Abstract
1. Phenethylamines were extracted from brain and liver of rats with phenylketonuria-like characteristics produced in vivo by inhibition of phenylalanine hydroxylase (EC 1.14.3.1) with p-chlorophenylalanine, with or without phenylalanine administration. To protect amines against oxidation by monoamine oxidase, pargyline was also administered. 2. β-Phenethylamine was the major compound found in brain and liver. β-Phenethanolamine and octopamine were also present, in lesser amounts, and the concentrations of these three amines paralleled blood phenylalanine concentrations. By comparison, tissues from control animals had only very low concentrations of these amines. 3. Small amounts of normetadrenaline, m-tyramine and 3-methoxytyramine were also found. 4. The inhibitors used, p-chlorophenylalanine and pargyline, gave rise to p-chlorophenethylamine and benzylamine respectively, the first via decarboxylation, the second probably by breakdown during extraction. 5. Distribution of phenethylamines in different brain regions and in subcellular fractions of rat brain cells was also investigated. The content of phenethylamine was highest in the striatum. 6. These findings are discussed in the light of changes occurring in human patients with uncontrolled phenylketonuria.
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- Abdel-Latif A. A. A simple method for isolation of nerve-ending particles from rat brain. Biochim Biophys Acta. 1966 Jun 29;121(2):403–406. doi: 10.1016/0304-4165(66)90129-2. [DOI] [PubMed] [Google Scholar]
- Autilio L. A., Appel S. H., Pettis P., Gambetti P. L. Biochemical studies of synapses in vitro. I. Protein synthesis. Biochemistry. 1968 Jul;7(7):2615–2622. doi: 10.1021/bi00847a025. [DOI] [PubMed] [Google Scholar]
- Boulton A. A., Milward L. Separation, detection and quantitative analysis of urinary beta-phenylethylamine. J Chromatogr. 1971 May 6;57(2):287–296. doi: 10.1016/0021-9673(71)80042-0. [DOI] [PubMed] [Google Scholar]
- Edwards D. J., Blau K. Analysis of phenylethylamines in biological tissues by gas-liquid chromatography with electron-capture detection. Anal Biochem. 1972 Feb;45(2):387–402. doi: 10.1016/0003-2697(72)90201-1. [DOI] [PubMed] [Google Scholar]
- Edwards D. J., Blau K. Aromatic acids derived from phenylalanine in the tissues of rats with experimentally induced phenylketonuria-like characteristics. Biochem J. 1972 Nov;130(2):495–503. doi: 10.1042/bj1300495. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Edwards D. J., Blau K. The in vivo formation of p-chloro- -phenylethylamine in young rats injected with p-chlorophenylalanine. J Neurochem. 1972 Jul;19(7):1829–1832. doi: 10.1111/j.1471-4159.1972.tb06232.x. [DOI] [PubMed] [Google Scholar]
- Fischer E., Heller B., Miró A. H. Beta-phenylethylamine in human urine. Arzneimittelforschung. 1968 Nov;18(11):1486–1486. [PubMed] [Google Scholar]
- Fuxe K., Grobecker H., Jonsson J. The effect of beta-phenylethylamine on central and peripheral monoamine-containing neurons. Eur J Pharmacol. 1967 Dec;2(3):202–207. doi: 10.1016/0014-2999(67)90088-x. [DOI] [PubMed] [Google Scholar]
- Glowinski J., Iversen L. L. Regional studies of catecholamines in the rat brain. I. The disposition of [3H]norepinephrine, [3H]dopamine and [3H]dopa in various regions of the brain. J Neurochem. 1966 Aug;13(8):655–669. doi: 10.1111/j.1471-4159.1966.tb09873.x. [DOI] [PubMed] [Google Scholar]
