Summary
Many pathways of essential neutral amino acid metabolism in the CNS are influenced by precursor availability. Since the delivery of circulating amino acids to brain cells is primarily controlled by the rate of amino acid transport through the blood-brain barrier (BBB), pathways of brain amino acid metabolism are ultimately influenced by the activity (Km, Vmax) of the BBB neutral amino acid transport system. The Km of BBB transport is in the 0.1–0.6 mM range, which approximates the physiologic plasma levels and forms the basis of the unusual sensitivity of the brain to competition effects on neutral amino acid transport. Unlike the brain, the Km of amino acid transport into other organs is in the 1–10 mM range or greater, which frees these tissues from competition effects in the physiologic range of plasma amino acids. Tryptophan circulates 80–90% bound to albumin; however, the capacity/affinity ratio of the BBB neutral amino acid transport system exceeds the capacity/affinity ratio of albumin binding of tryptophan, which enables the carrier to strip tryptophan off albumin as it traverses the brain capillary. The activity of the BBB neutral amino acid transport system is probably not modulated by insulin, but is influenced by changes in thyroid hormone status; the transport system is also induced in states of hepatic encephalopathy and this induction process is the primary cause of the increased brain tryptophan and serotonin levels in cirrhosis.
Supported by the National Science Foundation (BNS 78-05500).
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References
Adibi, S. A., Mercer, D. W.: Protein digestion in human intestine as reflected in luminal, mucosal and plasma amino acid concentrations after meals. J. Clin. Invest. 52, 1586–1594 (1973).
Ames, A., III, Parks, J. M.: Functional homogeneity of leucine pool in retina cells. J. Neurochem. 27, 1017–1025 (1976).
Baños, G., Daniel, P. M., Moorhouse, S. R., Pratt, O. E.: The influx of amino acids into the brain of the rat in vivo: The essential compared with some non-essential amino acids. Proc. R. Soc. Lond. (Biol.) 183, 59–70 (1973).
Begin, N., Scholefield, P. G.: The uptake of amino acids by mouse pancreas in vitro. II. The specificity of the carrier systems. J. Biol. Chem. 240, 332–338 (1965).
Betz, A. L., Gilboe, D. D.: Effect of pentobarbital on amino acid and urea flux in the isolated dog brain. Am. J. Physiol. 224, 580–587 (1973).
Birkmayer, W., Danielczyk, W., Neumayer, E., Riederer, P.: L-Dopa level in plasma, primary condition for the kinetic effect. J. Neural Transm. 34, 133–143 (1973).
Chan, Y. Z., Huang, K. C.: Microperfusion studies on renal tubular transport of tryptophan derivatives in rats. Am. J. Physiol. 221, 575–579 (1971).
Chaplin, E. R., Goldberg, A. L., Diamond, I.: Leucine oxidation in brain slices and nerve endings. J. Neurochem. 26, 701–707 (1976).
Chung-Hwang, E., Khurana, H., Fisher, H.: The effect of dietary histidine level on the carnosine concentration of rat olfactory bulbs. J. Neurochem. 26, 1087–1091 (1976).
Coyle, J. T.: Tyrosine hydroxylase in rat brain-cof actor requirements, regional and subcellular distribution. Biochem. Pharmacol. 21, 1935 to 1942 (1972).
Cummings, M. G., Soeters, P. B., James, J. H., Keane, J. M., Fischer, J. E.: Regional brain indoleamine metabolism following chronic portacaval anastomosis in the rat. J. Neurochem. 27, 501–509 (1976).
Curzon, G., Kantamaneni, B. D., Fernando, J. C, Woods, M. S., Cavanagh, J. B.: Effects of chronic porto-caval anastomosis on brain tryptophan, tyrosine and 5-hydroxytryptamine. J. Neurochem. 24, 1065–1070 (1975).
Daniel, P. M., Love, E. R., Pratt, O. E.: Hypothyroidism and amino acid entry into brain and muscle. Lancet 2, 872 (1975).
Daniel, P. M., Moorhouse, S. R., Pratt, O. E.: Do changes in blood levels of other aromatic amino acids influence levodopa therapy? The Lancet 1, 95 (1976).
De Montis, M. G., Olianas, M. C., Haber, B., Taglamonte, A.: Increase in large neutral amino acid transport into brain by insulin. J. Neurochem. 30, 121–124 (1978).
Felig, P., Wahren, J., Ahlborg, G.: Uptake of individual amino acids by the human brain. Proc. Soc. Exp. Biol. Med. 142, 230–231 (1973).
Friedman, P. A., Kappelman, A. H., Kaufman, S.: Partial purification and characterization of tryptophan hydroxylase from rabbit hindbrain. J. Biol. Chem. 247, 4165–4173 (1972).
Guroff, G., Udenfriend, S.: Studies on aromatic amino acid uptake by rat brain in vivo. J. Biol. Chem. 237, 803–806 (1962).
