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)

Although increased levels of aluminum (Al) are present in patients with dialysis encephalopathy (DE), it is unclear if the association is causal. The enzyme dihydropteridine reductase (DHPR) plays a critical role in neurotransmitter formation and its activity. Elevated levels of Al are reported to decrease DHPR activity, which would alter neurotransmitter metabolism, thus producing DE. We examined the association between erythrocyte DHPR activity and Al levels, attention/psychomotor skills, and depression in a group of 21 patients with end-stage renal disease. DHPR activity was not related to Al level, mental status, psychomotor ability, or depression score. After administration of deferoxamine (an Al chelating agent), Al level increased significantly but DHPR activity remained the same. Our results suggest that the mechanism for the development for DE does not involve alterations of neurotransmitter metabolism caused by Al-mediated reductions in DHPR activity.
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PMID:Dihydropteridine reductase activity: lack of association with serum aluminum levels and cognitive functioning in patients with end-stage renal disease. 194 13

Tryptophan (Trp), as the precursor of serotonin, has been introduced in the treatment of depression and isomnia, but its clinical effectiveness must be considered with caution. In this presentation, the different aspects concerning the transport of Trp from the intestine to the brain and its enzymatic conversion into serotonin are discussed. The study of recent literature shows that the discussion about the relative importance of free and total plasma Trp and of the competitive large neutral amino acids for the transport of Trp into the brain continues. On the other hand, mainly animal studies demonstrate numerous regulatory processes, the importance of which has been underestimated until today. These processes concern enzymes like indoleamine-2,3-dioxygenase, cleaving Trp, but also quinoid-dihydropteridine reductase, producing the tetrahydrobiopterin necessary for Trp hydroxylase. It is proposed that the different steps leading from Trp to functionally active 5-HT are considered in a more systemic approach, taking into account that 5-HT synthesis depends on factors like depolarization of the nerve cell, endproduct inhibition, etc. In man, further studies are needed concerning the fate of Trp and competing compounds in the blood, after long-term treatment with Trp. In order to influence enzymatic mechanisms, clinical trials with compounds like tetrahydrobiopterin, acting directly on the enzymatic conversion of Trp into 5-HT, could lend new impulses to research on precursor therapy.
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PMID:Transport systems and enzymes involved in the metamorphosis of tryptophan into serotonin. 387 8

Tetrahydrobiopterin (BH(4)) cofactor is essential for various processes, and is present in probably every cell or tissue of higher organisms. BH(4) is required for various enzyme activities, and for less defined functions at the cellular level. The pathway for the de novo biosynthesis of BH(4) from GTP involves GTP cyclohydrolase I, 6-pyruvoyl-tetrahydropterin synthase and sepiapterin reductase. Cofactor regeneration requires pterin-4a-carbinolamine dehydratase and dihydropteridine reductase. Based on gene cloning, recombinant expression, mutagenesis studies, structural analysis of crystals and NMR studies, reaction mechanisms for the biosynthetic and recycling enzymes were proposed. With regard to the regulation of cofactor biosynthesis, the major controlling point is GTP cyclohydrolase I, the expression of which may be under the control of cytokine induction. In the liver at least, activity is inhibited by BH(4), but stimulated by phenylalanine through the GTP cyclohydrolase I feedback regulatory protein. The enzymes that depend on BH(4) are the phenylalanine, tyrosine and tryptophan hydroxylases, the latter two being the rate-limiting enzymes for catecholamine and 5-hydroxytryptamine (serotonin) biosynthesis, all NO synthase isoforms and the glyceryl-ether mono-oxygenase. On a cellular level, BH(4) has been found to be a growth or proliferation factor for Crithidia fasciculata, haemopoietic cells and various mammalian cell lines. In the nervous system, BH(4) is a self-protecting factor for NO, or a general neuroprotecting factor via the NO synthase pathway, and has neurotransmitter-releasing function. With regard to human disease, BH(4) deficiency due to autosomal recessive mutations in all enzymes (except sepiapterin reductase) have been described as a cause of hyperphenylalaninaemia. Furthermore, several neurological diseases, including Dopa-responsive dystonia, but also Alzheimer's disease, Parkinson's disease, autism and depression, have been suggested to be a consequence of restricted cofactor availability.
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PMID:Tetrahydrobiopterin biosynthesis, regeneration and functions. 1072 95

Oxidative stress is intimately involved in alcoholic cardiomyopathy. Catalase is responsible for detoxification of hydrogen peroxide (H(2)O(2)) and may interfere with ethanol-induced cardiac toxicity. To test this hypothesis, a transgenic mouse line was produced to overexpress catalase (~50-fold) in the heart, ranging from sarcoplasm, the nucleus and peroxisomes within myocytes. Mechanical and intracellular Ca(2+) properties were evaluated in ventricular myocytes from catalase transgenic (CAT) and wild-type FVB mice. Protein abundance of sarco (endo) plasmic reticulum Ca(2+)-ATPase (SERCA), phospholamban (PLB), Na(+)/Ca(2+) exchanger (NCX), dihydropyridine Ca(2+) receptor (DHPR), ryanodine receptor (RyR), Akt and phosphorylated Akt (pAkt) were measured by western blot. CAT itself did not alter body and organ weights, as well as myocyte contractile properties. Acute exposure of ethanol elicited a concentration-dependent depression in cell shortening and intracellular Ca(2+) in FVB mice with maximal inhibitions of 65.4% and 35.8%, respectively. The ethanol-induced cardiac depression was significantly attenuated in myocytes from CAT with maximal inhibitions of 42.4% and 27.3%. CAT also abrogated the ethanol-induced inhibition of maximal velocity of shortening/relengthening, prolongation of relengthening duration and intracellular Ca(2+) clearing time. Cell shortening at different extracellular Ca(2+) revealed stronger myocyte-shortening amplitude under lower (0.5 mM) Ca(2+) in CAT mice. Protein expression of NCX, RyR, Akt and pAkt were elevated in myocytes from CAT mice, while those of SERCA, PLB and DHPR were not affected. In conclusion, our data suggest that catalase overexpression may protect cardiac myocytes from ethanol-induced contractile defect, partially through improved intracellular Ca(2+) handling and Akt signaling.
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PMID:Cardiac-specific overexpression of catalase rescues ventricular myocytes from ethanol-induced cardiac contractile defect. 1278 82

We report an adult patient lacking endogenous synthesis of monoamines (dopamine, serotonin, and catecholamines) due to a severe dihydropteridine reductase (DHPR) deficiency. With levodopa and 5-hydroxytryptophan (5HTP) supplementation, the patient exhibited moderate mental retardation, acute episodes of parkinsonism, and episodes of depression. Despite the use of levodopa from age 3 months, he exhibited no dyskinesia or dopaminergic cell loss as suggested by normal PET imaging of the dopamine transporter.
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PMID:Dihydropteridine reductase deficiency: levodopa's long-term effectiveness without dyskinesia. 1719 Sep 55