PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Aminolevulinic Acid”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1979

The role of zinc with special reference to the essential thiol groups in delta-aminolevulinic acid dehydratase of bovine liver.

delta-Aminolevulinic acid dehydratase (5-aminolevulinic acid hydro-lyase (adding 5-aminolevulinic acid and cyclizing), EC 4.2.1.24 purified from bovine liver in the presence of both SH-reducing reagent and zinc during the purification contained one zinc atom and eight SH groups/subunit. This preparation showed the full enzymatic activity even in the absence of thiol activator. It was found that two cysteine residues, one zinc atom and two histidine residues were involved in the active site. The enzyme was fullly active as long as two SH groups in the active site remained in the reduced form even in the absence of zinc. However, the enzymatic activity was completely lost, with a concomitant loss of bound zinc, upon oxidation of the SH groups to a disulfide bond, modification of SH groups with chemical reagents, or mercaptide formation by heavy metals. Thus, it is apparent that the activity depends on the essential SH groups. The zinc is not absolutely essential for the activity but may be required to prevent the essential SH groups from autooxidation by coordination. Binding experiments indicated that there was one binding site of zinc/subunit. Photooxidation of histidine residues diminished both enzymatic activity and bound zinc, suggesting that the histidine residues not only constituted the active site but also served as a possible ligand to zinc.

Animals↗
PubMed1979

Inherited deficiency of delta-aminolevulinic acid dehydratase.

Delta-aminolevulinic acid dehydratase (ALA-D) is the second enzyme in the porphyrin-heme pathway and converts delta-aminolevulinc acid (ALA) to porphobilinogen (PBG). A family is reported with an inherited deficiency of red cell ALA-D activity occurring over three generations in an autosomal dominant pattern. Intial experiments support the hypothesis that the mutation in this family may affect a regulatory gene, but enzyme purification and further study are required. Although no clinical manifestations of deficient ALA-D activity have been found in affected persons, families such as this may be at increased risk for the serious consequences of lead poisoning, which produces marked inhibition of ALA-D activity.

Adolescent↗
PubMed1979

Study of erythrocyte delta-aminolevulinic acid dehydratase activity in porphyria cutanea tarda.

The erythrocyte delta-aminolevulinic acid dehydratase activity was studied in porphyria cutanea tarda patients, compared to healthy controls, in an attempt to resolve the contradictions in the relevant literature data. In an in vitro experimental system, a study was also made of how the erythrocyte delta-aminolevulinic acid dehydratase activity varies on the action of the activators -SH and Zn2+. It was found that, compared to the healthy controls, the erythrocyte delta-aminolevulinic acid dehydratase activity of porphyria cutanea tarda patients is significantly decreased, but it is restored to the original activity level on the addition of -SH and Zn2+. Since there is a general -SH requirement of delta-aminolevulinic acid dehydratase, the most obvious explanation for the decrease of the activity in the case of the patients is the shift of the natural redox systems of the erythrocytes, and the decrease of the reduced glutathione/oxidized glutathione ratio.

Adult↗
PubMed1979

delta-Aminolevulinic acid synthetase in erythroblasts of patients with pyridoxine-responsive anemia. Hypercatabolism caused by the increased susceptibility to the controlling protease.

Properties of delta-aminolevulinic acid synthetase in erythroblasts of patients with pyridoxine-responsive anemia were investigated with special reference to the protease in mitochondria of erythroblasts. delta-Aminolevulinic acid synthetase activity in erythroblasts of patients with this disease before treatment was extremely decreased, whereas it gradually increased in parallel with the improvement of anemia by the therapy with pyridoxal phosphate. The amount of apo-delta-aminolevulinic acid synthetase in erythroblasts before treatment was also extremely diminished. Apparent affinity to pyridoxal phosphate of the apo-delta-aminolevulinic acid synthetase obtained from erythroblasts of the patients was almost the same as that of normal controls. The activity of a new protease which is considered to be engaged in the regulation of delta-aminolevulinic acid synthetase levels in mitochondria of erythroblasts was shown to be in normal range in erythroblasts of the patients. On the other hand, apo-delta-aminolevulinic acid synthetase obtained from the patients was extremely sensitive to the protease. These results indicate that disturbance of heme synthesis characteristic to pyridoxine-responsive anemia could be ascribed to the hypercatabolism of delta-aminolevulinic acid synthetase caused by the increased susceptibility to the controlling protease in erythroblasts.