Hertz, M. M., Bolwig, T. G.: Blood-brain barrier studies in the rat: An indicator dilution technique with tracer sodium as an internal standard for estimation of extracerebral contamination. Brain Res. 107, 333–343 (1976).
Jacoby, J. H., Mueller, G., Wurtman, R. J.: Thyroid state and brain monoamine metabolism. Endocrinology 97, 1332–1335 (1975).
James, J. H., Escourrou, J., Fischer, J. E.: Blood brain neutral amino acid transport activity is increased after portacaval anastomosis. Science 200, 1395–1397 (1978).
Larsen, P. R., Ross, J. E., Tapley, D. F.: Transport of neutral, dibasic and N-methyl substituted amino acids by rat intestine. Biochim. Biophys. Acta 88, 570–577 (1964).
Le Cam, A., Freychet, P.: Neutral amino acid transport. Characterization of the A and L system in isolated rat hepatocytes. J. Biol. Chem. 252, 148–156 (1977).
Lingard, J., Rumrich, G., Young, J. A.: Kinetics of L-histidine transport in the proximal convolution of rat nephron studied using the stationary microperfusion technique. Pfluegers Arch. 342, 13–28 (1973).
Madras, B. K., Cohen, E. L., Messing, R., Munro, H. N., Wurtman, R. J.: Revelance of free tryptophan in serum to tissue tryptophan concentrations. Metabolism 23, 1107–1116 (1974).
Matthyse, S., Baldessarini, R. J., Vogt, M.: Methionine adenosyltransferase: A double-isotope derivative, enzymatic assay. Anal. Biochem. 48, 410 to 421 (1972).
McMenamy, R. H., Lund, C. C, Van Marche, J., Oncley, J. L.: The binding of L-tryptophan in human plasma at 37 °C. Arch. Biochem. Biophys. 93, 135–139 (1961).
Neff, N. H., Spano, P. F., Groppetti, A., Wang, C. T., Costa, E.: A simple procedure for calculating the synthesis rate of norepinephrine, dopamine, and serotonin in rat brain. J. Pharmacol. Exp. Ther. 176, 701–710 (1971).
Oldendorf, W. H.: Measurement of brain uptake of radiolabeled substances using a tritiated water internal standard. Brain. Res. 24, 372–376 (1970).
Pardridge, W. M., Oldendorf, W. H.: Kinetic analysis of blood-brain barrier transport of amino acids. Biochim. Biophys. Acta 401, 128–136 (1975).
Pardridge, W. M., Oldendorf, W. H.: Transport of metabolic substrates through the blood-brain barrier. J. Neurochem. 28, 5–12 (1977).
Pardridge, W. M.: Kinetics of competitive inhibition of neutral amino acid transport across the blood-brain barrier. J. Neurochem. 28, 103–108 (1977 a).
Pardridge, W. M.: Regulation of amino acid availability to the brain. In: Nutrition and the Brain, Vol. 1 (Wurtman, R. J., Wurtman, J. J., eds.), pp. 141-204. New York. 1977 b.
Pardridge, W. M.: Unidirectional influx of glutamine and other neutral amino acids in liver of fed and fasted rat in vivo. Am. J. Physiol. 232, E492–E496 (1977 c).
Riggs, T. R.: Hormones and transport across cell membranes. In: Biochemical Actions of Hormones, Vol. 1 (Litwack, G., ed.), pp. 157-208. New York. 1970.
Riggs, T. R., McKirahan, K. J.: Action of insulin on transport of L-alanine in rat diaphragm in vitro. J. Biol. Chem. 248, 6450–6455 (1973).
Ruderman, N. B., Ross, P. S., Berger, M., Goodman, M. N.: Regulation of glucose and ketone-body metabolism in brain of anesthetized rats. Biochem. J. 138, 1–10 (1974).
Schwartz, J. C., Lampart, C, Rose, C.: Histamine formation in rat brain in vivo: Effects of histidine loads. J. Neurochem. 19, 801–810 (1972).
Wade, L. A., Katzman, R.: Synthetic amino acids in the nature of L-Dopa transport at the blood-brain barrier. J. Neurochem. 25, 837–842 (1975).
Winter, C.G., Christensen, H. N.: Migration of amino acids across the membrane of the human erythrocyte. J. Biol. Chem. 239, 872–878 (1964).
Yuwiler, A., Oldendorf, W. H., Geller, E., Braun, L.: Effect of albumin binding and amino acid competition on tryptophan uptake into brain. J. Neurochem. 28, 1015–1023 (1977).
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Pardridge, W.M. (1979). The Role of Blood-Brain Barrier Transport of Tryptophan and Other Neutral Amino Acids in the Regulation of Substrate-Limited Pathways of Brain Amino Acid Metabolism. In: Baumann, P. (eds) Transport Mechanisms of Tryptophan in Blood Cells, Nerve Cells, and at the Blood-Brain Barrier. Journal of Neural Transmission, vol 15. Springer, Vienna. https://doi.org/10.1007/978-3-7091-2243-3_4
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