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)

1 Pretreatment of rats with intraperitoneal injections of lead was shown to result in a depression of the microsomal mixed function oxidase system, as assessed by a decrease in hepatic microsomal P-450 and b5 content and by a decrease in the activity of the enzymes aniline hydroxylase and aminopyrine demethylase. Lead had a more marked effect on cytochrome P-450 than b5. 2 The activity of the rate-limiting enzyme of haem biosynthesis, delta-aminolaevulinic acid synthase, was inversely correlated with the microsomal cytochrome P-450 content. 3 The activity of the haem biosynthetic enzymes delta-aminolaevulinic acid dehydratase, coproporphyrinogen oxidase and ferrochelatase were decreased by increasing lead pretreatment. 4 The activity of the haem catabolic enzyme, haem oxygenase, was increased by lead pretreatment.
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PMID:Hepatic drug metabolism and haem biosynthesis in lead-poisoned rats. 65 97

1. The activities of six of the enzymes of haem biosynthesis have been assayed in peripheral blood from patients with lead poisoning, acute intermittent porphyria or hereditary coproprophyria. 2. Compared with normal subjects the lead-poisoned subjects had highly significant depression of delta-aminolaevulinate dehydratase, coproporphyrinogen oxidase and ferrochelatase. 3. Lead-poisoned subjects had highly significant elevation of delta-aminolaevulinate synthase activity. 4. delta-Aminolaevulinate synthase activity was inversely related to the haemoglobin concentration. 5. Increased delta-aminolaevulinate synthase and decreased delta-aminolaevulinate dehydratase activity are also found in acute intermittent porphyria. 6. Increased delta-aminolaevulinate synthase, normal prophobilinogen deaminase and uroporphyrinogen decarboxylase and decreased coproporphyrinogen oxidase are found in both lead poisoning and hereditary coproporphyria. 7. These enzyme changes explain the recognized patterns of porphyrins and prophyrin precurosrs in blood and urine in these conditions.
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PMID:Alterations in the activity of enzymes of haem biosynthesis in lead poisoning and acute hepatic prophyria. 91 57

The HEM13 gene of Saccharomyces cerevisiae codes for coproporphyrinogen oxidase (EC 1.3.3.3) catalyzing the sixth enzymic step in the heme biosynthetic pathway. Its expression has been previously shown to be regulated negatively by heme and oxygen. We have isolated the HEM13 gene by functional complementation of a hem13 gene by functional complementation of a hem13 mutant and determined its nucleotide sequence. The open reading frame encodes a protein of 328 amino acids. Its calculated molecular weight (37,673), amino acid composition and amino-terminal sequence predicted from the DNA sequence are in agreement with those determined for the native enzyme (Camadro, J. M., Chambon, H., Jolles, J., and Labbe, P. (1986) Eur. J. Biochem. 156, 579-587). The 5' ends of the HEM13 transcripts were identified by nuclease S1 mapping; induction of HEM13 resulted in an equivalent increase of the level of all the transcripts. 5' deletion analysis revealed that DNA sequence located upstream of 409 nucleotides from the translational initiation codon was needed for depression under oxygen limitation. The loss of induction of coproporphyrinogen oxidase activity by anaerobiosis caused a considerable decrease of heme formation in anaerobic cells.
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PMID:Isolation, sequence, and regulation by oxygen of the yeast HEM13 gene coding for coproporphyrinogen oxidase. 283 78

Acute toxic effects of lead were evaluated on porphyrin synthesis and coproporphyrinogen oxidase (CO) activity in an in vitro model, using HepG2 cells, a hepatoma cell line of human origin. Lead concentrations for exposure treatments were 0.5, 1.0, 2.5, 5.0 microM. No significant changes were found in treated cells with respect to uroporphyrin cellular or media concentrations. Cellular protoporphyrin increased in dose response shape, but no changes in extracellular content were found. Extracellular coproporphyrin concentration increased in a dose response manner without changes in cellular content. The CO activity was depressed in dose response shape, reaching 62% of control activity at 5.0 microM of lead treatment. The CO activity in Pb-treated cells was recovered after dithiothreitol (DTT) treatment, suggesting that sulphydryl groups play an essential role in the enzyme activity. The dose-response increase of coproporphyrin secretion accompanied by the depression of CO activity supports the suggestion that lead causes CO inhibition, as observed in this cellular model.
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PMID:Effect of acute lead treatment on coproporphyrinogen oxidase activity in HepG2 cells. 967 64

