Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0031511 (pheochromocytoma)
 14,622 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ability of 2-amino-4-hydroxy-7-[dihydroxylpropyl-(L-erythro)-5,6,7,8-tetrahyd ropterin] ("7-tetrahydrobiopterin" or 7-BH4) to substitute for the natural cofactor tetrahydrobiopterin (BH4) has been studied in vitro in the reactions of the three mammalian aromatic amino acid hydroxylases. With rat liver phenylalanine hydroxylase, the apparent Km for 7-BH4 is 160 microM, a value that is approximately 60-fold greater than that for the natural cofactor. In contrast, the hydroxylase reaction is severely inhibited by as little as 1 microM 7-BH4 when assayed in the presence of physiological concentrations of BH4. This inhibition can be overcome either by an increase in the concentration of BH4 or a decrease in the concentration of phenylalanine. With both rat brain tryptophan hydroxylase and rat pheochromocytoma tyrosine hydroxylase, the Km value for 7-BH4 is about one order of magnitude greater than the Km for BH4. Accordingly, 7-BH4 is a poor competitive inhibitor of both tryptophan and tyrosine hydroxylase. Thus, our results suggest that the observed hyperphenylalaninemia in patients who excrete 7-BH4 in their urine may arise directly from the inhibition of phenylalanine hydroxylase by low levels of this pterin. On the other hand, it is less likely that low levels of 7-BH4 would affect the activity of tyrosine or tryptophan hydroxylase in vivo.
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PMID:"7-tetrahydrobiopterin," a naturally occurring analogue of tetrahydrobiopterin, is a cofactor for and a potential inhibitor of the aromatic amino acid hydroxylases. 135 35

The reverse transcription of mRNA of a human pheochromocytoma using an oligonucleotide complementary to rat DOPA decarboxylase (DDC) sequence as a primer, gave rise to a single strand cDNA. This resultant cDNA permitted by PCR amplification the preparation and cloning in PUC 19 of a human DDC probe of 747 base pairs. The choice of primer was dictated by the presence of tryptophan codons in the DOPA decarboxylase sequence which were conserved in different species throughout evolution. The presence of mismatches on the primers was not an obstacle to a specific amplification and the probe sequence was found identical to the human DDC cDNA sequence. This probe, labelled by nick translation detected on Southern blot of human-rodent hybrids, bands on human DNA after EcoRI, BamHI or HindIII digestion. The results with EcoRI were explicit and drove to the conclusion that DDC is located on chromosome 7. Five bands were obtained on human DNA digested with EcoRI, indicating that either numerous introns could interrupt the coding sequence of DDC gene or duplicated sequences could be present in chromosome 7.
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PMID:Preparation of a human DOPA decarboxylase cDNA probe by PCR and its assignment to chromosome 7. 171 Apr 30

Out of carcinogenic heterocyclic amines, which are produced by pyrolysis of tryptophan in food, 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) were found to reduce the activity of enzymes related to catecholamine metabolism in clonal rat pheochromocytoma PC12h cells. By 6 days' culture in the presence of 10 nM to 10 microM Typ-P-1 and -2, these heterocyclic amines were accumulated in the cells, and activity of tyrosine hydroxylase (TH) and aromatic L-aminoacid decarboxylase (AADC) were reduced markedly. Reduction of these enzyme activity was observed with Trp-P-1 and -2 at the concentrations lower than 1 microM, while cell protein and enzyme activity of a non-specific enzyme, beta-galactosidase were reduced only with 10 microM Trp-P-1. These results show that these heterocyclic amines are neurotoxins specific for dopaminergic neurons.
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PMID:Reduction of enzyme activity of tyrosine hydroxylase and aromatic L-aminoacid decarboxylase in clonal pheochromocytoma PC12h cells by carcinogenic heterocyclic amines. 290 12

