scholarly journals Towards Initial Indications for a Thiol-Based Redox Control of Arabidopsis 5-Aminolevulinic Acid Dehydratase

Antioxidants ◽  
2018 ◽  
Vol 7 (11) ◽  
pp. 152 ◽  
Author(s):  
Daniel Wittmann ◽  
Sigri Kløve ◽  
Peng Wang ◽  
Bernhard Grimm
Keyword(s):  
Aminolevulinic Acid ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Thioredoxin Reductase ◽  
Reducing Power ◽  
Reduced Form ◽  
Redox Control ◽  
In Planta ◽  
Acid Dehydratase ◽  
Reducing Conditions ◽  
Alad Activity

Thiol-based redox control is one of the important posttranslational mechanisms of the tetrapyrrole biosynthesis pathway. Many enzymes of the pathway have been shown to interact with thioredoxin (TRX) and Nicotinamide adenine dinucleotide phosphate (NADPH)-dependent thioredoxin reductase C (NTRC). We examined the redox-dependency of 5-aminolevulinic acid dehydratase (ALAD), which catalyzed the conjugation of two 5-aminolevulinic acid (ALA) molecules to porphobilinogen. ALAD interacted with TRX f, TRX m and NTRC in chloroplasts. Consequently, less ALAD protein accumulated in the trx f1, ntrc and trx f1/ntrc mutants compared to wild-type control resulting in decreased ALAD activity. In a polyacrylamide gel under non-reducing conditions, ALAD monomers turned out to be present in reduced and two oxidized forms. The reduced and oxidized forms of ALAD differed in their catalytic activity. The addition of TRX stimulated ALAD activity. From our results it was concluded that (i) deficiency of the reducing power mainly affected the in planta stability of ALAD; and (ii) the reduced form of ALAD displayed increased enzymatic activity.

scholarly journals Cytoplasmic and Mitochondrial NADPH-Coupled Redox Systems in the Regulation of Aging

Nutrients ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 504 ◽  
Author(s):  
Patrick Bradshaw
Keyword(s):  
Nicotinamide Adenine Dinucleotide ◽  
Aging Process ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Thioredoxin Reductase ◽  
Nicotinamide Adenine ◽  
Model Organisms ◽  
Reduced Form ◽  
Redox Systems ◽  
Redox Stress ◽  
Species Longevity

The reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) protects against redox stress by providing reducing equivalents to antioxidants such as glutathione and thioredoxin. NADPH levels decline with aging in several tissues, but whether this is a major driving force for the aging process has not been well established. Global or neural overexpression of several cytoplasmic enzymes that synthesize NADPH have been shown to extend lifespan in model organisms such as Drosophila suggesting a positive relationship between cytoplasmic NADPH levels and longevity. Mitochondrial NADPH plays an important role in the protection against redox stress and cell death and mitochondrial NADPH-utilizing thioredoxin reductase 2 levels correlate with species longevity in cells from rodents and primates. Mitochondrial NADPH shuttles allow for some NADPH flux between the cytoplasm and mitochondria. Since a decline of nicotinamide adenine dinucleotide (NAD+) is linked with aging and because NADP+ is exclusively synthesized from NAD+ by cytoplasmic and mitochondrial NAD+ kinases, a decline in the cytoplasmic or mitochondrial NADPH pool may also contribute to the aging process. Therefore pro-longevity therapies should aim to maintain the levels of both NAD+ and NADPH in aging tissues.

scholarly journals 5-Aminolevulinic acid dehydratase deficiency porphyria: a twenty-year clinical and biochemical follow-up

1998 ◽  
Vol 44 (9) ◽  
pp. 1892-1896 ◽  
Author(s):  
Ulrich Gross ◽  
Shigeru Sassa ◽  
Karl Jacob ◽  
Jean-Charles Deybach ◽  
Yves Nordmann ◽  
...  
Keyword(s):  
Enzyme Activity ◽  
Reference Values ◽  
Aminolevulinic Acid ◽  
Compound Heterozygous ◽  
Acid Dehydratase ◽  
Heme Arginate ◽  
Alad Activity ◽  
Rate Limiting ◽  
Acute Crisis

Abstract 5-Aminolevulinic acid dehydratase (ALAD) activity in two patients with compound heterozygous 5-aminolevulinic acid dehydratase deficiency porphyria was studied over the last 20 years. The patients’ enzyme activity was <10% from 1977 to 1997. An acute crisis in each patient was successfully treated by infusion of glucose and heme arginate. After this therapy both urinary 5-aminolevulinic acid (ALA) and total porphyrins were diminished to 65% in patient B. In patient H, ALA was decreased to 80%, and total porphyrins were reduced to 15% after treatment with heme arginate and glucose. The patients remained free of symptoms after this therapy. Family studies of patient B showed cross-reactive immunological material (CRIM), in which the maternal mutation is CRIM(+), whereas the paternal mutation is CRIM(−). Incubation of erythrocyte lysates with ALA decreased porphyrin formation, whereas incubation with porphobilinogen produced porphyrin concentrations within reference values in both patients, confirming that ALAD activity is rate-limiting in these cells.

The threshold of the delta-aminolevulinic acid dehydratase (ALAD) activities reduced by lead (Pb) exposure could be 10 μg/dL without modification of ALAD G177C genotypes in Chinese Han Taiwanese.

