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)

After surgical placement of end-to-side portacaval shunts (PCS), 4 adult mongrel dogs (11.8 to 18.2 kg) were fed purified diets and monitored for approximately 50 weeks for changes in body weight, neurologic status, and an array of clinically important biochemical variables. Two healthy dogs, fed the same diets and maintained in the same environment, were also observed (controls). Body weights were relatively stable over the period of observation. The branched-chain ratio ([valine] + [leucine] + [isoleucine]/[phenylalanine] + [tyrosine]), an index of the degree of change in plasma amino acid concentrations, was significantly lower in dogs with PCS than in controls. Despite this depression in branched-chain ratio, the principals (dogs with PCS) were essentially free of neurologic symptoms. Statistically significant decreases due to portacaval shunting were seen in the serum concentrations of glucose, calcium, urea nitrogen, creatinine, cholesterol, and albumin. Total protein, globulin, and triglyceride concentrations tended to be lower in the serum of principals than in serum of controls, but the differences were not statistically significant. Statistically significant increases due to portacaval shunting were seen in plasma concentrations of total conjugated bile acids and sulfobromophthalein retention. Concentrations of the following compounds tended to be higher in serum of principals than in serum of controls: phosphorus, chloride, uric acid, total bilirubin, lactate dehydrogenase, aspartate transaminase, alanine transaminase, and alkaline phosphatase. Liver biopsy at 7 months after operation showed mild-to-extensive atrophy of hepatocytes, mild-to-extensive fibrosis, and collapsed portal veins in all principals examined.
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PMID:Long-term biochemical and physiologic effects of surgically placed portacaval shunts in dogs. 395 18

Regulatory 5-DL-methyltryptophan (5-MT)-resistant mutants of facultative methylotrophic Pseudomonas sp. M. were obtained. They are able to excrete tryptophan into the growth medium (60 to 300 g/ml). 5-MTR regulatory mutants are characterized by depression of trpE, trpD and trpC genes, which causes the production of intermediates of tryptophan biosynthesis and results in trpA and trpB genes induction as well as in two-fold activation of N-5-phosphoribosyl anthranilateisomerase (trpF gene product). Besides, all mutants demonstrate reduction of synthase feed-back inhibition about 4-11-fold. Together with tryptophan excretion, 5-MTR regulatory mutants are able to excrete tyrosine and unable to utilize this amino acid as the sole carbon source, which points to multiple nature of the selective effect of 5-MT.
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PMID:[The tryptophan operon of the facultative methylotrophic bacteria Pseudomonas sp. M. III. Characteristics of regulatory 5-MTR mutants]. 395 24

The refined high resolution crystal structure of the bovine phospholipase A2 was compared with its counterpart from the venom of Crotalus atrox, the western diamondbacked rattlesnake. The strong similarity in their backbone conformations forms the basis of a common numbering system for the amino acid sequence. The three common major helices and much of the extended chain form a nearly identical "homologous core" structure. The variations in conformation usually arise from deletions/insertions or en bloc shifts of structural units. The exception to this is part of the highly conserved calcium-binding loop; however, this is to be expected as 1) there is no calcium ion sequestered in the venom dimer as there is in the case of the bovine enzyme and 2) two side chains in that segment form dimer-stabilizing interactions between the subunits of the C. atrox enzyme. The absolutely conserved catalytic network of hydrogen-bonded side chains formed by His 48, Tyr 52, Tyr 73, and Asp 99, as well as the hydrophobic wall that shields it, are virtually superimposable in the two structures. However, the details of the structural relationship between the amino terminus and the catalytic network differ in the two species and the ordered water molecules thought to be either functionally or structurally important in the pancreatic enzymes are not found in the crystal structure of the phospholipase A2 from C. atrox. The most striking difference from a functional standpoint is the fact that the surface depression in the region of the catalytic network that has been commonly considered the active site is shielded substantially in forming the intersubunit contact surface of the dimeric venom enzyme.
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PMID:A comparison of the crystal structures of phospholipase A2 from bovine pancreas and Crotalus atrox venom. 404 72

