Original Article
A review of chemical issues in 1H NMR spectroscopy: N-acetyl-l-aspartate, creatine and choline
Bruce L. Miller,
Bruce L. Miller
UCLA School of Medicine, Harbor-UCLA Medical Center, Bldg B-4 1000 W. Carson Street, Torrance, CA 90509, USA
Search for more papers by this authorBruce L. Miller,
Bruce L. Miller
UCLA School of Medicine, Harbor-UCLA Medical Center, Bldg B-4 1000 W. Carson Street, Torrance, CA 90509, USA
Search for more papers by this authorAbstract
The structure and function of the chemicals contributing to the three main peaks seen with 1H NMR spectroscopy, N-acetyl-L-aspartate (NAA), creatine/phosphocreatine (Cr), and choline-containing compounds (Cho) is reviewed and the changes seen with these compounds in various disease states are briefly outlined. NAA is present within neurons although its biological function is largely unknown. NAA is elevated in several degenerative neurological conditions including amyotrophic lateral sclerosis and canavan disease, and in high concentrations it may behave like a neurotoxin. The creatine peak seen with 1H NMR spectroscopy consists of creatine and phosphocreatine which serve as a reserve for high-energy phosphates in the cytosol of muscle and neurons. They also buffer cellular ATP/ADP. The Cho peak seen with 1H NMR consists of a complex mixture of Cho-containing compounds. Cho is a precursor for the neurotransmitter acetylcholine and for the membrane constituent phosphatidylcholine. Future studies of changes seen in the Cho peak with stroke, degenerative dementia, drug intake, and infectious and neoplastic brain masses will be of great interest.
References
- 1 Remy, C., Von Kienlin, M., Lotito, S., Francois, A., Benabid, A. L. and Decorps, M., In vivo 1H NMR spectroscopy of an intracerebral glioma in the rat. Magn. Reson. Med. 9, 395–401 (1989).
- 2 Segebarth, C. M., Balleriaux, D. F., Arnold, D. L., Luyten, P. R. and den Hollander, J. A., MR image-guided P-31MR spectroscopy in the evaluation of brain tumor treatment. Radiology 165, 215–219 (1987).
- 3 Bruhn, H., Frahm, J., Gyngell, M. L., Merboldt, K. D., Hancicke, W., Sauter, R. and Hamburger, C., Noninvasive differentiation of tumors with use of localized 1H NMR spectroscopy In vivo: Initial experience in patients with cerebral tumors. Radiology 172, 541–548 (1989).
- 4 Segebarth, C. M., Baleriaux, D. F., Luyten, P. R. and den Hollander, J. A., Detection of metabolic heterogeneity of human intracranial tumors In vivo by 1H NMR spectroscopy imaging. Magn. Reson. Med. 13, 62–76 (1990).
- 5 Miller, B. L., McBride, D., Riedy, G., Caron, M., Lipcamon, J. and O'Brien, D., Changes in brain choline in tumors versus infection with 1H NMR spectroscopy. Bull. Clin. Neurosci., (in press).
- 6 Crockard, H. A., Gadian, D. G., Frackowiak, R. S. J., Proctor, E., Allen, K., Williams, S. R. and Russell, R. W. R., Acute cerebral ischaemia: concurrent changes in cerebral blood flow, energy metabolites, pH and lactate measured with hydrogen clearance and 31P and 1H nuclear magnetic resonance spectroscopy. II. Changes during ischaemia. J. Cereb. Blood Flow. Metab. 7, 394–402 (1987).
- 7 Behar, K. L., Detection of cerebral lactate In vivo during acute hypoxemia by H1 NMR at relatively low field strength (1.9 T). Proc. NatlAcad. Sci. USA 81, 2517–2519 (1984).
- 8 Bruhn, H., Frahm, J., Gyngell, M., Merboldt, K. D., Hanicke, W. and Sauter, R., Cerebral metabolism in man after acute stroke: new observations using localized proton NMR spectroscopy. Magn. Reson. Med. 9, 126–131 (1989).
- 9 Kreis, R., Farrow, N. and Ross, B. D., Diagnosis of hepatic encephalopathy by cerebral proton magnetic resonance spectroscopy. Lancet 336, 635–636 (1990).