5-Aminolevulinate Synthetase↗
PubMed1976

Comparative studies of the effects of cyclic AMP, various hormones and chloramphenicol on the induction of delta-aminolevulinic acid synthetase and tyrosine aminotransferase in the organ-cultured chick embryo liver.

Induction of delta-aminolevulinic acid synthetase by allylisopropylacetamide in organ-cultured chick embryo liver was not appreciably influenced by any of cycli AMP, dibutyryl cyclic AMP, theophylline, glucose, insulin, glucagon, epinephrine, isoproterenol, and hydrocortisone, whereas the activity of tyrosine aminotransferase significantly increased in response to cyclic AMP and some of those hormones. Accumulation of delta-aminolevulinic acid synthetase in the cultured liver cytosol fraction was not appreciably increased by the addition of dibutyryl cyclic AMP or insulin to the incubation medium. Apparently the behaviors of the induction of delta-aminolevulinic acid synthetase in chick embryo liver in ovo and in vitro differ from those in the livers of adult chicken and rat. High concentrations of chloramphenicol suppressed significantly the allylisopropylacetamide-induced increase of delta-aminolevulinic acid synthetase as well as incorporation of 14C-leucine into proteins. The activity of tyrosine aminotransferase, however, was rather increased when relatively low concentrations of chloramphenicol were added to the medium.

5-Aminolevulinate Synthetase↗
PubMed1975

Genetic control of chlorophyll biosynthesis in chlamydomonas: analysis of a mutant affecting synthesis of delta-aminolevulinic acid.

A Mendelian mutation, r-1, in Chlamydomonas reinhardtii has been isolated which elevates protoporphyrin accumulation of the Mendelian protoporphyrin mutants brS-1 and brC-1 more than 20 fold. This increased protoporphyrin accumulation is shown to result from increased delta-aminolevulinic acid synthesis in the double mutants brS-1 r-1 and brC-1 r-1 over that of brS-1 and brC-1 alone. By itself, the r-1 mutation has no detectable protoporphyrin accumulation and has reduced levels of delta-aminolevulinic acid synthesizing activity, chlorophyll, protoheme, and cytochrome oxidase activity. The low levels of chlorophyll and protoheme in r-1 can be increased by feeding delta-aminolevulinic acid. We hypothesize that r-1 may be a mutation of the gene coding for the delta-aminolevulinic acid synthesizing enzyme which reduces the sensitivity of this enzyme to feedback inhibition by protoporphyrin or heme as well as reducing the overall activity of the enzyme. Evidence is also presented for a single delta-aminolevulinic acid synthesizing enzyme serving both chlorophyll and heme biosynthesis.

5-Aminolevulinate Synthetase↗
PubMed1977

[A new method for the clinical determination of urinary porphobilinogen and delta-aminolevulinic acid].

A new method has been developed for clinical determination of porphobilinogen and delta-aminolevulinic acid in urine. Compared with the method of Mauzerall and Granick, being the most commonly used method for clinical application, there is an essential reduction of work and needed time. During the flow of 0.5 ml urine on a 0.7 cm x 2 cm column of macroporous cation exchange resin in H+-form porphobilinogen and delta-aminolevulinic acid are bound to the resin. After rinsing the column with 3 ml N acetic acid and 1 ml H2O the bound hemprecursors were eluted with 5 ml buffer. Concentration of porphobilinogen and of the pyrrol, synthesized from delta-aminolevulinic acid by Knorr-reaction is measured photometrically at 546 nm after Ehrich-reaction. After a short-time regeneration of columns -- 5 ml buffer, 3 ml N acetic acid -- these columns can be reused at least 20 times.

Aminolevulinic Acid↗
PubMed1979

Inhibition of the evoked release of acetylcholine by the porphyrin precursor delta-aminolevulinic acid.

The effect of delta-aminolevulinic acid (ALA) on neuromuscular transmission were studied. High concentrations (0.6 to 18 mM) of ALA caused significant reductions in the amplitudes of curarized end-plate potentials (epps). Changing the ratio of calcium to magnesium in the bathing solution allowed the quantal content of the epps to be directly measured. Under these conditions, ALA reduced the quantal content of epps without affecting the depolarization produced by a single quantum of acetylcholine. It was concluded that ALA, in high concentrations, inhibits the release of acetylcholine evoked by a nerve impulse but is unlikely to be the cause of the neurological defects of acute porphyria.