The bioaccumulations of lead in the liver and hepatic microsomes of fish after 1, 3, 7, 14, 28, and 45 days exposure were studied. In addition, the relationship between the bioaccumulated lead in both hepatic microsomes and the liver and their haem biosynthetic enzymes were studied. Lead toxicity was shown to result in a depression of the microsomal mixed function oxidase system, as assessed by a decrease in hepatic microsomal cytochrome P-450 and b5 content and by a decrease in the activity of the enzymes aniline hydroxylase and aminopyrine demethylase. Lead had a more marked effect on cytochrome P-450 than b5. The activity of the rate-limiting enzyme of haem biosynthesis, delta-aminolevulinic acid synthase, was inversely correlated with the microsomal cytochrome P-450 content. The activity of the heam biosynthetic enzymes delta-aminolevulinic acid dehydratase, coproporphyrinogen oxidase and ferrochelatase were decreased by increasing lead pretreatment. The activity of the haem catabolic enzyme, haem oxygenase, was increased by concentration and length of time to lead exposure.
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PMID:The effect of lead bioaccumulation on haem biosynthetic enzymes in fish. 1525 3

We previously described a polymorphism in exon 4 of the gene encoding the heme biosynthetic pathway enzyme, coproporphyrinogen oxidase (CPOX4), which significantly modifies the effect of mercury exposure on urinary porphyrin excretion in humans. Here, we examined potential consequences of this polymorphism ("CPOX4") on performance within neurobehavioral domains, symptoms, and mood that are known to be affected by elemental mercury (Hg degrees ) exposure in human subjects. A behavioral test battery was administered on the day of urine and buccal cell collections for 194 male dentists (DDs) and 233 female dental assistants (DAs) occupationally exposed to Hg degrees for an average of 19 and 10 years, respectively. Subjects had no history of health disorders and were employed for a minimum of 5 years in the dental profession. Respective mean urinary mercury (HgU) levels in DDs and DAs were 3.32 (4.87) microg/l and 1.98 (2.29) microg/l. Corresponding indices of chronic occupational Hg degrees exposure, weighted for historical exposure, were 27.1 (20.6) and 15.2 (12.3). The frequencies of the homogygous common (A/A), heterozygous (A/C), and homozygous polymorphic (C/C) genotypes were 75%, 23% and 2% for DDs and 73%, 25%, and 2% for DAs, respectively. DDs and DAs were evaluated separately. Regression analyses controlled for age, premorbid intelligence, alcohol consumption, and education. Statistically significant associations with HgU (p<0.05) were found for nine measures among DDs (BEES Digit SpanForward and Backward, WMS-R Visual ReproductionN Correct, BEES Symbol DigitRate, BEES Finger TappingDom/Non-dom, and Alternate Partialed, Hand SteadinessFactor1, and BEES Tracking), and eight measures among DAs (BEES Digit SpanForward, BEES Symbol DigitRate, BEES Pattern Discrimination Rate, BEES Trailmaking B, BEES Finger TappingDom/Non-dom, and Alternate Partialed, Hand SteadinessFactor1, and Vibration SensitivityHits). CPOX4 status was associated with four measures in DDs (BEES Spatial SpanForward, BEES Pattern MemoryN Correct, BEES Symbol DigitRate, and BEES VigilanceHit) and five measures in DAs (BEES Digit SpanForward, WMS-R Visual ReproductionsN Correct, BEES Symbol DigitRate, BEES Simple and Choice Reaction TimeMove. Both groups experienced an additive effect (no interaction term) for HgU and the CPOX4 polymorphisms on the DigitRate whereas DAs also had additive effects for BEES Digit SpanForward and for Beck's Depression factor 'Worthlessness'. These exploratory findings suggest that the CPOX4 polymorphism may affect susceptibility for specific neurobehavioral functions associated with mercury exposure in human subjects.
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PMID:The association between a genetic polymorphism of coproporphyrinogen oxidase, dental mercury exposure and neurobehavioral response in humans. 1634 43