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

Metabolic compensation appears possible within the serotonergic, folate, purine system and it seems possible that clinical illness may result when the system can no longer compensate. For example, elevated serotonin, induced by stress accumulation of tryptophan, could be compensated by a lowered folate ratio, normalizing the beta-carboline index and preventing hallucinations. Conversely, deficient serotonin, induced by a psychological loss or transport deficit, could be compensated by raising the folate ratio, which would normalize the beta-carboline index and prevent further depression. Increased purine turnover would seemingly lower the folate ratio, compensating perhaps for hallucinatory activity or mania. Several genetic defects of enzymes or transport proteins could seemingly preclude normal compensations within the system.
 ...
PMID:Serotonin, folic acid, and uric acid metabolism in the diagnosis of neuropsychiatric disorders. 73 55

The effect of vitamin B-6 deficiency on excretion of tryptophan metabolites was compared in rats, guinea pigs, hamsters, and humans. With adequate vitamin B-6 intake, a high percentage of the tryptophan administered was excreted as kynurenic acid and quinolinic acid in rat urine, and as acetylkynurenine and kynurenine in hamster urine. None of the tryptophan metabolites measured in normal guinea pig urine or human urine accounted for more than 1% to 2% of the tryptophan administered. During vitamin B-6 deficiency, the percentages of the tryptophan load excreted as xanthurenic acid, kynurenine, and o-hydroxykynurenine, (which precede the 3-hydroxykynureninase step in the kynurenine pathway) were increased in all four species. However, the percentages excreted as 3-hydroxyanthranilic acid and quinolinic acid, which are beyond the 3-hydroxy-kynureninase step, responded differently. The 3-hydroxyanthranilic acid percentage was not changed in rat urine, but was increased in human and guinea pig urines. The quinolinic acid percentage was decreased in rat urine, unchanged in guinea pig and hamster urine, and increased in human urine. In rats, depression of 3-hydroxykynureninase activity was apparently the major factor causing a change in the pattern. However, in hamsters, kynurenine hydroxylase and o-hydroxykynureninanse activities apparently were depressed. In humans, 3-hydroxykynureninase activity also was apparently depressed and the total amount of administered tryptophan accounted fro in the urine as metabolites of the kynurenine pathway was increased. Levels of urinary metabolites reached a maximum in guinea pigs after only 1 week of consuming the vitamin B-6 deficient diet, suggesting that the vitamin deficiency developed very rapidly in this species.
 ...
PMID:Effects of vitamin B-6 deficiency and tryptophan loading on urinary excretion of tryptophan metabolites in mammals. 83 87

Tranylcypromine produces behavioral excitation while pargyline produces depression. Tranylcypromine increased brain tryptophan which led to an accumulation of tryptamine. The levels of tryptamine after tranylcypromine were found to be 3 times those found after pargyline.
 ...
PMID:Effects of tranylcypromine and pargyline on brain tryptamine. 87 Mar 36

The study dealt with the level of and diurnal alterations in the concentration of tryptophan, free tryptophan and tyrosine in the blood plasma of 20 inhibited depression patients and 10 healthy controls. The results suggested that there was no distinct relationship between either the total plasma tryptophan or plasma tyrosine level and depression. On the other hand, the free plasma tryptophan level was, at all the times of day at which measurements were made, either significantly or almost significantly higher in the patients than in the controls. It was further found that the results of measurement were related to the patients' clinical improvement, as measured by the Hamilton test, in such a way that after four weeks of treatment the free plasma tryptophan level in 'poorly improved' patients continued to be significantly higher in comparison with the controls, whereas the values for the 'well improved' patient group did not differ greatly from the corresponding values for the control group any longer. It may be hypothesized that the rise in the free plasma tryptophan in depressive patients might represent an effort made by the peripheral body to compensate for the slowed-up serotonin metabolism of the brain, whereby the tryptophan mobilized from the periphery would serve as a sort of 'endogenous antidepressant' provided by the organism itself.
 ...
PMID:The daily rhythm of plasma tryptophan and tyrosine in depression. 94 98

Exposure of dilute aqueous solutions of tryptophan to near UV light (320 to 390 nm) at subsolar levels yields fluorescent photoproducts capable of inhibiting the growth and differentiation of cultured mouse embryonic fibroblasts and fertilized sea urchin eggs. The ability of these cells to incorporate labelled precursors of protein, RNA, and DNA into their respective macromolecules was markedly inhibited by adding tryptophan preirradiated with near UV light to their incubation media. Thus the inhibition of growth and differentiation of these cells seems to result from a depression of their ability to synthesize macromolecules in the presence of the photoproducts.
 ...
PMID:Inhibition of cell growth by near ultraviolet light photoproducts of tryptophan. 94 71