- 10 Pettegrew, J. W., in vitro and In vivo NMR spectroscopy in Alzheimer disease. Bull. Clin. Neurosci. 53, 105–119 (1988).
- 11 Brown, G. G., Levine, S. R., Gorell, J. M., Pettegrew, J. W., Gdowski, J. W., Bueri, J. A., Helpern, J. A. and Welch, M. W., In vivo 31P NMR profiles of Alzheimer's disease and multiple subcortical infarct dementia. Neurology 39, 1423–1426 (1989).
- 12 Pettegrew, J. W., Molecular insights into Alzheimer's disease. Ann. N.Y. Acad. Sci. 568, 5–28 (1989).
- 13 Petroff, O. A. C., Spencer, D. D., Alger, J. R. and Prichard, J. W., High-field proton magnetic resonance spectroscopy of human cerebrum obtained during surgery for epilepsy. Neurology 39, 1187–1190 (1989).
- 14 Tallan, H. H., Studies on the distribution of N-acetyl-L-aspartic acid in brain. J. Biol. Chem. 224, 41–45 (1956).
- 15 Koller, K. J., Zaczek, R. and Coyle, J., N acetyl-aspartylglutamate: regional levels in rat brain and the effects of brain lesions as determined by a new HPLC method. J. Neurochem. 43, 1136–1142 (1984).
- 16 Passani, L., Tsai, G., Slusher, B. S., Simmons, M. and Coyle, J. T., Immunocytochemical co-localization of N-acetyl-aspartate and N-acetylaspartylglutamate in monkey. Soc. Neurosci. Abst. 16, 1190 (1990).
- 17 Simmons, M. L., Frondoza, C. and Coyle, J. T., Monoclonal antibodies to N-acetyl-aspartate. Soc. Neurosci. Abst. 16, 1190 (1990).
- 18 Rothstein, J. D., Tsai, G., Kuncl, R. W., Clawson, L., Cornblath, D. R., Drachman, D. B., Pestronk, A., Stauch, B. L. and Coyle, J. T., Abnormal excitatory amino acid metabolism in amyotrophic lateral sclerosis. Ann. Neurol. 28, 18–25 (1990).
- 19 Choi, D. W., Glutamate neurotoxicity and diseases of the nervous system. Neuron 1, 623–634 (1988).
- 20 Robinson, M. B. and Coyle, J. T., Glutamate and related acid excitatory neurotransmitters: from basic science to clinical application. FASEB. J. 1, 446–455 (1987).
- 21 Matalon, R., Michals, K., Sevesta, D., Deanching, M., Gashkoff, P. and Casanova, J., Asparto-acylase deficiency and N-acetylaspartic aciduria in patients with canavan disease. Am. J. Med. Genet. 20, 463–471 (1988).
- 22 Arnold, D. L., Matthews, P. M., Francis, G. and Antel, J., Proton magnetic resonance spectroscopy of human brain In vivo in the evaluation of multiple sclerosis: assessment of the load of disease. Magn. Reson. Med. 14, 154–159 (1990).
- 23 Rodwell, V. W., Conversion of amino acids to specialized products, in Harper's Review of Biochemistry, ed. by D. W. Martin, P. A. Mayes and V. W. Rodwell, 18th edn., pp. 299–305. Lange Medical Publications, Los Altos, California (1981).
- 24 Walker, J. B., Creatine: biosynthesis, regulation and function, in Advances in Enzymology and Related Areas of Molecular Biology ed. by A. Meister, Vol. 50, pp. 144–242. John Wiley and Sons, New York (1980).
- 25 Wurtman, J. J., Sources of choline and lecithin in the diet. Nutri. Brain 5, 73–81 (1979).
- 26 Freeman, J. J. and Jenden, D. J., The source of choline for acetylcholine synthesis in brain. Life Sciences 19, 949–962 (1976).
- 27 Pelech, S. L. and Vance, D. E., Regulation of phosphatidylcholine biosynthesis. Biochim. Biophys. Acta, 779, 217–251 (1984).
- 28 Jenden, D. J., Roch, M. and Booth, R., Simultaneous measurement of endogenous and deuterium labelled tracer variants of choline and acetylcholine in subpicomole quantities by gas chromatography/mass spectrometry. Anal. Biochem. 55, 438–448 (1973).
