Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.5.1.4 (deaminase)
 5,113 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Numerous porphyrin auxotrophic mutants have been isolated from the 168 trpC2 strain of Bacillus subtilis by selection with streptomycin. Some of them could be supplemented with ALA while the majority grew only in the presence of haemin. Among the latter strains, the syntropism test allowed to distinguish two groups different in phenotype, viz., feeders accumulating ALA and non-feeders accumulating instead of ALA other porphyrin intermediates. On the basis of transductional studies, feeders and non-feeders could be divided into two and four groups, respectively. Biochemical investigation revealed that, with one exception, one enzyme of the porphyrin biosynthesis was coordinated to each hem locus. The following genes were identified:hemB yields ALA-dehydrase;hemC yields PBG-deaminase; hemE yields uroporphyrinogen decarboxylases; hemF yields coproporphyrinogen oxidase; hemG yields protoporphyrin-iron-chelatase.
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PMID:Genetic and biochemical analysis of haemin dependent mutants of Bacillus subtilis. 80 3

1. The effect of enflurane, a volatile anesthetic, on heme metabolism was studied. Different doses (0.5-6.0 ml/kg) of this anesthetic were administered i.p. to mice and animals sacrificed at different times after administration (5-240 min). 2. The dose of 2 ml/kg was chosen as the optimum anesthetic dose producing more alterations in the heme pathway. 3. ALA-S was significantly induced at earlier times of anesthesia. 4. Blood PBGase and deaminase was greatly reduced. 5. This diminution coupled with ALA-S induction are in accordance with the known biochemical changes occurring in acute intermittent porphyria and include enflurane in the list of porphyrinogenic drugs, the use of which is not recommended for the management of anesthesia in porphyric patients.
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PMID:Porphyrinogenic properties of the anesthetic enflurane. 139 73

1. delta-Aminolevulinic acid dehydratase (ALA-D), blood lead and several enzymes and metabolites of the heme biosynthetic pathway were measured in a number of symptomatic porphyric patients, 22 with acute intermittent porphyria, three with hereditary hepatic coproporphyria, 10 with hereditary porphyria cutanea tarda, two with erythropoietic protoporphyria and two with congenital erythropoietic porphyria and in 84 lead intoxicated persons. 2. In the 39 individuals suffering from the inherited porphyrias and in 32 lead poisoned patients with a 30-50% reduced deaminase, blood lead content was not sufficiently increased (average 28 micrograms%) to account for the greatly decreased activity of ALA-D (average 36% of controls). 3. After a relatively trifling lead exposure they developed the signs of acute lead intoxication. 4. A second group of lead intoxicated patients showing low ALA-D activity and corresponding high concentration of lead in blood, exhibited no other physiologic deviation in the enzymes and metabolites of porphyrin biosynthesis. 5. Individuals with inherited porphyrias are ultrasensitive to low level lead exposure and that lead would also act as a triggering factor. In these patients, lead intoxication can be considered a toxogenetic disorder. 6. An inversely linear correlation between ALA-D activity and blood lead content was obtained for both groups of lead intoxicated patients, however, a different constant (k) for each was obtained, which we have taken as a measure of lead toxogeneticity: k = 10 +/- 1 for lead intoxicated individuals with otherwise normal heme metabolism and k = 5 +/- 0.5 for lead intoxicated symptomatic porphyric patients. 7. Determination of erythrocytic ALA-D, besides blood lead, will be a valuable indicator for preventive medical care for these patients, when they are expected to be exposed to lead either environmentally or in their professional life.
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PMID:In inherited porphyrias, lead intoxication is a toxogenetic disorder. 362 5

The heat-stable polypeptide ATP-dependent proteolysis factor 1 (APF-1) of the reticulocyte proteolytic system forms covalent compounds with proteins in an ATP-requiring reaction. APF-1 and lysozyme, a good substrate for ATP-dependent proteolysis, form multiple conjugates, as was shown by comigration of label from each upon gel electrophoresis. Multiple bands were also seen with other substrates of the ATP-dependent proteolytic system, such as globin or alpha-lactalbumin. Analysis of the ratio of APF-1 to lysozyme radioactivities and of the molecular weights of the bands indicated that they consist of increasing numbers of the APF-1 polypeptide bound to one molecule of lysozyme. The covalent linkage is probably of an isopeptide nature, because it is stable to hydroxylamine and alkali, and polylysine is able to give conjugates of APF-1. Removal of ATP after formation of the 125I-labeled APF-1 conjugates with endogenous proteins caused the regeneration of APF-1, indicating presence of an amidase. This reaction is thought to compete with proteases that may act on APF-1-protein conjugates, especially those containing several APF-1 ligands. A sequence of reactions in which the linkage of APF-1 to the substrate is followed by the proteolytic breakdown of the substrate is proposed to explain the role of ATP.
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PMID:Proposed role of ATP in protein breakdown: conjugation of protein with multiple chains of the polypeptide of ATP-dependent proteolysis. 699 Apr 14

1. The effect of enflurane or isoflurane anesthesia (1 ml/kg, i.p.) in animals chronically treated with ethanol (30%, v/v, in drinking water during a week) on heme metabolism and its regulation was investigated. 2. In those animals previously intoxicated with ethanol that received isoflurane, ALA-S activity was increased (control values: 0.071 +/- 0.022 nmol/mg, n = 10; treated animals: 0.110 +/- 0.034 nmol/mg, n = 8) and blood PBGase and deaminase were strikingly diminished (control values, n = 10: PBGase: 0.101 +/- 0.015 nmol/mg, deaminase: 0.242 +/- 0.075 nmol/mg; treated animals, n = 6: PBGase: 0.063 +/- 0.013 nmol/mg; deaminase: 0.145 +/- 0.045 nmol/mg). 3. The time-response study showed that liver ALA-S is enhanced at shorter times of anesthesia with isoflurane and that blood PBGase and deaminase appeared inhibited later in animals previously treated with ethanol. 4. Results reproduce some biochemical alterations known to occur in acute intermittent porphyria.
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PMID:Alterations in fluorinated ether anesthetics effects on heme metabolism following chronic ethanol consumption. 759 Jan 42

