1234.
Parr, R. M., andTaylor, D. M. 1964. The concentrations of cobalt, copper, iron and zinc in some normal human tissues as determined by neutron-activation analysis. Biochem. J. 91:424–431.
Sowell, W. L. 1967. Trace Metal Alternations during Endrin Intoxication, University Microfilms, Ann Arbor, Michigan.
Kofod, B. 1970. Iron, copper and zinc in rat brain. Eur. J. Pharmacol. 13:40–45.
Hanig, R. C., andAprison, M. H. 1967. Determination of calcium, copper, iron, magnesium, manganese, potassium, sodium, zinc and chloride concentration in several brain areas. Anal. Biochem. 21:169–177.
Warren, P. J., Earl, C. J., andThompson, R. H. S. 1960. The distribution of copper in human brain. Brain 83:709–717.
Harrison, W. W., Netsky, M. G., andBrown, M. D. 1968. Trace elements in human brain copper, zinc and magnesium. Clin. Chim. Acta 21:55–60.
Backer, E. T. 1969. Chloric acid digestion in the determination of trace metals (Fe, Zn, and Cu) in brain and hair by atomic absorption spectrophotometry. Clin. Chim. Acta 24:233–238.
Dulka, J. J., andRisby, T. H. 1976. Ultratrace metals in some environmental and biological systems. Anal. Chem. 48:640A-653A.
Hui, K. S., Davis, B. A., andBoulton, A. A. 1975. The separation by thin-layer chromatography of trace metals as their tetraphenylporphyrin chelates. J. Chromatogr. 115:581–586.
Davis, B. A., Hui, K. S., Durden, D. A., andBoulton, A. A. 1976. Qualitative and quantitative mass spectrometry of some biologically important trace metals as their tetraphenylporphyrin chelates. Biomed. Mass Spectrom. 3:71–76.
Davis, B. A., Hui, K. S., andBoulton, A. A. The analysis of trace metals as their tetraphenylporphyrin chelates by the mass spectrometric integrated ion current technique.In Frigerio, A., andDesiderio, D. M. (eds.), Advances in Mass Spectrometry in Biochemistry and Medicine, Spectrum Publication Inc., New York (in press).
Glowinski, J., andIversen, L. L. 1966. Regional studies of catecholamines in rat brain. I. The disposition of3H-norepinephrine,3H-dopamine and3H-dopa in various regions of the brain. J. Neurochem. 13:655–669.
Boulton, A. A., andWu, P. H. 1973. Biosynthesis of cerebral phenolic amines. II.In vivo regional formation ofp-tyramine and octopamine from tyrosine and dopamine. Can. J. Biochem. 51:428–435.
Donaldson, J., St-Pierre, T., Minnich, J. L., andBarbeau, A. 1973. Determination of Na+, K+, Mg2+, Cu2+, Zn2+ and Mn2+ in rat brain regions. Can. J. Biochem. 51:87–92.
Kowalski, B. R., Isenhour, T. L., andSievers, R. E. 1969. Ultra-trace mass spectrometric metal analysis using heptafluorodimethyloctanedione chelates. Anal. Chem. 41:998–1003.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Hui, KS., Davis, B.A. & Boulton, A.A. Analysis of copper in brain by the mass-spectrometric integrated-ioncurrent procedure. Neurochem Res 2, 495–506 (1977). https://doi.org/10.1007/BF00966010
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00966010