2018 ◽  
Author(s):  
Chan-Ching Huang ◽  
Te-Yu Liu ◽  
Chen-Cheng Yang ◽  
Chao-Ling Wang ◽  
Su-Shin Lee ◽  
...  
Keyword(s):  
Aminolevulinic Acid ◽  
Lead Level ◽  
Blood Lead ◽  
Additive Models ◽  
P Value ◽  
Health Examination ◽  
Chinese Han ◽  
Acid Dehydratase ◽  
Alad Activity ◽  
Lead Workers

Background: Lead inhibits the enzymes in the heme biosynthesis, mainly the δ-aminolevulinic acid dehydratase (ALAD) activities. The aims of this study was to establish ALAD activity assay in Taiwan and analyzed the effects of lead exposure on hematological system and the ALAD activity with the modification of the ALAD genotypes. Methods: Among 121 lead workers and 117 non-exposed workers, the data were from health examination. ALAD activity was determined by the standardized method of the European Community. ALAD genotyping was using a method of PCR-RFLP. For finding a threshold effect, we used generalized additive models (GAM) and scatter plots with smoothing curve, in addition to multiple regression methods. Results: There were 229 ALAD1-1 homozygotes, 9 ALAD1-2 heterozygotes were identified, and none of ALAD2-2 homozygote. Lead workers had significantly lower ALAD activity than non-exposed group (41.6 ± 22.1 vs. 63.3 ± 14.0 U/L, p-value < 0.001). The results of multiple regressions showed the blood lead level (BLL) was profound factor associated with ALAD activity inversely. The possible threshold of BLL affecting ALAD activity was around 10 μg/dL. Conclusions: ALAD activity was inhibited by blood lead, which could be a threshold of 10 ug/dL, which ALAD activity may be adopted as a biomarker of health examination for lead workers.

scholarly journals Inhibition of δ-aminolevulinic acid dehydratase activity by cadmium in excised etiolated maize leaf segments during greening

2011 ◽  
Vol 57 (No. 7) ◽  
pp. 332-337 ◽  
Author(s):  
J. Sarangthem ◽  
M. Jain ◽  
R. Gadre
Keyword(s):  
Enzyme Activity ◽  
Aminolevulinic Acid ◽  
Substantial Reduction ◽  
Competitive Inhibitor ◽  
Cd Accumulation ◽  
Nitrogenous Compounds ◽  
Acid Dehydratase ◽  
Alad Activity ◽  
Maize Leaves ◽  
Dehydratase Activity

Supply of 0.1&ndash;0.5 mmol CdCl<sub>2</sub> inhibited &delta;-aminolevulinic acid dehydratase (EC 4.2.1.24, ALAD) activity and total chlorophylls in excised etiolated segments of maize leaves during greening. Due to cadmium supply &delta;-aminolevulinic acid (ALA) content was reduced significantly at 0.5 mmol Cd only. Also the Cd treatment decreased the protein content and accumulated significantly the Cd in the tissue. Significant correlation between Cd accumulation in the leaves and various parameters measured is observed, with the R-squared values being 0.727 with ALAD activity, 0.885 with ALA content, 0.902 with total chlorophylls and 1.00 with proteins. The % inhibition of ALAD activity by Cd was decreased in the presence of nitrogenous compounds, glutamine and NH<sub>4</sub>NO<sub>3</sub> and the observed inhibition was 25% and 16%, respectively. More substantial reduction in % inhibition of enzyme activity by Cd was observed during treatment with glutathione, a ubiquitous thiol and levulinic acid, a competitive inhibitor of ALAD, with the inhibition being only 2% and 4%, respectively. Supply of some essential metal ions, such as Mg, Zn, and Mn, also reduced the % inhibition of enzyme activity by Cd. Inclusion of varying concentrations of ALA during assay also affected the % inhibition of enzyme activity by Cd showing an increased inhibition from 17% to 53% with increasing ALA concentration. It is suggested that Cd inhibits ALAD activity by affecting the ALA binding to the enzyme and/or disrupting thiol interaction.

scholarly journals Use of Generalized Additive Model to Detect the Threshold of δ-Aminolevulinic Acid Dehydratase Activity Reduced by Lead Exposure

2020 ◽  
Vol 17 (16) ◽  
pp. 5712
Author(s):  
Chan-Ching Huang ◽  
Chen-Cheng Yang ◽  
Te-Yu Liu ◽  
Chia-Yen Dai ◽  
Chao-Ling Wang ◽  
...  
Keyword(s):  
Lead Exposure ◽  
Aminolevulinic Acid ◽  
Lead Level ◽  
Blood Lead ◽  
Additive Models ◽  
Acid Dehydratase ◽  
Alad Activity ◽  
Exposed Workers ◽  
Lead Workers ◽  
Dehydratase Activity

Background: Lead inhibits the enzymes in heme biosynthesis, mainly reducing δ-aminolevulinic acid dehydratase (ALAD) activity, which could be an available biomarker. The aim of this study was to detect the threshold of δ-aminolevulinic acid dehydratase activity reduced by lead exposure. Methods: We collected data on 121 lead workers and 117 non-exposed workers when annual health examinations were performed. ALAD activity was determined by the standardized method of the European Community. ALAD G177C (rs1800435) genotyping was conducted using the polymerase chain reaction and restricted fragment length polymorphism (PCR-RFLP) method. In order to find a threshold effect, we used generalized additive models (GAMs) and scatter plots with smoothing curves, in addition to multiple regression methods. Results: There were 229 ALAD1-1 homozygotes and 9 ALAD1-2 heterozygotes identified, and no ALAD2-2 homozygotes. Lead workers had significantly lower ALAD activity than non-exposed workers (41.6 ± 22.1 vs. 63.3 ± 14.0 U/L, p < 0.001). The results of multiple regressions showed that the blood lead level (BLL) was an important factor inversely associated with ALAD activity. The possible threshold of BLL affecting ALAD activity was around 5 μg/dL. Conclusions: ALAD activity was inhibited by blood lead at a possible threshold of 5 μg/dL, which suggests that ALAD activity could be used as an indicator for lead exposure regulation.

Sign in / Sign up

Export Citation Format

Share Document