- 29 Jope, R. S. and Jenden, D. J., Choline and phospholipid metabolism and synthesis of acetylcholine in rat brain. J. Neurosci. Res. 4, 69–82 (1979).
- 30 Thompson, G. A., Phospholipid metabolism in animal tissues, in Form and Function of Phospholipids, ed. by G. B. Ansell, J. N. Jawthorne and R. M. C. Dawson, pp. 67–96. Elsevier, Amsterdam (1973).
- 31 Boesch, C., Gruetter, R., Martin, E., Duc, G. and Wüthrich, K., Variations in the In vivo P-31 MR spectra of the developing human brain during postnatal life. Radiology 172, 197–199 (1989).
- 32
Barany, M.,
Langer, B. G.,
Glick, R. P.,
Venkatasubramanian, N.,
Wilbur, A. C. and
Spigos, D. G.,
In vivo H-1 spectroscopy in humans at 1.5 T.
Radiology
167,
39–844
(1988).
10.1148/radiology.167.3.3283842 Google Scholar
- 33 Tungaal, B., Hofmann, K. and Stoffel, W., In vivo 13C nuclear magnetic resonance investigations of choline metabolism in rabbit brain. Magn. Reson. Med. 13, 90–102 (1990).
- 34 Riedy, G. and Miller, B. L., Phosphatidylcholine contributes to the choline peak in 1H NMR spectroscopy. Bull. Clin. Neurosci. (in press).
- 35 Scremin, O. U. and Jenden, D. J., Focal ischemia enhances choline output and decreases acetylcholine output from rat cerebral cortex. Stroke 20, 92–95 (1989).
- 36 Davies, P. and Maloney, A. J. F., Selective loss of central cholinergic neurons in Alzheimer's disease. Lancet 2, 1402 (1976).
- 37 Vinters, H., Miller, B. L. and Pardridge, W., Brain amyloid and Alzheimer disease. Ann. Int. Med. 109, 41–54 (1988).
- 38 Coyle, J. T., Price, D. L. and DeLong, M. R., Alzheimer's disease: a disorder or cortical cholinergic innervation. Science 219, 1184–1190 (1983).
- 39 Drachman, D. A., Memory and cognitive functions in man: does the cholinergic system have a specific role? Neurology 27, 783–790 (1977).
- 40 Blusztajn, J. K. and Wurtman, R. Choline and cholinergic neurons. Science 221, 614–620 (1983).
- 41 Martin, K., Concentrative accumulation of choline by human erythrocytes. J. Gen. Physiol. 51, 497–516 (1968).
- 42 Miller, B. L., Lin, K. L., Djenderedjian, A., Tang, C., Hill, E., Fu, P., Nuccio, C. and Jenden, D. J., Changes in red blood cell choline and choline-bound lipids with oral lithium. Experientia 46, 454–456 (1989).
- 43 Kim, D. and Clapman, D. E., Potassium channels in cardiac cells activated by arachidonic acid and phospholipids. Science 244, 174–176 (1990).
- 44 Lou, H. O. Christensen, Clausen, J. and Bierring, F., Phospholipids and glycolipids of tumors in the central nervous system. J. Neurochem. 12, 619 (1965).
- 45 Daly, P. F., Zugmaier, G., Sandler, D., Carpen, M., Myers, C. E. and Cohen, J. S., Regulation of the cytidine phospholipid pathways in human cancer cells and effects of 1-β-D-arabinofuranosylcytosine: a noninvasive 31P nuclear magnetic resonance study. Cancer Res. 50, 554–557 (1990).
- 46 Podo, F., Carpinelli, G., Di Vito, M., Giannini, M., Proietti, E., Fiers, W., Gresser, I. and Belardelli, F., Nuclear magnetic resonance analysis of tumor necrosis factor-induced alterations of phospholipid metabolites and pH in Friend leukemia cell tumors and fibrosarcomas in mice. Cancer Res. 24, 6481–6489 (1987).
- 47 Belardelli, F., Proietti, E., Ciolli, V., Sestili, P., Carpinelli, G., Di Vito, M., Ferretti, A., Woodrow, D., Boraschi, D. and Podo, F., Lnterleukin-1 B induces tumor necrosis and early morphologic and metabolic changes in transplantable mouse tumors. Similarities with the anti-tumor effects of tumor necrosis factor alpha or beta. Int. J. Cancer 44, 116–123 (1989).