Two healthy adults with low fumarylacetoacetase activity in fibroblasts and lymphocytes, one a compound heterozygote for the tyrosinaemia and the pseudodeficiency genes and the other a homozygote for the pseudodeficiency gene, produced substantial amounts of succinylacetone when given an intravenous homogentisate load. The level of metabolites correlated with the residual enzyme activity and the genotype, being higher in the compound heterozygote. This subject also showed a small increase of metabolites in urine after an oral tyrosine load. In the pseudodeficiency homozygote a depression of erythrocyte delta-aminolevulinate dehydratase activity was observed after the tyrosine load. In fasting state both individuals have erythrocyte delta-aminolevulinate dehydratase activity below the reference range, indicating a persistently raised concentration of metabolites. Thus, the pseudodeficiency state is not just an in vitro phenomenon, but results in a definite reduction of enzyme activity in vivo. We speculate that the variant gene may predispose to the development of liver disease, possibly not recognized as tyrosinaemia.
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PMID:Concentrations of succinylacetone after homogentisate and tyrosine loading in healthy individuals with low fumarylacetoacetase activity. 406 34

Acute, uncontrollable stress increases norepinephrine (NE) turnover in the rat's brain (depleting NE) and diminishes the animal's subsequent tendency to explore a novel environment. Pre-treatment with tyrosine can reverse these adverse effects of stress, presumably by preventing the depletion of NE in the hypothalamus. Numerous studies suggest that NE inhibits the release of adrenocorticotropic hormone (ACTH) by suppressing corticotropic releasing factor (CRF) secretion in the hypothalamus. In the present study, we found that pre-treatment with supplemental tyrosine not only prevented the behavioral depression and hypothalamic NE depletion observed after an acute stress, but also suppressed the rise in plasma corticosterone. These results support a role for brain NE in stress-induced corticosterone secretion and demonstrate that supplemental tyrosine can protect against several adverse consequences of such stress.
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PMID:Dietary tyrosine suppresses the rise in plasma corticosterone following acute stress in rats. 406 99

Mice were fed diets deficient in a single essential amino acid, and the primary immune responses to inoculation of allogenic tumor cells was measured by in vitro assay of cellular immunity. Moderate reduction of the amino acids phenylalanine-tyrosine, valine, threonine, methionine-cystine, isoleucine, and tryptophane in the diet produced profound depression of hemagglutinating and blocking antibody responses, although cytotoxic cell-mediated immunity remained intact. These diets had previously been shown to result in a selective depression of tumor growth in mice. Limitation of the amino acids arginine, histidine, and lysine in the diets gave rise to only slight depression of the immune responses. These diets had previously been shown to produce a proportional decrease in both tumor growth and host body weight. Moderate leucine restriction resulted in a paradoxical depression of cytotoxic cell-mediated immunity with little effect on serum blocking activity. Slight increases had previously been noted in the weight of tumors in mice fed leucine-restricted diets. Deficiency or imbalance of essential amino acids in the diet may produce profound depression of immune responses and apparent, marked changes in the immune resistance of the host animal to tumors.
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PMID:Quantitative effects of nutritional essential amino acid deficiency upon immune responses to tumors in mice. 468 18

1. The drug HA-966 (1-hydroxy-3-amino-pyrrolidone-2), which chemically resembles the cyclic form of GABA, has been studied for neuro-pharmacological properties and for effects on the catecholamine content of the corpus striatum.2. The acute effects on spontaneous behaviour of rodents included flaccid catalepsy and reversible tranquillization in doses which were 5% or less of the lethal dose. Long lasting depression of the CNS, followed by complete recovery, was produced in the cat and the dog. In the monkey HA-966 caused periodical sleeping episodes.3. The exploratory behaviour and the amphetamine-induced motor activity in mice were blocked by HA-966. The toxicity of amphetamine in aggregated mice was only moderately reduced, suggesting that HA-966 differs from neuroleptics.4. Tremors induced by chemical agents (nicotine, zinc and tremorine) were markedly inhibited by HA-966. The muscarinic effects of tremorine were not reduced by HA-966, indicating a selective central antitremor effect.5. HA-966 elevated the threshold to strychnine convulsions and abolished the ipsilateral flexor reflex, while not having motor endplate blocking properties. It is suggested that HA-966 depresses central internuncial neurones.6. In rats and rabbits HA-966 produced synchronous EEG and inhibited the sensory arousal in doses not causing sedation. In the monkey the drug caused a periodical dissociation between ;sleep-EEG' and behaviour.7. In rat brain, HA-966 selectively elevated the dopamine content in the corpus striatum, while no changes in noradrenaline and 5-hydroxytryptamine contents could be demonstrated. The effect was still present when dopa synthesis was inhibited with alpha-methyl-p-tyrosine.8. Several effects of intravenously administered HA-966 became manifest after an appreciable delay and in hepatectomized mice the effects were much reduced. It is postulated that HA-966 is converted to a pharmacologically active metabolite.9. The results are discussed in the light of current views on drug therapy in extrapyramidal conditions and a GABA-related hypothesis as to the mode of action of HA-966 is presented.
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PMID:1-Hydroxy-3-amino-pyrrolidone-2(HA-966): a new GABA-like compound, with potential use in extrapyramidal diseases. 515 20

