Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:2.5.1.61 (porphobilinogen deaminase)
637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In situ hybridization was used to study the effects of hemin on the expression of the oncogenes c-myc, c-fos, and myb, and on the mRNA level of erythroid porphobilinogen deaminase (PBG-D) and alpha-globin in HEL cells during differentiation. The technique was effective in detecting changes in mRNA levels in small numbers of HEL cells. Hemin stimulation of HEL cells results in an early increase in myb and c-myc expression and a decrease in c-fos mRNA, while increased PBG-D and alpha-globin expression is not seen until 8 h after hemin treatment. Blast-like cells display expression of c-myc, alpha-globin and PBG-D, while the more differentiated cells give a positive response to both c-fos and myb. During HEL cell differentiation, the mechanism of hemin stimulation appears to be through the up regulation of myb and c-myc mRNA and down regulation of c-fos. The subsequent expression of PBG-D and alpha-globin may indicate that early increases in protooncogene expression are first required for the normal progression of erythropoiesis to occur.
...
PMID:Early protooncogene expression during hemin-induced differentiation of human erythroleukemic cells. 228 Jun 14

Acute intermittent porphyria (AIP) is due to a defect in porphobilinogen deaminase (PBGD, E.C. 4.1.3.8) inherited as an autosomal dominant trait. Presymptomatic carrier detection is important in order to avoid exposure to factors inducing severe clinical symptoms. Carriers and noncarriers of the AIP gene can be distinguished by linkage analysis using three intragenic RFLPs in AIP families. In the present study, the polymerase chain reaction (PCR) was used to amplify 3.3-kb genomic sequences covering three polymorphic sites. Haplotypes were identified after cleavage of amplified products with three restriction enzymes, showing that the technique can be successfully used for linkage analysis in AIP families.
...
PMID:Haplotyping of the human porphobilinogen deaminase gene in acute intermittent porphyria by polymerase chain reaction. 230 46

The effect of lead on the activity of erythrocyte porphobilinogen deaminase (PBGD) in vivo and in vitro was investigated using blood specimens obtained from controls and lead-exposed workers. When lead nitrate was added to the incubation mixture at a final concentration of 10(-4) M, 83% inhibition of erythrocyte PBGD activity was found. However, in workers occupationally exposed to lead, no inhibition of erythrocyte PBGD activity was detected. This finding indicates that the erythrocyte PBGD test is not useful for evaluating exposure to lead in workers. In addition, the in vitro study confirmed that mercuric chloride strongly inhibits erythrocyte PBGD activity.
...
PMID:Effect of lead on the activity of erythrocyte porphobilinogen deaminase in vivo and in vitro. 230 32

The Dubin-Johnson syndrome (DJS), a hereditary conjugated hyperbilirubinemia, is associated with an impairment of porphyrin metabolism. Total urinary coproporphyrin (CP) excretion and the urinary CP isomer I and III constellation were examined in 15 patients with DJS and 12 unaffected family members, and then compared with 50 unrelated control persons (55 +/- 15 nmol/24 h of total CP: 27 +/- 3% of isomer I; +/- SD). The patients with DJS excreted 80 +/- 7% (+/- SD) of CP isomer I (p less than 0.001). The isomer relation in two young children, 3 and 5 years old, shows an isomer reversal, with isomer I of about 95%. Studies done on four families from our patients with DJS indicate and confirm the autosomal recessive mode of inheritance. Total urinary CP was found to be elevated in subjects with DJS, reaching a mean value of 164 +/- 123 nmol/24 h (upper limit 120 nmol/24 h). Fecal CP isomers I and III were found to be in the usual physiological proportion to each other, but total fecal CP excretion had declined to the lower normal level (10 +/- nmol/g, n = 8). The pathogenetic mechanisms in DJS have not yet been fully worked out. Four possible explanations are currently under discussion: 1. an impaired hepatic excretory function: 2. a uroporphyrinogen III synthase defect; 3. an increase in porphobilinogen deaminase (uroporphyrinogen synthase) activity, or 4. a membrane-associated transport disorder with secondary metabolic changes of the isomer pool and enzyme activities.
...
PMID:Diagnostic and pathogenetic implications of urinary coproporphyrin excretion in the Dubin-Johnson syndrome. 231 40

A child who was grossly malnourished and who showed increased excretion of porphyrin and porphyrin precursor had normal activity of erythrocyte porphobilinogen deaminase (EC 4.3.1.8) and leukocyte protoporphyrinogen oxidase (EC 1.3.3.4). Clinical symptoms, coincident with the excretion of rose-colored urine, were consistent with the diagnosis of an acute porphyria. The disease resolved spontaneously after the withdrawal of carbamazepine and sodium valproate and the commencement of parenteral nutrition with subsequent carbohydrate loading. In addition to normal concentrations of enzyme activities, the patient is unusual in presenting before puberty and in having no family history of porphyria.
...
PMID:Variant acute intermittent porphyria in a child. 233 98