By treating rats with lithium chloride or cocaine hydrochloride, or lithium chloride followed by cocaine hydrochloride, we have shown the antagonistic effects of these drugs on two mechanisms that may be involved in regulating serotonin 5-HT) synthesis in the striate cortex. Lithium chloride (5 to 10 meq/kg/day) stimulates the relative velocity of the active uptake of labelled tryptophan and proportionally enhances the conversion of labelled tryptophan to 5-HT in synaptosomally enriched preparations. With continued administration of lithium chloride, the activity of tryptophan hydroxylase from the median raphe and subsequently in lysed synaptosomal preparations from striate cortex is reduced; the substrate uptake remains enhanced, but the conversion of substrate to transmitter returns to control levels. In contrast, an injection of cocaine hydrochloride inhibits the high affinity uptake of tryptophan, reducing the conversion of the amino acid to 5-HT and resulting in an increase in the biosynthetic enzyme activity. However, administration of cocaine hydrochter three daily lithium chloride injections (10 meq/kg) results in no apparent effects on substrate uptake, conversion, or enzyme activity. We theorize that the effect of lithium was to push two regulatory parameters (the uptake of substrate and the enzyme activity) to their respective functional upper and lower limits, leaving the serotonergic neurons "buffered" against the "usual" effects of the stimulant drug, and offer this neurobiological model for consideration in relation to the clinical effects of lithium in the prophylaxis of both mania and depression in some patients.
 ...
PMID:A neurobiological model for the symmetrical prophylactic action of lithium in bipolar affective disorder. 98 97

Tryptophan and 5-hydroxyindoleacetic acid (precursor and metabolite respectively of 5-hydroxytryptamine) were determined in ventricular CSF of psychiatric patients undergoing stereotactic subcaudate tractotomy. Tyrosine and homovanillic acid (precursor and metabolite respectively of dopamine) were also determined. Results suggest an association between affective state and the above precursor amino acids with lower concentrations in primary depression and higher ones when anxiety or agitation predominate. This leads to lower 5-hydroxyindoleacetic acid concentrations in depression and higher concentrations in anxiety and agitation.
 ...
PMID:Precursors and metabolites of 5-hydroxytryptamine and dopamine in the ventricular cerebrospinal fluid of psychiatric patients. 99

The Authors describe the various anomalies of the metabolism of tryptophan that are observed in various diseases. The oxidative pathway is most important of the metabolic pathway of the amino acid; the degredation of tryptophan is particularly influenced by steroid hormones and vitamins' want. The metabolic anomalies are demonstrable both in malignant tumors (mostly in bladder cancer and Hodgkin's disease), both during psychiatric diseases (such as depression and schizophrenia) and in the diseases of connective tissue in addition to congenital errors of the degradation of tryptophan (such as Hartnup's disease, tryptophanuria and 3-hydroxychinureninuria). The metabolic pictures are manifest after amino acid's in the diseases of connective tissue but are independent for clinical seriousness and, in any case, less significant than those observed in other pathological pictures, mostly in Hodgkin's disease. The existence of anomalies of tryptophan's metabolism is certainly shown in many diseases, however the true physiopathogenetic meaning of these metabolic alterations is not yet specified. Particularly it is not definite if these alterations are the cause of diseases, which they appear in, or if they are secondary alterations.
 ...
PMID:[Clinical significance of changes in tryptophan metabolism]. 109 26

A summary of the effects of contraceptive pills on vitamins in the b lood is presented. The significant increase of Vitamin-A in the plasma of contraceptive users is believed to be a result of the increase of bet alipoprotein, which binds chiefly to Vitamin-A. Although high concentrations of Vitamin-A have caused teratogenicity in test animals, the increase found in humans using contraceptive pills is not high enough to cause risk. A lowering of Vitamin-B6 (pyridoxin) levels has occurred with the use of contraceptive pills. This can cause alteration in the metabolism of tryptophan, which could cause depression in pill users. The lack of pyridoxine can also increase the production of xanthuric acid which binds with insulin, resulting in a decreased glucose tolerance. A decrease in folic acid in pill users has also been observed, caused by some effect of the pill on the folate deconjugate. The Vitamin-B12 level is also lowered for unascertainable reasons related to the decrease in folic acid. No anemia occurs in spite of the lowered Vitamin-B complex levels in the blood. A lack in Vitamin-C in users of pills containing estrogens is possibly effected by a corresponding increase between estrogens and ceruloplasmin, a protein active in the oxidation of ascorbic acid. This lack of Vitamin-C has had no clinical significance thus far.
 ...
PMID:[P-pills and vitamins]. 114 66

This letter is a response to an article describing the efficacy of administering large doses of tryptophan to depressive patients taking oral contraceptives. This letter-writer argues that the salient action of mood elevation is a result of the supplemental pyridoxine (vitamin B) which ameliorates the deficiency induced by oral contraceptive use that leads to depression resulting from inhibition of synthesis of biogenic amines in the central nervous system. Instead of large doses of tryptophan, which may cause dangerous accumulations of possibly carcinogenic and diabetogenic metabolites when therapy for depression is indicated, pyridoxine should be administered together with the tryptophan; the tryptophan should be discontinued once the deficiency is corrected, although the vitamin therapy should continue throughout oral contraceptive use.
 ...
PMID:Letter: supplementary pyridoxine given to women using oral contraceptives. 115 24


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>