A frequent coexistence of diabetes and porphyria disease has been reported. Under normal conditions, porphyrin biosynthesis is well regulated to only form the amount of heme required for the synthesis of the various hemoproteins. The activity of some heme enzymes and rhodanese in streptozotocin (STZ) induced diabetic mice and in allylisopropylacetamide (AIA) induced experimental acute porphyria mice has been examined. The role of alpha-tocopherol (alpha-T), reported to prevent protein glycation in vitro, has also been investigated. AIA induced hepatic delta-aminolevulinic acid synthetase (ALA-S) activity in control animals but was ineffective in the diabetic group. alpha-Tocopherol did not modify ALA-S activity in either group. delta-Aminolevulinic acid dehydratase (ALA-D) and deaminase activities were significantly diminished both in liver and blood of diabetic animals. alpha-Tocopherol prevented inhibition of ALA-D, deaminase and blood rhodanese activities in diabetic animals but alpha-tocopherol by itself did not affect the basal levels of the enzymes studied. The potential use of alpha-tocopherol to prevent late complications of diabetes, including the onset of a porphyria like syndrome is considered.
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PMID:STZ-induced diabetes in mice and heme pathway enzymes. Effect of allylisopropylacetamide and alpha-tocopherol. 772 1

1. The effect of the administration of several doses of Enflurane and Isoflurane (2 ml/kg, i.p., daily) on heme metabolism and glucose levels was studied. 2. Liver and kidney delta-Aminolevulinic acid synthetase (ALA-S) activities were 85% (P < 0.01) induced after the third dose of Enflurane, instead induction of this enzyme was only detected, in animals receiving one dose of Isoflurane. 3. Blood Porphobilinogenase and deaminase (50%, P < 0.01) inhibition was produced only when animals received a single dose of the anesthetics. 5. ALA-S induction observed after the third dose of anesthetics could be a consequence of long lasting depletion in heme synthesis produced by blocking at uroporphyrinogen level.
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PMID:Effect of multiple doses of volatile anesthetics on heme enzymes. 787 42

1. The effect of URO I on the activity of ALA-D, PBGase, deaminase and URO-D, both in aerobiosis and anaerobiosis, was studied. 2. Photoinactivation of the enzymes was much lower in an anaerobic than in an aerobic atmosphere. 3. Dark inactivation in the absence of oxygen was lower than its presence. 4. Preincubation in the presence of ALA or PBG protected the enzymic activity of ALA-D, PBGase and deaminase against URO I-inactivation both under u.v. light and in the dark. 5. Photoinactivating action of URO I would be mediated by reactive oxygen species generated by the excited porphyrin after its absorption of light. Dark inactivation, in aerobiosis, can also be partly mediated by amino acid oxidation, although to a lesser extent than that observed under u.v. light.
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PMID:How the atmosphere and the presence of substrate affect the photo and non-photoinactivation of heme enzymes by uroporphyrin I. 817 60

1. The influence of strain and sex on the effect of enflurane and isoflurane and administration on heme metabolism was investigated to identify the animal model which could best reproduce the biochemical signs of acute intermittent porphyria. 2. Enflurane produced 35% and 80% increases in ALA-S activity only in CF1 male and female mice, respectively, whereas isoflurane induced 40% enzyme activity in CF1 male. 3. CF1 males showed around 35% decrease in blood PBGase and PBG-deaminase after administration of enflurane, whereas isoflurane provoked a striking inhibition (70%) in males of the C57 strain. 4. Enflurane produced alterations in heme synthesis, which would fit a model of acute porphyria in CF1 male mice. On the other hand, isoflurane would mimic biochemical alterations of this porphyria in C57 males.
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PMID:Strain and sex differences in the effect of enflurane and isoflurane on heme metabolism in mice. 890 83

Amiodarone (AD) is an effective antidysrythmic drug, however, there can be serious side effects, such as hepatic and neurological alterations, as well as skin photosensitization, as seen in porphyrias. Clinical signs in porphyrias might be triggered by the so-called porphyrinogenic drugs. Without sound basis, Amiodarone has been classified as an unsafe drug for porphyric patients. The aim of this work has been to study the effect of AD, both in vivo and in vitro, on heme metabolism. In the in vivo assays, the activities of 5-aminolevulinate synthetase (ALA-S), ALA dehydratase (ALA-D), porphobilinogenase (PBGase) and PBG-deaminase (PBG-D) in blood, liver, and kidney; hepatic and fecal porphyrins, urinary ALA, PBG and porphyrins in male mice strain CF1 treated with AD (100 mg i.p. daily) for 1 week and 1 month, were measured. No significanat differences were found for any of these parameters in the AD treated animals as compared to controls. In the in vitro experiments human blood, and mice blood, liver, and kidney, were used to measure the activities of ALA-S, ALA-D, PBGase, PBG-D and uroporphyrinogen decarboxylase, in the presence of varying concentrations of AD (0.0172-4.304 mM). AD did not modify any of the enzyme activities. All of the above biochemical parameters were studied in 17 cardiac patients under AD treatment for 3 to 20 years. Neither the activities of the heme enzymes, nor the levels of precursors and porphyrins in urine and plasma were altered. These findings clearly demonstrate that AD is a pharmacologically safe drug and can be used for the treatment of associated pathologies in porphyrias.
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PMID:Amiodarone is a pharmacologically safe drug for porphyrias. 1018 29


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