Acetylcholine↗
PubMed1979

delta-Aminolevulinic acid synthetase from rat liver mitochondria. Purification and properties.

delta-Aminolevulinic acid synthetase has been purified from liver mitochondria of young, uninduced rats. After nonionic detergent solubilization of mitochondrial inner membrane-matrix fractions, the enzyme was purified to a specific activity of approximately 2,000 nmol of delta-aminolevulinic acid formed/h/mg of protein at 30 degrees C, by means of ammonium sulfate precipitation, diethylaminoethyl cellulose chromatography, Sephacryl chromatography, and preparative gel electrophoresis. The purified enzyme preparation thus obtained was apparently homogeneous as judged by its migration as a single band with a molecular weight of 58,000 +/- 6,000 upon electrophoresis in sodium dodecyl sulfate polyacrylamide gels. The native enzyme probably exists as a dimer with a molecular weight of approximately 120,000. A pH optimum of 7.5 and an isoelectric point of 4.5 were also determined. Both monovalent cations and hemin strongly inhibited the activity of the purified enzyme.

5-Aminolevulinate Synthetase↗
PubMed1977

Quaternary structure of delta-aminolevulinic acid synthase from Rhodopseudomonas spheroides.

Delta-Aminolevulinic acid synthase (succinyl-CoA: glycine C-succinyltransferase (decarboxylating) EC 2.3.1.37) was purified from Rhodopseudomonas spheroides. The purity of the enzyme preparation was established by its behavior in disc electrophoresis in the presence and absence of sodium dodecyl sulfate and by analytical ultracentrifugation. The molecular weight of the enzyme as determined by sedimentation equilibrium was found to be about 80,300, a value similar to those obtained by gel filtration, polyacrylamide gel electrophoresis, and sucrose gradient centrifugation. The molecular weight of the enzyme, denatured with either sodium dodecyl sulfate or guanidine hydrochloride, was found to be about 45,000 and 41,000, respectively. The dimeric structure was supported by sedimentation in sucrose gradients. Further evidence for the dimetic nature of the enzyme was obtained by gel electrophoresis of the enzyme treated with dimethylsuberimidate and sodium dodecyl sulfate.

5-Aminolevulinate Synthetase↗
PubMed1975

Regulation of mitochondrial biogenesis: enzymatic changes in cytochrome-deficient yeast mutants requiring delta-aminolevulinic acid.

Yeast cells almost completely deficient in all cytochromes were obtained by introducing two defective nuclear genes, cyd1 and cyc4, into the same haploid strain. The action of the two mutant genes is synergistic, since either gene acting singly results in only partial cytochrome deficiency. Normal synthesis of all cytochromes can be restored in the double mutant by adding delta-aminolevulinic acid to the growth medium. The optimum concentration of delta-aminolevulinate for restoration of cytochrome synthesis is about 40 muM; when higher concentrations are used, synthesis of cytochromes is partially suppressed, particularly that of cytochrome a.a3. Growth yield of the double mutant is stimulated by ergosterol and Tween 80, a source of unsaturated fatty acid. Methionine stimulates further. None of these nutrients is required for growth when sufficient delta-aminolevulinic acid is present in the growth medium. With respect to nutritional responses, the single-gene, cytochrome-deficient mutant, ole3, behaves like the double mutant. The frequency of the p-mutation in the double mutant grown in the absence of ergosterol, Tween 80, and delta-aminolevulinic acid is at least 15%. The frequency can be reduced to less than 1% by either delta-aminolevulinic acid or Tween 80. Ergosterol alone does not decrease the p- frequency. The ole3 mutant does not exhibit increased p-frequency under similar conditions of unsaturated fatty acid deficiency.

5-Aminolevulinate Synthetase↗
PubMed1978

Cellular and molecular toxicology of lead. II. Effect of lead on delta-aminolevulinic acid synthetase of cultured cells.

The effect of lead nitrate on delta-aminolevulinic acid synthetase (ALA synthetase), the first and rate-limiting enzyme of the heme biosynthetic pathway, was studied by using an established rat liver cell line (RLC-GAI). Lead was shown to produce a time-dependent increase in ALA synthetase activity, with a maximum after incubation of the cells for 24 h with 10(-5) M lead nitrate. The effect of lead was not liver-specific in that increases in enzyme activity were produced in other tissue-derived cell lines. Cycloheximide but not actinomycin D, cordycepin, or hydroxyurea, at concentrations that inhibit the synthesis of protein, RNA, and DNA, prevented the lead-associated increase in ALA synthetase activity. Heme, added to the cells as hemin, also prevented the effect of lead. These results indicate that lead induced the synthesis of ALA synthetase secondary to an inhibition of the synthesis of heme.

