Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Some children with coeliac disease show behavioural disorders such as depression and other signs which have been correlated with reduced central monoamine metabolism. We have therefore investigated the brain availability of the monoamine precursors tryptophan and tyrosine in 15 untreated children with coeliac disease and 12 treated children with coeliac disease as well as in 12 control children. Significantly decreased plasma concentrations of tryptophan were found in untreated children (mean (SD) 13 (4) mumols/l, p less than 0.001) compared with treated children (31 (13) mumols/l), and in both groups of coeliac children when compared with control children (81 (22) mumols/l). A significantly lower ratio of plasma tryptophan to large neutral amino acids (tyrosine, valine, isoleucine, leucine, and phenylalanine) was also observed, which could indicate impaired brain availability of tryptophan in coeliac children and was more pronounced in untreated children. The impaired availability of tryptophan could produce decreased central serotonin synthesis and in turn behaviour disorders in children with coeliac disease.
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PMID:Plasma precursor amino acids of central nervous system monoamines in children with coeliac disease. 177 52

The deleterious effects of branched-chain amino acid (BCAA) antagonism caused by excess dietary leucine include growth depression and subnormal valine and isoleucine pools. To investigate mechanisms causing these changes, rats were gavage-fed low-protein (9%) diets with or without BCAA supplements, and the metabolism of another BCAA (valine) was measured in incubated rat epitrochlearis muscles. A 10% leucine supplement (HL-10) inhibited growth; growth remained subnormal even when 2.6% isoleucine and 2.4% valine (HLIV-10) were added to the diet. Valine decarboxylation in muscle increased 170-270% in rats fed the HL-10 or HLIV-10 diets, but was still markedly lower than we previously found in muscle of rats fed a 14% protein diet. Valine incorporation into muscle protein as an estimate of protein synthesis was unaffected by any of the BCAA supplements. When a lower (4%) concentration of leucine (without or with 0.16% isoleucine and 0.16% valine) was studied, growth was also suppressed but only if rats had not been preconditioned to 9% protein. Although increased BCAA decarboxylation in muscle caused by excess dietary leucine contributes to low valine and isoleucine pools, abnormal growth appears to be independent of low valine and isoleucine levels and is not reflected in suppression of valine incorporation into muscle protein.
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PMID:Leucine-induced amino acid antagonism in rats: muscle valine metabolism and growth impairment. 200 1

Plasma and brain amino acid and plasma branched-chain alpha-keto acid (BCKA) concentrations were measured in rats fed diets containing high levels of individual amino and alpha-keto acids. Consumption of a low-protein (9% casein) diet high in leucine or alpha-ketoisocaproate depressed plasma concentrations of isoleucine and valine and their respective keto acids, alpha-keto-beta-methylvalerate and alpha-ketoisovalerate. High dietary levels of alpha-keto-beta-methylvalerate or alpha-ketoisovalerate (but not of isoleucine or valine) depressed plasma concentrations of the other BCKA and their respective branched-chain amino acids (BCAA). Consumption of a low protein, high phenylalanine diet depressed plasma concentrations of both BCAA and BCKA. Brain large neutral amino acid pools of rats fed all low-protein, high-amino acid diets were depleted. Consumption of diets high in individual BCKA increased brain concentrations of aromatic amino acids. In this study of rats allowed to feed for only 6 h/d, elevated brain phenylalanine concentration was associated with a significant depression of food intake, whereas elevated brain BCAA concentrations were not. Also, elevated plasma BCKA concentrations, comparable with those observed in maple syrup urine disease, were accompanied by elevations in concentrations of aromatic amino acids in brain but not in plasma.
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PMID:High levels of dietary amino and branched-chain alpha-keto acids alter plasma and brain amino acid concentrations in rats. 201 76

The role of serotonin3 (5-HT3) receptors in the initial food intake depression of rats ingesting amino acid imbalanced or high-protein diets was investigated. The 5-HT antagonists metergoline, pirenpirone, ICS 205-930, and MDL 72222, the dopamine antagonist pimozide, or the alpha-adrenergic antagonist phentolamine were injected 15-45 min before presentation of test diets. Food intake was measured at intervals for 3 days. The 5-HT3 antagonists, ICS 205-930 and MDL 72222, restored feeding of a mild isoleucine (Ile)-imbalanced diet to control levels, although MDL 72222 had a longer time course of action. ICS 205-930 also increased intake of a severe Ile-imbalanced diet and Thr-imbalanced diet but not a high-protein (44% casein) diet. Treatment with metergoline, which blocks 5-HT1, 5-HT2, and dopamine receptor sites but not 5-HT3 sites, increased intake of the basal diet at 3 and 6 h but did not significantly alter intake of the mild Ile-imbalanced diet. Although pimozide tended to increase intake of the mild imbalanced diet, neither dopamine nor alpha-adrenergic receptor antagonism significantly affected imbalanced diet intake. Thus 5-HT3 receptors may mediate the anorexigenic activity of 5-HT associated with feeding an amino acid-imbalanced diet.
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PMID:Serotonin3 receptor antagonists block anorectic responses to amino acid imbalance. 211 34