The beta-adrenergic agonist isoprenaline: Causes a decrease in most amino acids in plasma. Changes the relation between the large neutral amino acids in plasma in favor of tyrosine and Try. Causes an increase in brain concentrations of tyrosine and Try. Causes an increase in brain concentrations of DOPA and Try after the administration of these amino acids. The reported effects might be of clinical importance in the treatment of mental depression and other diseases where amino acids are used as therapeutic agents.
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PMID:Beta-adrenergic influence on brain concentrations of monoamine precursors. 608 29

Tryptophan hydroxylase (TPH) activity was measured in various rat brain regions after administering large doses of methamphetamine (METH). After four sequential doses of METH (15 mg/kg), given every 6 hr, TPH activity was decreased (to approximately 10% of control) in both the neostriatum and hippocampus. The depression of enzyme activity persisted for at least 30 days. When compared with the depression of neostriatal tyrosine hydroxylase activity, the depression of neostriatal and hippocampal TPH activity occurred sooner and was more pronounced. The depression of TPH activity was dependent on the number of doses and the amount of drug administered. Five days after one to two doses of METH, a transient recovery was observed but when four doses were given, the enzyme was depressed. No decrease in TPH activity was observed in brain areas containing serotonergic cell bodies. Agents which prevent the METH-induced decrease of neostriatal tyrosine hydroxylase activity, i.e., haloperidol, alpha-methyl-p-tyrosine and gamma-aminobutyric acid transaminase inhibitors also prevented the decrease in TPH activity caused by METH. In addition, fluoxetine, an inhibitor of 5-hydroxytryptamine re-uptake, prevented the METH-induced decrease in neostriatal and hippocampal TPH activity but did not alter the decrease in nenostriatal tyrosine hydroxylase activity.
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PMID:Long-term effects of multiple doses of methamphetamine on tryptophan hydroxylase and tyrosine hydroxylase activity in rat brain. 610 22

The rates of synthesis of serotonin, acetylcholine, and, under certain circumstances, dopamine and norepinephrine by brain neurons depend considerably on the availability to brain of the respective dietary precursors. This precursor dependence seems to be related to the fact that the enzyme catalyzing the rate-limiting step in the synthetic pathway for each transmitter is unsaturated with substrate at normal brain concentrations. Moreover, brain levels of the individual precursors rise following oral or parenteral administration of the pure compound or the ingestion of certain foods. Precursor-induced increases in brain transmitter formation seem to influence a variety of brain functions and behaviors, which suggests that transmitter release has been enhanced. It now appears that these precursors may become useful as therapeutic agents for the treatment of selected disease states, wherein the disease is related to reduced release of transmitter. Examples of Parkinson's disease (tyrosine), myasthenia gravis (choline or phosphatidylcholine), depression (tyrosine), and possibly abnormal appetite (tryptophan). Perhaps the future will bring the identification of still other neurotransmitters, whose rates of synthesis depend on precursor availability. Two potential candidates for which some information is already available are glycine (a spinal cord transmitter) and the prostaglandins (some of which may function as neuromodulators or transmitters) (48, 49). Each time a new precursor-product relationship is described, an opportunity becomes available for determining whether the precursor might be useful in treating disease states related to reduced transmitter release by neurons. The opportunities are worth exploring, since the use of a natural dietary constituent, even in purified form, is likely to produce fewer unwanted side-effects than are seen following administration of synthetic drugs.
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PMID:Dietary precursors and brain neurotransmitter formation. 611 81


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