We have developed a routine capillary gas-chromatographic profiling method for simultaneous quantitative determination of the tert-butyldimethylsilyl derivatives of homovanillic acid, vanilmandelic acid, 3-methoxy-4-hydroxyphenylethylene glycol, and 3,4-dihydroxyphenylacetic acid and the estimation of 5-hydroxyindole-3-acetic acid in urine. The method is useful for diagnosis and followup of patients with functional tumors characterized by increased urinary excretion of metabolites originating from the metabolism of tyrosine and tryptophan--e.g., neuroblastoma, pheochromocytoma, carcinoid, and melanoma. It may also be applicable in pharmacokinetic studies of administered aromatic amino acids (parkinsonism, mental diseases, loading tests) and for diagnosis and followup of patients with inborn errors of metabolism that are characterized by organic aciduria (for instance, tyrosyluria and phenylketonuria).
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PMID:Simultaneous determination of the four major catecholamine metabolites and estimation of a serotonin metabolite in urine by capillary gas chromatography of their tert-butyldimethylsilyl derivatives. 746 Feb 71

The uptake of (6R)-5,6,7,8-tetrahydro-L-biopterin (BH4) was investigated in rat brain synaptosomes, cultured rat pheochromocytoma (PC12) cells, and rat striatum (control and depleted of dopamine neurons) following peripheral administration. A linear, non-saturable, concentration-dependent intracellular accumulation was observed when BH4 was added to either synaptosomes or PC12 cells. The uptake of BH4, in contrast to that of serotonin uptake into synaptosomes or norepinephrine (NE) uptake into PC12 cells, was not dependent on glucose or extracellular sodium. Stimulation of tryptophan hydroxylation in synaptosomes by incubation with 5 microM tryptophan (which increases utilization of BH4 in serotonergic cells) did not alter BH4 uptake. In rats with unilateral 6-hydroxydopamine (6-OHDA) lesions of dopamine neurons, BH4 uptake was the same in control and lesioned striatum following peripheral administration. These results indicate that neurons and PC12 cells do not appear to have a specific membrane carrier for BH4 and that BH4 uptake into cells is due to passive diffusion.
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PMID:Tetrahydrobiopterin uptake into rat brain synaptosomes, cultured PC12 cells, and rat striatum. 788 22

The effects of heterocyclic amines, pyrolysis products of tryptophan, on monoamine metabolism were examined. Among these amines, 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) are potent inhibitors of the enzymes related to amine metabolism. They inhibited type A monoamine oxidase more markedly than type B. After culture of a dopamine cell model, clonal pheochromocytoma PC12h cells, with Trp-P-1 activity of tyrosine hydroxylase was decreased by reduction of its affinity to the biopterin cofactor. Trp-P-1 and Trp-P-2 inhibited tryptophan hydroxylase competitively with the substrate and non-competitively with biopterin. These results suggest that food-derived heterocyclic amines may perturb the monoamine levels in the brain through the inhibition of the biosynthesis and metabolism of biogenic amines.
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PMID:Food-derived heterocyclic amines, 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole and related amines, as inhibitors of monoamine metabolism. 793 Dec 46

We report the sequence of the trpB gene of the cyanobacterium Synechocystis sp. PCC 6803. This gene was cloned from a plasmid library by functional complementation of a trpB mutant of Escherichia coli K-12. Among the known trpB sequences, the Synechocystis gene bears the greatest homology to the duplicated trpB genes of Arabidopsis thaliana and Zea mays. Southern and northern blotting analyses suggest that Synechocystis contains only a single trpB gene. In contrast to all other prokaryotes, Synechocystis has a trpB gene that is monocistronic. Attempts to construct a trpB null mutant of Synechocystis by standard techniques were unsuccessful, suggesting that this organism is unable to concentrate tryptophan from the external medium.
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PMID:Synechocystis PCC 6803 contains a single gene for the beta subunit of tryptophan synthase with strong homology to the trpB genes of Arabidopsis and maize (Zea mays L.). 815 86