1. The plasma levels of L-tryptophan (L-TRP) and the sum of five competing amino acids (CAA) namely tyrosine, phenylalanine, valine, leucine, isoleucine, were determined in 79 depressed females categorized according to the DSM-III. 2. In these patients the authors measured several parameters known to affect the availability of the above amino acids, i.e. triidothyronine (FT3) and thyroxine (FT4), vanilylmandelic acid (VMA), noradrenaline and adrenaline in 24 hr urine, the sex hormonal and nutritional state. 3. The 1 mg dexamethasone suppression test was performed and the pre and postdexamethasone cortisol and adrenocorticotropic hormone (ACTH) levels were determined at 8 a.m. 4. L-TRP and the ratio L-TRP/CAA were significantly lower in severely depressed females (296.X3, 296.X4) as compared with minor (300.40, 309.00) and simple major depressives (296.X2). The ratio L-TRP/CAA performed well as a clinical tool separating melancholic from minor depression. 5. FT3, FT4, VMA and noradrenaline were significantly increased in the severely depressed females, but these data did not correlate with the availability of L-TRP. Neither baseline cortisol nor the sex hormonal, nor the nutritional state related to the L-TRP data. The ratio L-TRP/CAA was significantly and negatively correlated with the postdexamethasone cortisol and ACTH values.
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PMID:The decreased availability of L-tryptophan in depressed females: clinical and biological correlates. 217 60

The role of adrenal function in the anorectic response and adaptation of rats to a diet with an isoleucine (Ile) imbalance was investigated. In the first of four experiments, rats were fed a mildly Ile-imbalanced diet after treatment with metyrapone, and inhibitor of glucocorticoid synthesis. In two separate experiments, rats were presented with either a mildly or severely Ile-imbalanced diet (4.93 and 9.86% imbalanced amino acid mixture, respectively) after bilateral adrenalectomy. Finally, the effects of ICS 205-930, a serotonin-3 receptor antagonist, on the intake of mildly Ile-imbalanced diet were tested in adrenalectomized animals. In each experiment a 2 X 2 factorial design was used. Neither metyrapone nor adrenalectomy altered the initial depression in the intake of an imbalanced diet. The adaptation phase in the response of adrenalectomized rats fed a mildly Ile-imbalanced diet was not different from that of controls, but adrenalectomized rats fed severely Ile-imbalanced diets were unable to adapt. Adrenalectomy did not alter the anti-anoretic activity of ICS 205-930 in this model. These results suggest that adrenal hormones are not necessary for the initial anoretic response or adaptation of rats to an Ile-imbalanced diet, nor are they implicated in the anti-anorectic effect of serotonin-3 blockade.
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PMID:Adrenal hormones and the anorectic response and adaptation of rats to amino acid imbalance. 226 7

The effects of bovine beta-casomorphin(1-7) (Tyr-Pro-Phe-Pro-Gly-Pro-Ile) on neonatal sleep in rats were studied. The pups received intraperitoneal injections of beta-casomorphin(1-7) (1 mg, 5 mg, 10 mg, 50 mg, or 100 mg/kg) or a corresponding volume of sodium chloride. In any of the doses used, beta-casomorphin(1-7) had no effect on waking. Only 100 mg/kg caused significant changes in sleep: the percentage of quiet state of the total recording time (TRT) increased and the percentage of active sleep decreased. Beta-casomorphin(1-7) did not cause significant respiratory depression. Naloxone pretreatment (1 mg/kg IP) reversed the effects of beta-casomorphin(1-7) on sleep, a finding which suggests that opiate mu-receptors are involved in mediating the sleep effects of beta-casomorphin.
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PMID:Effect of beta-casomorphin on neonatal sleep in rats. 234 85

