Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acrylamide is an efficient quencher of tryptophanyl fluorescence which we report to be very discriminating in sensing the degree of exposure of this residue in proteins. The quenching reaction involves physical contact between the quencher and an excited indole ring, and can be kinetically described in terms of a collisional and a static component. The rate constant for the collisional component is a kinetic measure of the exposure of a residue in a protein, and values ranging from 4 X 10(9) M-1 S-1 for the fully exposed tryptophan in the polypeptide, adrenocorticotropin, to less than 5 X 10(8) M-1 S-1 for the buried residue in azurin have been found. Static quenching is readily detected in proteins that are denatured, or contain only a single fluorophor. Quenching patterns for most multi-tryptophan containing proteins are difficult to analyze precisely, but qualitative information can, nevertheless, be extracted. Applications of this probing technique for monitoring protein conformational changes, such as the acid-induced expansion of human serum albumin, and inhibitor binding to enzymes, are presented. The value of this method lies in its ability to sense not only the steady-state exposure of a residue in a protein, but also its dynamic exposure.
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PMID:Exposure of tryptophanyl residues in proteins. Quantitative determination by fluorescence quenching studies. 125 18

Cerebrospinal fluid (CSF) from 6 cases of asymptomatic infantile spasms (IS) (mean age, 6.1 months) was collected before and after treatment with adrenocorticotropic hormone (ACTH). The concentration of CSF tryptophan (TRP) metabolites was analyzed using HPLC and compared to the metabolite concentration in CSF from 10 age-matched controls (mean age, 6.7 months). Levels of CSF serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), and kynurenine (KYN) at pretreatment were significantly lower in IS patients compared to controls (p < 0.05). In contrast, the levels of CSF 3-hydroxykynurenine (3-OHKY) before ACTH treatment were significantly higher in IS patients than in controls (p < 0.05). After the treatment, significant increases in 5-HIAA and decreases in KYN and 3-OHKY levels (p < 0.05) were observed in CSF of infants whose seizures were eliminated by ACTH. These findings suggested that the presence of seizures in IS was associated with a significant decrease in serotonergic activity, or that the turnover in the direction of 3-OHKY was altered. The possibility that elimination of seizures by ACTH might be related to decreased production of kynurenine metabolites was discussed.
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PMID:[Changes in CSF tryptophan metabolite levels in infantile spasms]. 141 65

1. Like other authors we have established disturbances in central serotonergic neurotransmission in severely depressed patients by implementing hypothalamic pituitary adrenal (HPA)-axis hormones and prolactin responses to serotonin agonists or precursors. 2. Challenge probes with D,L fenfluramine have yielded controversial results. This substance, however, is not as serotonin-selective as previously believed. 3. Dextro(D)-fenfluramine, the dextrorotatory isomer of fenfluramine, constitutes a specific and potent serotonergic agonist. 4. In the present study the authors determined the following in healthy volunteers, and in depressed inpatients: the adrenocorticotropic hormone (ACTH), beta endorphin, prolactin and cortisol responses to D-fenfluramine administration (45 mg orally), total L-tryptophan and the 8 a.m. postdexamethasone cortisol values. 5. We found no significant differences in any of the post-D-fenfluramine hormone levels across healthy controls, minor, simple major and melancholic depressives. There were no significant correlations between L-tryptophan or postdexamethasone cortisol on the one hand, and any of the post-D-fenfluramine hormone values on the other.
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PMID:HPA-axis hormones and prolactin responses to dextro-fenfluramine in depressed patients and healthy controls. 166 3

Recently the pH gradient evoked by a K+ diffusion potential was shown to translocate a synthetic monobasic amphipathic hexapeptide across the bilayer of lipid vesicles (De Kroon, A.I.P.M., Vogt, B., Van 't Hof, R., De Kruijff, B. and De Gier, J. (1991) Biophys. J. 60, in press). Here this observation is extended by studying the effect of a membrane potential on a set of bioactive peptides. The panel of peptides comprises the toxin mastoparan X, a tryptophan-containing analogue of the presequence of the mitochondrial protein cytochrome oxidase subunit IV (preCoxIV(1-25)W18), and the regulatory peptides ACTH(1-24), alpha-MSH, ACTH(1-10), dynorphin A, bombesin, and LHRH. The interaction of these peptides with phospholipid vesicles has been measured using the intrinsic tryptophan residue as fluorescent probe. In the absence of a K+ diffusion potential only mastoparan X and the presequence show considerable binding to vesicles consisting of phosphatidylcholine (PC). In contrast, under these conditions all peptides display affinity for vesicles consisting of the acidic phospholipid cardiolipin (CL), the extent of which depends on the net positive charge of the peptide. Application of a K+ diffusion potential to large unilamellar vesicles (LUV) consisting of PC results in a time dependent tryptophan fluorescence increase for mastoparan X, which is accelerated upon incorporating increasing amounts of CL into the LUV. A similar fluorescence increase in response to a K+ diffusion potential was observed for the above model peptide. Yet the mechanism resulting in the fluorescence increase of mastoparan X is completely different from that of the hexapeptide. Binding experiments indicate that a membrane potential-induced enhanced binding of the peptide to the outer surface of the vesicles contributes to the fluorescence increase. PreCoxIV(1-25)W18, dynorphin A, and ACTH(1-24) show fluorescence responses upon applying a membrane potential that are consistent with that of mastoparan X, whereas the other peptides tested do not respond up to a LUV CL content of 50%. The results tentatively suggest that the membrane potential only affects a peptide when it has the ability to adopt a stable membrane bound conformation.
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PMID:The effect of a membrane potential on the interaction of mastoparan X, a mitochondrial presequence, and several regulatory peptides with phospholipid vesicles. 168 Mar 97