A 114-base-pair promoter fragment of the human porphobilinogen deaminase gene functioned in an erythroid-specific manner in transient transfection experiments. Site-directed mutagenesis of the binding site for the erythroid-specific transcription factor (NF-E1) or an adjacent CACCC motif abolished the promoter activity. Increasing the spacing between these sites progressively reduced promoter activity, but there was no evidence that a critical alignment of the two factors on the DNA helix was required.
...
PMID:Synergy between the NF-E1 erythroid-specific transcription factor and the CACCC factor in the erythroid-specific promoter of the human porphobilinogen deaminase gene. 235 26

Manifest disease symptoms of acute intermittent porphyria may be provoked by several external factors. Latent gene carriers should be identified at an early stage and informed about preventive measures. Porphobilinogen deaminase activity in red blood cells may be used as one indicator of the carrier state. However, there is an overlap of enzyme activity between healthy controls and carriers of the trait. Thus latent gene carriers cannot always be identified. In the present study a recently reported enzyme-linked immunosorbent assay (ELISA) was used to quantify the concentration of the enzyme porphobilinogen deaminase in erythrocytes in 845 individuals belonging to families with acute intermittent porphyria. Using previous available diagnostic methods 417 of them had been diagnosed as gene carriers, 339 as non-carriers, and 89 were of "uncertain" classification. Of those with "uncertain" diagnosis, 19 had a decreased concentration of porphobilinogen deaminase and could thus be diagnosed as gene carriers. However, 70 cases of the 89 were still "uncertain", which underlines the need for further improvement of the diagnostic methods.
...
PMID:Immunological determination of porphobilinogen deaminase as a diagnostic measure in acute intermittent porphyria. 238 Jun 62

There are eight enzymes in the heme biosynthetic pathway and three enzymes in the heme catabolic pathway. Enzymatic defects in heme biosynthesis lead to clinical conditions termed porphyrias. cDNAs for five of the eight enzymes in the heme biosynthetic pathway and two of the three enzymes in the heme catabolic pathway have been cloned and characterized in mammalian cells. At least two enzymes exist as isozymes between erythroid and non-erythroid tissues. One is delta-aminolevulinic acid synthase (ALAS), and the erythroid and hepatic isozymes are coded by two separate genes. The other is porphobilinogen deaminase (PBGD), and both the erythroid and the non-erythroid PBGD mRNA are transcribed from a single PBGD gene by alternate transcription and splicing. There is also a significant tissue-specific control of expression of the uroporphyrinogen decarboxylase gene which is expressed as a unique mRNA in all tissues.
...
PMID:Regulation of the genes for heme pathway enzymes in erythroid and in non-erythroid cells. 240 80

1. Acute intermittent porphyria (AIP) is sometimes termed a 'pharmacogenetic' disease. patients with genetic deficiency of the enzyme porphobilinogen deaminase are liable to develop acute attacks of porphyria if exposed to a variety of drugs. 2. Two patients are reported who had no evidence of deficiency of erythrocyte porphobilinogen deaminase yet developed typical attacks of AIP while on anticonvulsant therapy. 3. Normal activity of erythrocyte porphobilinogen deaminase does not completely exclude porphyria. 4. Acute porphyria should be suspected if clinical deterioration occurs during therapy with anticonvulsants, or other porphyrinogenic drugs, even in the absence of an underlying genetic defect in haem synthesis in peripheral blood cells.
...
PMID:Acute intermittent porphyria in two patients on anticonvulsant therapy and with normal erythrocyte porphobilinogen deaminase activity. 249 68

A previously unrecognized form of dual porphyria has been identified in four patients. One male and one female with acute symptoms were diagnosed as having acute intermittent porphyria (AIP), and two males with cutaneous and acute symptoms were diagnosed as having porphyria cutanea tarda (PCT). Biochemically, the excretion of haem precursors showed a complex constellation, with signs characteristic of both AIP and PCT. In one male, a clinical course with both overt PCT and acute manifestations of AIP was observed. Enzyme studies of haem biosynthesis in erythrocytes revealed a dual deficiency, with decreased activity of both porphobilinogen deaminase, as seen in AIP, and uroporphyrinogen decarboxylase, as seen in PCT. A family study showed that the two disorders do not consistently segregate together. These findings suggest that the dual porphyria reflects a double heterozygous condition of coexistent AIP and PCT genes in the same subject.
...
PMID:New form of dual porphyria: coexistent acute intermittent porphyria and porphyria cutanea tarda. 249 57


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

---