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:3.5.1.4 (deaminase)
5,113 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Highly stable labelled complexes are formed between porphobilinogen deaminase and stoicheiometric amounts of [14C]porphobilinogen. On completion of the catalytic cycle by the addition of excess of substrate, the complexes yield labelled product and display all the properties expected from covalently bound enzyme intermediates involved in the deaminase catalytic sequence.
...
PMID:Mechanism of action of porphobilinogen deaminase. The participation of stable enzyme substrate covalent intermediates between porphobilinogen and the porphobilinogen deaminase from Rhodopseudomonas spheroides. 697 21

The activity of uroporphyrinogen III cosynthetase may be determined in a direct assay system in which preuroporphyrinogen is generated from porphobilinogen by the action of porphobilinogen deaminase. The basis of the assay relies on the much faster enzymatic conversion of preuroporphyrinogen into uroporphyrinogen III by cosynthetase compared with the non-enzymic decomposition of preuroporphyrinogen into uroporphyrinogen I. The amount of porphyrinogen (measured as porphyrins) formed from porphobilinogen in the presence of the cosynthetase, after subtraction of the porphyrin formed with deaminase alone, gives a direct assessment of the uroporphyrinogen III and therefore of the cosynthetase activity. The assay may be utilized for the determination of pure cosynthetases and for cosynthetases in crude systems such as whole blood haemolysates or liver homogenates. The assay can be accomplished in a fraction of the time required for previous methods.
...
PMID:Uroporphyrinogen III cosynthetase: a direct assay method. 714 Jul 18

Porphobilinogen is the substrate of two enzymes: porphobilinogen deaminase and porphobilinogen-oxygenase. The first one transforms it into the metabolic precursors of heme and the second diverts it from this metabolic pathway by oxidizing porphobilinogen to 5-oxopyrrolinones. Rat blood is devoid of porphobilinogen-oxygenase under normal conditions while it carries porphobilinogen-deaminase activity. When the rats were submitted to hypoxia (pO2 = 0.42 atm) for 18 days, the activity of porphobilinogen-oxygenase appeared at the tenth day of hypoxia and reached the maximum at the 14-16th day. It decreased to a half after 2 days (half-life of the enzyme) and disappeared after 4 days of return to normal oxygen pressure. Porphobilinogen-deaminase activity increased after the first day of hypoxia, reached a maximum at the 14-16th day and did not decrease to normal values until the 15th day after return to normal oxygen pressure. The activities of both porphobilinogen-oxygenase and porphobilinogen-deaminase were induced by administration of erythropoietin. When rats were made anaemic with phenylhydrazine, porphobilinogen-oxygenase activity also appeared in the blood cells. Although the reticulocyte concentration was higher when compared to that obtained under hypoxia, the activities of the oxygenase obtained under both conditions were comparable. Porphobilinogen-deaminase activity was always closely related to the reticulocyte content. The appearance of porphobilinogenase-oxygenase under the described erythropoietic conditions was due to a de novo induction of the enzyme, as shown by its inhibition with actinomycin D and cycloheximide. Porphobilinogen-oxygenase as well as porphobilinogen-deaminase were present in the rat bone marrow under normal conditions. Their activities increased in phenylhydrazine treated rats. The properties and kinetics of porphobilinogen-oxygenase from the rat blood and bone marrow were determined and found it differ in several aspects.
...
PMID:Induction of porphobilinogen oxygenase and porphobilinogen deaminase in rat blood under conditions of erythropoietic stress. 726 Jan 10

Porphobilinogen deaminase (hydroxymethylbilane synthase) and uroporphyrinogen III synthase (uroporphyrinogen III cosynthase) catalyze the transformation of four molecules of porphobilinogen, via the 1-hydroxymethylbilane, preuroporphyrinogen, into uroporphyrinogen III. A combination of studies involving protein chemistry, molecular biology, site-directed mutagenesis, and the use of chemically synthesized substrate analogs and inhibitors is helping to unravel the complex mechanisms by which the two enzymes function. The determination of the X-ray structure of E. coli porphobilinogen deaminase at 1.76 A resolution has provided the springboard for the design of further experiments to elucidate the precise mechanism for the assembly of both the dipyrromethane cofactor and the tetrapyrrole chain. The human deaminase structure has been modeled from the E. coli structure and has led to a molecular explanation for the disease acute intermittent porphyria. Molecular modeling has also been employed to stimulate the spiro-mechanism of uroporphyrinogen III synthase.
...
PMID:Porphobilinogen deaminase and uroporphyrinogen III synthase: structure, molecular biology, and mechanism. 759 65

Porphobilinogen deaminase from Escherichia coli becomes progressively more susceptible to inactivation by the thiophilic reagent N-ethylmaleimide (NEM) as the catalytic cycle proceeds through the enzyme-intermediate complexes ES, ES2, ES3, and ES4. Site-directed mutagenesis of potentially reactive cysteines has been used to identify cysteine-134 as the key residue that becomes modified by the reagent and leads to inactivation. Since cysteine-134 is buried at the interface between domains 2 and 3 of the E. coli deaminase molecule, the observations suggest that a stepwise conformational change occurs between these domains during each stage of tetrapyrrole assembly. Interestingly, mutation of the invariant active-site cysteine-242 to serine leads to an enzyme with up to a third of the catalytic activity found in the wild-type enzyme. Electrospray mass spectrometry indicates that serine can substitute for cysteine as the dipyrromethane cofactor attachment site.
...
PMID:Evidence for conformational changes in Escherichia coli porphobilinogen deaminase during stepwise pyrrole chain elongation monitored by increased reactivity of cysteine-134 to alkylation by N-ethylmaleimide. 766 87