Cerebrospinal fluid (CSF) from 7 patients with infantile spasms (mean age: 6.7 months) was collected before and after treatment with adrenocorticotropic hormone (ACTH). The concentration of neurotransmitter metabolites was analyzed using high-performance liquid chromatography and compared to the metabolite concentration in the CSF from 7 age-matched controls (mean age: 6.1 months). Pretreatment levels of CSF 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid, 3-methoxy-4-hydroxyphenyl glycol (MHPG), and kynurenine were significantly lower in infantile spasm patients compared to controls. Following treatment, marked increases in 5-HIAA and decreases in kynurenine levels were observed in the CSF of the 5 infants whose seizures were eliminated or reduced by ACTH. In the 2 nonresponders 5-HIAA levels decreased. The level of MHPG was reduced slightly in 5 infants, including the 2 nonresponders, and was increased in 2 responders. CSF homovanillic acid levels increased in 4 infantile spasm infants and decreased in 3 following ACTH. These data demonstrate that the presence of seizures in infantile spasms is associated with a significant decrease in serotonergic activity and that elimination of seizures by ACTH is accompanied by increased serotonin turnover. The simultaneous increase of 5-HIAA and decrease of kynurenine, an alternate metabolite of tryptophan, suggests an underlying disturbance of tryptophan metabolism in infantile spasms. The possibility that elimination of seizures by ACTH may be related to decreased production of certain kynurenine metabolites, particularly quinolinic acid, is discussed.
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PMID:Changes in CSF neurotransmitters in infantile spasms. 172 2

The substrate specificity of polysome rat liver N alpha-acetyltransferase (NAT) has been examined by utilizing a series of synthetic and natural substrates that has been systematically altered with respect to N-terminal sequence and length. Families of peptides of the structure S-Y-S-G-G-L-L-L were generated by successively replacing the N-terminal serine, the penultimate tyrosine, and the antepenultimate serine with all 19 commonly occurring amino acids, which were then assessed for their reactivity with the rat liver enzyme. Only peptides with N-terminal serine, alanine, methionine, leucine, and phenylalanine were modified. Glycine, lysine, arginine, valine, isoleucine, and tryptophan in the second position are (with N-terminal serine) strongly inhibitory, and proline completely blocks modification. Third-position substitutions have less of an effect on NAT activity with glycine, aspartic acid, glutamic acid, and tryptophan being most inhibiting (with N-terminal Ser-Tyr). These observations are generally in agreement with in situ modifications although there are some significant differences particularly with respect to the amino-terminal residues. Optimal chain length was determined to be 10-11 residues with either synthetic peptides of the structure S-Y-S-(G)n-L-L-L or adrenocorticotropin (ACTH) sequences ranging from 8 to 39 residues. The ACTH peptides were generally found to be severalfold better substrates than the corresponding synthetic ones. Activity was not affected by increased chain length beyond approximately 17 residues. These data support the view that polysome-catalyzed N alpha-acetylation occurs as a cotranslational event on nascent chains of about 20-40 amino acids in length.
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PMID:Rat liver polysome N alpha-acetyltransferase: substrate specificity. 184 56

Eight women with prospectively documented premenstrual syndrome (PMS) underwent multiple samplings for estradiol, progesterone, prolactin, cortisol, and plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) during an asymptomatic midcycle (late follicular) and a symptomatic premenstrual (late luteal) phase of the menstrual cycle. Cerebrospinal fluid (CSF) was collected for analysis of MHPG, norepinephrine (NE), 5-hydroxyindoleacetic acid (5-HIAA), dihydroxyphenylacetic acid (DOPAC), gamma-aminobutyric acid (GABA), homovanillic acid (HVA), tyrosine, tryptophan, beta-endorphin, prostaglandins, adrenocorticotropic hormone (ACTH), and arginine vasopressin (AVP). In subsequent months, a dexamethasone suppression test (DST) and a thyrotropin-releasing hormone (TRH) stimulation test were performed during midcycle and premenstrual phases. Significant results included increased CSF concentrations of MHPG in the premenstrual, as compared with the midcycle, phase of the cycle, and increased plasma cortisol concentrations during the midcycle phase. The DST showed a 62% overall rate of nonsuppression, irrespective of menstrual cycle phase. Though there were no abnormalities of thyrotropin-stimulating hormone (TSH) after TRH stimulation, the mean delta maximum prolactin values after TRH stimulation were higher than reported normal values both at midcycle and premenstrually. These pilot data suggest hormonal axes that might be worthy of further systematic investigation in future studies of PMS.
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PMID:CSF and endocrine studies of premenstrual syndrome. 193 Jun 15