5-Aminolevulinate Synthetase↗
PubMedDate not supplied

Physical parameters and possible regulation of zeta-aminolevulinic acid synthetase.

Physical measurements were made on the zeta-aminolevulinic acid synthetase from Rhodopseudomonas spheroides. These include a Stokes radius of 3.8 nm, determined by gel filtration, and sedimentation coefficient of 5.46 S by sucrose density gradient centrifugation. From these measurements and the value of partial specific volume of 0.732 ml/g determined from the amino acid composition, the following physical constants were calculated: molecular weight, 88000; diffusion coefficient, 5.65 X 10(-7) cm2s-1; frictional ratio, 1.30; axial ratio, 5.0. The enzyme is inhibited by more than 50% by glyceraldehyde 3-phosphate (1mM), pyruvate (0.02 M), alpha-ketoglutarate (0.02 M), urea (0.8 M), CoCl2 (0.2 mM) and hemin (5 micrograms). The effect of these inhibitors on the possible regulation of this enzymic activity is discussed.

5-Aminolevulinate Synthetase↗
PubMed1979

5-Aminolevulinic acid stimulation of porphyrin and hemoglobin synthesis by uninduced Friend erythroleukemic cells.

Porphyrin synthesis and iron accumulation was stimulated by exogenous 5-aminolevulinic acid (ALA) in uninduced Friend erythroleukemic cells (FELC). Uroporphyrin and protoporphyrin were the major intermediated precursors produced. All porphyrin types were conjugated to protein insoluble cellular components and could be extracted only by methanol sulfuric acid esterification. Heme content of the uninduced FELC was increased 6-fold in the presence of 5 x 10(-4) M ALA. As a consequence, the synthesis of the minor murine hemoglobin component was preferentially induced, an effect similar to that expressed by exogenous hemin. Addition of exogenous ALA to 0.5% DMSO-induced cells increased total hemoglobin synthesis with a higher efficiency of the minor hemoglobin. The endogenous synthesis of porphyrin from exogenous ALA was markedly reduced by hemin. Uroporphyrin, coproporphyrin, protoporphyrin and heme were equally repressed, indicating an inhibitory effect of hemin on ALA dehydrase and urosynthetase activities. In addition, hemin repressed [3H]leucine incorporation into protein by uninduced cells. Incubation of uninduced cells in culture medium without serum in the presence of hemin blocked their protein synthesis activity, whereas addition of serum exerted a protective effect on living FELC.

Aminolevulinic Acid↗
PubMed1977

delta-Aminolevulinic acid: influences on synaptic GABA receptor binding may explain CNS symptoms of porphyria.

Symptoms of acute porphyria have been attributed to effects of delta-aminolevulinic acid (ALA). We report that ALA selectively competes for the binding of tritiated gamma-aminobutyric acid ([3H]GABA) associated with synaptic GABA receptors in central nervous system membranes. Concentrations of ALA that inhibit GABA receptor binding are consistent with levels of ALA thought to exist in the central nervous system of porphyric patients. Some of the symptoms of acute porphyria resemble those elicited by muscimol, a potent GABA agonist drug. Barbiturates, which exacerbate porphyric symptoms, are potent facilitators of the synaptic actions of GABA. The results suggest that some symptoms of acute porphyria might be attributable to a mimicking by ALA of GABA at its central nervous system receptor sites.

Aminolevulinic Acid↗
PubMed1978

The role of vanadium in green plants. IV. Influence on the formation of delta-aminolevulinic acid in Chlorella.

In a series of experiments, it is demonstrated that the trace element vanadium (4.10(-7) g-at/1 as NH4VO3) has a considerable positive influence on the synthesis of delta-aminolevulinic acid(delta-ALA) in the autotrophically growing green alga Chlorella pyrenoidosa, the effect being visible by an enhanced output of the amino acid into the culture medium in presence of levulinic acid (LA). The level of intracellularly accumulated delta-ALA, however, is not changed in presence of the metal. The V-effect on exogenous found delta-ALA is suppressed, when LA is added to the nutrient medium at low pH (pH5), although V-uptake into the algal cells is not disturbed by LA. As demonstrated in culture media with various nitrogen sources (urea, partially hydrolized urea, ammonium salts), the development of the pH during the cultivation time is important for the presentation of the V-effect on delta-ALA. It is suggested that vanadium acts as a catalyst in the conversion of 4,5-dioxovaleric acid to delta-ALA by transamination.

Aminolevulinic Acid↗