The biosynthesis of the uroporphyrinogen III macrocycle from porphobilinogen requires the sequential participation of two enzymes--porphobilinogen deaminase (1-hydroxymethylbilane synthase, EC 4.3.1.8) and uroporphyrinogen III synthase (cosynthase, EC 4.2.1.75). The product of the deaminase-catalysed reaction is a highly unstable 1-hydroxymethylbilane called preuroporphyrinogen which acts as the substrate for the uroporphyrinogen III synthase, resulting in the exclusive formation of uroporphyrinogen III. In the absence of the synthase, preuroporphyrinogen cyclizes spontaneously to give uroporphyrinogen I. Porphobilinogen deaminase contains a dipyrromethane cofactor that acts as a primer onto which the tetrapyrrole chain is built. The assembly process occurs in stages through enzyme-intermediate complexes, ES, ES2, ES3 and ES4. The negatively charged carboxylates of the cofactor, substrate and intermediate complexes interact with positively charged amino acid side chains in the catalytic cleft. Mutagenesis of conserved arginines has dramatic effects on the assembly of the dipyrromethane cofactor and on the tetrapolymerization process. During the polymerization, the enzyme changes conformation to accommodate the elongating pyrrole chain. The structure of the deaminase from Escherichia coli has been determined by X-ray crystallography at 1.9A resolution and gives important insight into the enzymic mechanism. Aspartate 84 plays a key role in catalysis and its substitution by glutamate reduces kcat by two orders of magnitude.
...
PMID:The biosynthesis of uroporphyrinogen III: mechanism of action of porphobilinogen deaminase. 784 63

Porphobilinogen deaminase (EC 4.3.1.8) has been purified to homogeneity (16,000-fold) from the plant Arabidopsis thaliana in yields of 8%. The deaminase is a monomer of M(r) 35,000, as shown by SDS/PAGE, and 31,000, using gel-filtration chromatography. The pure enzyme has a Vmax. of 4.5 mumol/h per mg and a Km of 17 +/- 4 microM. Determination of the pI and pH optimum revealed values of 5.2 and 8.0 respectively. The sequence of the N-terminus was found to be NH2-XVAVEQKTRTAI. The deaminase is heat-stable up to 70 degrees C and is inhibited by NH3 and hydroxylamine. The enzyme is inactivated by arginine-, histidine- and lysine-specific reagents. Incubation with the substrate analogue and suicide inhibitor, 2-bromoporphobilinogen, results in chain termination and in inactivation.
...
PMID:Purification and properties of porphobilinogen deaminase from Arabidopsis thaliana. 819 81

The assembly process of the dipyrromethane cofactor of Escherichia coli porphobilinogen deaminase holoenzyme is initiated by the reaction of the porphobilinogen deaminase apoenzyme with preuroporphyrinogen. The resulting enzyme-bound tetrapyrrole (bilane) is equivalent to the holoenzyme intermediate complex ES2 and yields the dipyrromethane cofactor by reactions of the normal catalytic cycle. These observations indicate that preuroporphyrinogen, rather than porphobilinogen, is the preferred precursor for the dipyrromethane cofactor and explain the existence of the D84A and D84N deaminase mutants as catalytically inactive ES2 complexes.
...
PMID:Discovery that the assembly of the dipyrromethane cofactor of porphobilinogen deaminase holoenzyme proceeds initially by the reaction of preuroporphyrinogen with the apoenzyme. 868 74

Acute intermittent porphyria is an autosomal dominant condition caused by a genetic defect of the deaminase gene located on the 11. chromosome. Due to this defect only 50% of the normal enzyme quantity is produced. The disease becomes manifested only in the case of increased demands on given metabolic pathway resulting in porphobilinogen accumulation and storage in the organism. Clinical pattern involves abdominal, neurologic and psychiatric symptomatology. Laboratory diagnosis is based on the detection of delta-aminolevulinic acid, porphobilinogen, uroporphyrin and coproporphyrin in the urine. Between the attacks may only the detection of porphobilinogen deaminase in erythrocytes, leukocytes and skin fibroblasts be positive. The therapy is based on infusions of 20% glucose solution and hydromineral imbalance correction. When neurologic symptoms occur it is necessary to administer hem-arginate intravenously. The case report presents almost textbook case of a young female patient suffering from the disease. (Ref. 7.)
...
PMID:[Acute intermittent porphyria]. 991 55

The activity of porphobilinogen deaminase was measured in young and senescent or mature leaves of pepper (Capsicum annuum), and poinsettia (Euphorbia pulcherrima). Whereas high activity was found in the crude extracts of the young leaves, almost no activity was found in the extracts of senescent or mature leaves. The decrease in deaminase activity was not due to the presence of an isolatable inhibitor. By purifying the crude enzyme extracts from leaves of different ages on DEAE-cellulose columns it was shown that the decrease in deaminase activity was due to a real decrease in the amount of enzyme. Fruiting also decreased porphobilinogen deaminase activity. Several kinetic constants of the C. annuum deaminase were determined.
...
PMID:Disappearance of porphobilinogen deaminase activity in leaves before the onset of senescence. 1666 Aug 74


<< Previous 1 2 3 Next >>

---