Treatment of the ferredoxin-dependent, spinach glutamate synthase with N-bromosuccinimide (NBS) modifies 2 mol of tryptophan residues per mol of enzyme, without detectable modification of other amino acids, and inhibits enzyme activity by 85% with either reduced ferredoxin or reduced methyl viologen serving as the source of electrons. The inhibition of ferredoxin-dependent activity resulting from NBS treatment arises entirely from a decrease in the turnover number. Complex formation of glutamate synthase with ferredoxin prevented both the modification of tryptophan residues by NBS and inhibition of the enzyme. NBS treatment had no effect on the secondary structure of the enzyme, did not affect the Kms for 2-oxoglutarate and glutamine, did not affect the midpoint potentials of the enzyme's prosthetic groups and did not decrease the ability of the enzyme to bind ferredoxin. It thus appears that the ferredoxin-binding site(s) of glutamate synthase contains at least one, and possibly two, tryptophans. Replacement of either phenylalanine at position 65, in the ferredoxin from the cyanobacterium Anabaena PCC 7120, with a non-aromatic amino acid, or replacement of the glutamate at ferredoxin position 94, decreased the turnover number compared to that observed with wild-type Anabaena ferredoxin. The effect of the change at position 65 was quite modest compared to that at position 94, suggesting that an aromatic amino acid is not absolutely essential at position 65, but that glutamate 94 is essential for optimal electron transfer.
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PMID:The role of aromatic and acidic amino acids in the electron transfer reaction catalyzed by spinach ferredoxin-dependent glutamate synthase. 950 92

The lumenal CD loop region of the D2 protein of photosystem II contains residues that interact with a reaction center chlorophyll and the redox-active Tyr(D). Using combinatorial mutagenesis, photoautotrophic mutants of Synechocystis sp. PCC 6803 have been generated with multiple amino acid changes in this region. The CD loop mutations were transferred into a photosystem I-less Synechocystis strain to facilitate characterization of photosystem II properties in the mutants. Most of the combinatorial photosystem I-less mutants obtained had a high yield of variable fluorescence, F(V). However, in three mutants, which shared a replacement of Phe181 by Trp, the F(V) yield was dramatically reduced although a high rate of oxygen evolution was maintained. A site-directed F181W D2 mutant shared similar properties. Picosecond time-resolved fluorescence measurements revealed that in the combinatorial F181W mutants the fluorescence lifetimes in closed and open photosystem II centers were essentially identical and were similar to the fluorescence lifetime in open centers of the control strain. These results are explained by quenching of variable fluorescence in the mutants by charge separation between Trp181 and excited reaction center chlorophyll. This reaction competes efficiently with fluorescence and nonradiative decay in closed photosystem II centers, where the lifetime of the excitation in the chlorophyll antenna is long. Thermodynamic considerations favor the formation of oxidized tryptophan and reduced chlorophyll in the quenching reaction, presumably followed by charge recombination. A possible role of tryptophan-chlorophyll charge separation in the mechanism of energy-dependent quenching of excitations in photosynthesis is discussed.
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PMID:Tryptophan at position 181 of the D2 protein of photosystem II confers quenching of variable fluorescence of chlorophyll: implications for the mechanism of energy-dependent quenching. 1054 95

Pheochromocytomas are rare tumours, with an incidence of 1-2 per million which arise from chromaffin cells of the adrenal medulla. They occur sporadically or as part of dominantly inherited cancer syndromes like multiple endocrine neoplasia 2 (MEN2A and 2B) and others. Continuous cell lines, not available so far, are essential tools for studies in these tumours. A continuous cell line (KNA) was established from a sporadic pheochromocytoma of the right adrenal gland of a 73-year-old woman. The KNA cells grow as suspensions of spheroids and show the morphological and immunocytochemical characteristics of neuronal chromaffin cells, such as neuroendocrine granules, and positive reactions to chromogranin- and related peptide-, neuron specific enolase and vasoactive intestinal peptide antibodies. Neurite-like processes are formed after addition of nerve growth factor. Chromosomal analyses revealed a diploid (46,XX,n = 50) to hypodiploid (43-45,XX,n = 15) karyotype. In hypodiploid metaphases most frequently #19, #17, #21 and #22 were missing. Chromosome arms 1p and 4q showed apparently consistent interstitial deletions: 6q, 8q, 13q and 22q showed clonal interstitial deletions. The cell line shows a heterozygous sequence variant TGC (cysteine) to TGG (tryptophan) in codon 611 in exon 10 of the RET proto-oncogene. So far, PC-12, a rat adrenal pheochromocytoma, has been the only continuous pheochromocytoma cell line available. KNA represents the first report on a human continuous pheochromocytoma cell line, the first report of structural chromosome aberrations in pheochromocytomas and the first report of a RET mutation TGC to TGG in exon 10 of the RET proto-oncogene in a sporadic pheochromocytoma.
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PMID:First continuous human pheochromocytoma cell line: KNA. Biological, cytogenetic and molecular characterization of KNA cells. 1064 Jan 77


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