This review focuses on neurotransmitter and neuropeptide actions on food ingestion, as well as on some of the mechanisms that may lead to the development and maintenance of obesity. In particular, the role of hypothalamic amines (catecholamines, serotonin) in appetite control is described. Thus, hypothalamic noradrenaline appears to stimulate food intake, while an enhanced brain serotonergic neurotransmission leads to a suppression of food ingestion, preferentially of carbohydrate intake. The involvement of brain serotonin neurons in appetite control is most attractive, since serotonin synthesis and release is readily affected by either precursor loading (i.e., 1-tryptophan) or pharmacological manipulation (e.g., drugs such as fenfluramine or fluoxetine). Recent data now suggest that at least a subgroup of obese patients is characterized by a disturbed serotonergic neurotransmission, thus exhibiting behaviors such as carbohydrate craving. Among neuropeptides involved in appetite control, the most attractive candidate appears to be corticotropin-releasing hormone which is released by neurons of the paraventricular nucleus and produces a stress-like activation of the organism, and has a strong appetite-suppressant effect.
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PMID:[Central nervous appetite regulation: mechanisms and significance for the development of obesity]. 197 Jun 99

The main characteristics of L-tyrosine (L-Tyr) uptake by B16/F10 malignant melanocytes are reported. This amino acid can be taken up by two systems, both of them being saturable. The first one would be system L. This system can be studied in cells preloaded with amino acids that are a good substrate for system L, such as L-methionine or L-tryptophan. The kinetic parameters for L-Tyr uptake by this transport system are Vm = 6.5 pmol L-Tyr/10(3) cells.min and Km around 130 microM. The second system, probably the system ASC, shows lower capacity but higher affinity than the former. This system can be detected only in cells previously depleted of amino acids, showing approximate kinetic values of Vm 0.05 pmol L-Tyr/10(3) cells.min and Km around 5 microM. It is shown that the increase in cell density yields a decrease in the rate of L-Tyr uptake by system L, but this increase does not affect the high affinity system, alpha-MSH does not affect significantly the L-Tyr uptake by both systems. 2-Amino bicyclo-(2,2,1)-heptane-2-carboxylic acid produces a remarkable inhibition of the rate of L-Tyr uptake, but alpha-methylaminoisobutyric acid does not affect the rate of transport of this amino acid. The absence of sodium produces a slight but reliable decrease in the rate of L-Tyr uptake, supporting the involvement of two different transport systems. The ionophores monensin and nigericin enhance the transport by system L, but this effect is suppressed by the presence of ouabain. This finding indicates that the (Na+ -K+)-ATPase is essential for the stimulating action of ionophores.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Transport of L-tyrosine by B16/F10 malignant melanocytes: characterization of the process. 198 30

The hypothalamic-pituitary-adrenal (HPA) axis, the hypothalamic-pituitary-thyroid (HPT) axis, and the availability of L-tryptophan (L-TRP) to the brain were studied in their relationships to (1) 14 depressive symptoms measured by the Structured Clinical Interview for DSM-III-R--Patient Version (SCID) and (2) the cluster-analytically generated vital/nonvital classes. The following biological parameters were measured in 100 depressed females: free thyroxine (FT4), baseline thyroid stimulating hormone (TSH), predexamethasone and postdexamethasone cortisol and adrenocorticotropic hormone (ACTH) values, the circulating levels of total L-TRP, and the L-TRP/sum of competing amino acids ratio. We found that the psychopathological correlates of disorders in the HPA/HPT axis and of a decreased availability of L-TRP were vital symptoms, i.e., distinct quality of mood, nonreactivity, early morning awakening, anorexia-weight loss, and psychomotor disorders. There was no significant relationship between those biological markers and the nonvital symptoms of the SCID inventory for depressive symptoms. However, we did not validate our SCID clustering in vital and nonvital classes by qualitative differences in the biological variables. It was concluded that our nonvital/vital clusters should be regarded as continuous categories with regard to the biological markers studied; these clusters constitute relevant stages in the continuum of progressing biological dysfunction.
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PMID:Clinical subtypes of unipolar depression: Part III. Quantitative differences in various biological markers between the cluster-analytically generated nonvital and vital depression classes. 217 96


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