- Kurtz D. J., Levy H., Kanfer J. N. Cerebral lipids and amino acids in the vitamin B 6 -deficient suckling rat. J Nutr. 1972 Feb;102(2):291–298. doi: 10.1093/jn/102.2.291. [DOI] [PubMed] [Google Scholar]
- LOO Y. H., RITMAN P. NEW METABOLITES OF PHENYLALANINE. Nature. 1964 Sep 19;203:1237–1239. doi: 10.1038/2031237a0. [DOI] [PubMed] [Google Scholar]
- Loo Y. H., Ritman P. Phenylketonuria and vitamin B6 function. Nature. 1967 Mar 4;213(5079):914–916. doi: 10.1038/213914a0. [DOI] [PubMed] [Google Scholar]
- MCCAMAN R. E., MCCAMAN M. W., HUNT J. M., SMITH M. S. MICRODETERMINATION OF MONOAMINE OXIDASE AND 5-HYDROXYTRYPTOPHAN DECARBOXYLASE ACTIVITIES IN NERVOUS TISSUES. J Neurochem. 1965 Jan;12:15–23. doi: 10.1111/j.1471-4159.1965.tb10246.x. [DOI] [PubMed] [Google Scholar]
- Maas J. W. A kinetic model for the study of the disposition of circulating norepinephrine. J Pharmacol Exp Ther. 1970 Sep;174(3):369–378. [PubMed] [Google Scholar]
- NADLER H. L., HSIA D. Y. Epinephrine metabolism in phenylketonuria. Proc Soc Exp Biol Med. 1961 Aug-Sep;107:721–723. doi: 10.3181/00379727-107-26734. [DOI] [PubMed] [Google Scholar]
- NAKAJIMA T., KAKIMOTO Y., SANO I. FORMATION OF BETA-PHENYLETHYLAMINE IN MAMMALIAN TISSUE AND ITS EFFECT ON MOTOR ACTIVITY IN THE MOUSE. J Pharmacol Exp Ther. 1964 Mar;143:319–325. [PubMed] [Google Scholar]
- Neff N. H., Ngai S. H., Wang C. T., Costa E. Calculation of the rate of catecholamine synthesis from the rate of conversion of tyrosine-14C to catecholamines. Effect of adrenal demedullation on synthesis rates. Mol Pharmacol. 1969 Jan;5(1):90–99. [PubMed] [Google Scholar]
- OATES J. A., NIRENBERG P. Z., JEPSON J. B., SJOERDSMA A., UDENFRIEND S. Conversion of phenylalanine to phenethylamine in patients with phenylketonuria. Proc Soc Exp Biol Med. 1963 Apr;112:1078–1081. doi: 10.3181/00379727-112-28256. [DOI] [PubMed] [Google Scholar]
- PARE C. M., SANDLER M., STACEY R. S. 5-Hydroxytryptamine deficiency in phenylketonuria. Lancet. 1957 Mar 16;272(6968):551–553. doi: 10.1016/s0140-6736(57)90920-0. [DOI] [PubMed] [Google Scholar]
- PERRY T. L. Urinary excretion of amines in phenylketonuria and mongolism. Science. 1962 Jun 8;136(3519):879–880. doi: 10.1126/science.136.3519.879. [DOI] [PubMed] [Google Scholar]
- PORTER C. C., TOTARO J. A., LEIBY C. M. Some biochemical effects of alpha-methyl-3,4-dihydroxyphenylalanine and related compounds in mice. J Pharmacol Exp Ther. 1961 Nov;134:139–145. [PubMed] [Google Scholar]
- Parke D. V., Williams R. T. Studies in detoxication. 81. The metabolism of halogenobenzenes: (a) Penta- and hexa-chlorobenzenes. (b) Further observations on 1:3:5-trichlorobenzene. Biochem J. 1960 Jan;74(1):5–9. doi: 10.1042/bj0740005. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Persson T., Waldeck B. Some problems encountered in attempting to estimate catecholamine turnover using lbbelled tyrosine. J Pharm Pharmacol. 1970 Jul;22(7):473–478. doi: 10.1111/j.2042-7158.1970.tb10549.x. [DOI] [PubMed] [Google Scholar]
- Silberberg D. H. Phenylketonuria metabolites in cerebellum culture morphology. Arch Neurol. 1967 Nov;17(5):524–529. doi: 10.1001/archneur.1967.00470290078010. [DOI] [PubMed] [Google Scholar]
- Whittaker V. P. The application of subcellular fractionation techniques to the study of brain function. Prog Biophys Mol Biol. 1965;15:39–96. doi: 10.1016/0079-6107(65)90004-0. [DOI] [PubMed] [Google Scholar]