The role of serotonin in the anorexic response of rats to an amino acid-imbalanced diet was investigated. After chronic depletion of serotonin with parachlorophenylalanine (PCPA, 300 mg/kg) or 5,7-dihydroxytryptamine (DHT, 200 micrograms/rat, intracisternally), initial intake of a mild isoleucine-imbalanced diet was reduced by 60% vs. a 17% reduction after saline injection. After acute treatment with the agonist, quipazine (quip, 5 mg/kg ip) or the precursor, tryptophan (TRP, 1% added to the diet), imbalanced diet intake was also exacerbated. PCPA and DHT may have caused receptor supersensitivity, such that the food intake depression after serotonin depletion was similar to that seen with the quip and TRP treatments. Injection of the autoreceptor agonist, 8-hydroxy-2(di-n-propylamino)tetralin (8-OH-DPAT, 500 micrograms/kg sc), to reduce transmission in the serotonergic systems resulted in an attenuation of the usual food intake depression of the amino acid-imbalanced diet (only a 7%, nonsignificant reduction). Also measurements made in the absence of pharmacological treatment showed that the ratio 5-hydroxyindole acetic acid-to-serotonin, a putative index of serotonin turnover, was increased 155% in the raphe nuclei and 140% in the hippocampus 3.5 h after ingestion of the mild isoleucine-imbalanced diet. Therefore increased serotonergic activity in some brain areas may be associated with the initial depression of food intake in rats fed an imbalanced amino acid diet.
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PMID:Serotonin and feeding responses of rats to amino acid imbalance: initial phase. 244 14

The depression of milk protein percentages for cows fed high fat diets in early lactation is a major problem facing the dairy industry. In order to describe more fully the mechanism involved, data involved 97 cows observations were summarized. Cows were fed diets containing corn-soybean meal or additional fat in the form of whole oilseeds as the main ingredients in the concentrate mix. Blood samples from the tail artery and subcutaneous abdominal vein were taken approximately 6- to 8-wk postpartum for amino acid analyses. Production of milk during the week of blood sampling was increased (36.9 and 39.6 kg/d) approximately 7.3% but milk protein percentages (2.91 and 2.79) were reduced for cows fed added fat. Intake of DM (21.1 and 21.4 kg/d) and BW (605 and 608 kg) were similar. Uptake of amino acids by the mammary gland, as measured by arteriovenous differences, was numerically lower for all essential amino acids and significantly reduced for histidine, isoleucine, leucine, phenylalanine, threonine, valine, and total essential amino acids for cows fed added fat. It is proposed that added fat inhibits somatotropin release from the anterior pituitary, thereby reducing mammary gland uptake of amino acids because of the role of somatotropin in aiding amino acid uptake. Administration of exogenous somatotropin with added fat diets may alleviate milk protein depression associated with such diets.
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PMID:Model to describe and alleviate milk protein depression in early lactation dairy cows fed a high fat diet. 262 49

The three-dimensional structure of the native unliganded form of the Leu/Ile/Val-binding protein (Mr = 36,700), an essential component of the high-affinity active transport system for the branched aliphatic amino acids in Escherichia coli, has been determined and further refined to a crystallographic R-factor of 0.17 at 2.4 A resolution. The entire structure consists of 2710 non-hydrogen atoms from the complete sequence of 344 residues and 121 ordered water molecules. Bond lengths and angle distances in the refined model have root-mean-square deviations from ideal values of 0.05 A and 0.10 A, respectively. The overall shape of the protein is a prolate ellipsoid with dimensions of 35 A x 40 A x 70 A. The protein consists of two distinct globular domains linked by three short peptide segments which, though widely separated in the sequence, are proximal in the tertiary structure and form the base of the deep cleft between the two domains. Although each domain is built from polypeptide segments located in both the amino (N) and the carboxy (C) terminal halves, both domains exhibit very similar supersecondary structures, consisting of a central beta-sheet of seven strands flanked on either side by two or three helices. The two domains are far apart from each other, leaving the cleft wide open by about 18 A. The cleft has a depth of about 15 A and a base of about 14 A x 16 A. Refining independently the structure of native Leu/Ile/Val-binding protein crystals soaked in a solution containing L-leucine at 2.8 A resolution (R-factor = 0.15), we have been able to locate and characterize an initial, major portion of the substrate-binding site of the Leu/Ile/Val-binding protein. The binding of the L-leucine substrate does not alter the native crystal structure, and the L-leucine is lodged in a crevice on the wall of the N-domain, which is in the inter-domain cleft. The L-leucine is held in place primarily by hydrogen-bonding of its alpha-ammonium and alpha-carboxylate groups with main-chain peptide units and hydroxyl side-chain groups; there are no salt-linkages. The charges on the leucine zwitterion are stabilized by hydrogen-bond dipoles. The side-chain of the L-leucine substrate lies in a depression lined with non-polar residues, including Leu77, which confers specificity to the site by stacking with the side-chain of the leucine substrate.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Periplasmic binding protein structure and function. Refined X-ray structures of the leucine/isoleucine/valine-binding protein and its complex with leucine. 264 82


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