Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The phenylalanine analogues p-chlorophenylalanine and alpha-methylphenylalanine were used to inhibit phenylalanine hydroxylase in animal models for phenylketonuria. The present report examines the affects of these analogues on the metabolism of neuroblastoma cells. p-Chlorophenylalanine inhibited growth and was toxic to neuroblastoma cells. Although in vivo this analogue increased cell monoribosomes by 42%, it did not significantly affect poly(U)-directed protein synthesis in vitro. P-Chlorophenylalanine did not compete with phenylalanine or tyrosine for aminoacylation of tRNA and was therefore not substituted for those amino acids in nascent polypeptides. The initial cellular uptake of various large neutral amino acids was inhibited by this analogue but did not affect the flux of amino acids already in the cell; this suggested that an alteration of the cell's amino acid pools was not responsible for the cytotoxicity of the analogues. In contrast with p-chlorophenylalanine, alpha-methylphenylalanine did not exert these direct toxic effects because the administration of alpha-methylphenylalanine in vivo did not affect brain polyribosomes and a comparable concentration of this analogue was neither growth inhibitory nor cytotoxic to neuroblastoma cells in culture. The suitability of each analogue as an inhibitor of phenylalanine hydroxylase in animal models for phenylketonuria is discussed.
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PMID:Effects of p-chlorophenylalanine and alpha-methylphenylalanine on amino acid uptake and protein synthesis in mouse neuroblastoma cells. 15 35

A selection procedure was devised for neurons and related cells that depends upon the ability of the cells to synthesize certain amine neurotransmitters. The rationale for selection is that tyrosine is an essential amino acid for most mammalian cells and that three enzymes from mammalian sources can catalyze the synthesis of tyrosine: phenylalanine hydroxylase (EC 1.14.16.1), tyrosine hydroxylase (EC 1.14.16.2), and tryptophan hydroxylase (EC 1.14.16.4). Tyrosine hydroxylase is found predominantly in adrenergic neurons and related cells that synthesize dopamine, norepinephrine, and epinephrine, and tryptophan hydroxylase in cells synthesizing serotonin or melatonin. Only 1 out of 70,000 uncloned mouse neuroblastoma cells grew well in the absence of tyrosine. Approximately 50% of the cell lines obtained by selection had tyrosine hydroxylase activity. This selection procedure thus provides a simple means of obtaining cell lines of neural origin on the basis of their ability to synthesize putative transmitters.
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PMID:Selection for neuroblastoma cells that synthesize certain transmitters. 415 49