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1.
Biol Trace Elem Res ; 200(2): 447-457, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33723800

RESUMO

Delta-aminolevulinic acid dehydratase (ALAD) enzyme catalyzes the second phase of the heme biosynthesis and is involved in lead toxicokinetics. This research aimed to evaluate its influence on the relationship between blood lead (PbB) levels and intellectual performance in Afro-Brazilian children. PbB, hemoglobin concentration, ALAD activity, and polymorphism were determined in whole blood. Anthropometric, socioeconomic, and family environment stimuli data were collected with appropriate instruments. The non-verbal intelligence of children and their mothers or guardians was assessed using the correspondent Raven's Progressive Matrix versions. The medians (range) of PbB levels and ALAD activity were 1.0 µg/dL (0.1-21.3) and, 71 U/L (31-113), respectively. ALAD G177C was distributed as follows: 97.9% for ALAD1/1 and 2.1% for ALAD1/2 genotypes. The mean of Raven raw score was 19.3 (± 5.6) points and there were no differences according to sex or environmental Pb exposure. No statistically significant association was observed between PbB level and children's IQ. However, ALAD activity presented an inverse significant association with PbB levels, children's percentile IQ, and children's IQ/Age ratio, suggesting a neuroprotective role of ALAD1 genotype in those with low PbB level.


Assuntos
Inteligência , Chumbo , Sintase do Porfobilinogênio , Fatores Sociais , Brasil , Criança , Exposição Ambiental , Etnicidade , Genótipo , Humanos , Chumbo/sangue , Sintase do Porfobilinogênio/genética
2.
Artigo em Inglês | MEDLINE | ID: mdl-34444495

RESUMO

Genetic polymorphisms involved in mercury toxicokinetics and toxicodynamics may be associated with severe mercury toxicity. This study aimed to investigate the impact of an ALAD polymorphism on chronic mercury exposure and the health situation of indigenous children from the Brazilian Amazon. One-hundred-and-three indigenous children (under 15 years old) were included and genotyped (rs1800435) using a TaqMan validated assay. The mean age was 6.6 ± 4.5 years old, 60% were female, 49% presented with anemia, and the mean hair mercury concentration was 7.0 ± 4.5 (1.4-23.9) µg/g, with 49% exceeding the reference limit (≥6.0 µg/g). Only two children were heterozygous ALAD, while the others were all wild type. Minor allele frequency (ALAD G) and heterozygous genotype (ALAD CG) were 1% and 2%, respectively. The two children (12 and 14 years old) with the ALAD polymorphism had mercury levels above the average as well as had neurological symptoms related to chronic mercury exposure, such as visual field alterations, memory deficit, distal neuropathy, and toe amyotrophy. Both children also reported frequent consumption of fish in the diet, at least three times a week. In conclusion, our data confirm that an ALAD polymorphism can contribute to mercury half-life time, harmful effects, and neuropsychological disorders in indigenous children with chronic mercury exposure to gold mining activity.


Assuntos
Mercúrio , Sintase do Porfobilinogênio , Animais , Criança , Pré-Escolar , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Polimorfismo Genético , Sintase do Porfobilinogênio/genética
3.
Environ Res ; 170: 65-72, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30557693

RESUMO

OBJECTIVES: Lead exposure is associated with children's growth, but this relationship may depend on the presence of susceptibility factors, including genetic variation. Blood lead levels (BLL) differ by ALAD (aminolevulinic acid dehydratase) genotype. We investigated the association between BLL and growth in Mexican first-graders with different ALAD genotypes. METHODS: Children between the ages of 6-8 years (n = 602) attending first grade in schools within the vicinity of a metal foundry in Torreón, Mexico were enrolled into a randomized controlled trial (RCT) testing the efficacy of iron and/or zinc supplementation on blood lead levels (BLL) and cognition. BLL and anthropometry were assessed at baseline (height, height-for-age z-score (HAZ), knee height, head circumference), after 6 (head circumference) and 12 months (height, HAZ, knee height). Children with ALAD1-1 and ALAD1-2/2-2 were compared. The study sample included 538 and 470 participants who had complete data at baseline and follow-up, respectively. Separate multivariable linear regression models adjusted for covariates were used to test the association between BLL at baseline and each anthropometric measure. Covariates included age, sex, hemoglobin, crowding, and maternal education. BLL x ALAD genotype interaction term was tested. RESULTS: Median BLL (10.1 µg/dL) did not differ by ALAD genotype. After covariate adjustment, baseline BLL was inversely associated with baseline height, HAZ, and knee height. The association (ß [95% CI]) between BLL and baseline height (-0.38[-0.68, -0.09]), HAZ (-0.07[-0.12, -0.02]) and knee height (-0.14[-0.25, -0.02]), was somewhat stronger in children with ALAD1-2/2-2 than ALAD1-1 (-0.09[-0.16, -0.02], -0.02[-0.03, -0.004] and -0.04[-0.06, -0.01], respectively). No associations between BLL and growth at 6 or 12 months were detected irrespective of ALAD genotype. CONCLUSIONS: BLL was adversely associated with anthropometric measures among Mexican children. ALAD genotype may be a susceptibility factor for the effects of lead on child growth.


Assuntos
Antropometria , Exposição Ambiental/estatística & dados numéricos , Chumbo , Sintase do Porfobilinogênio/genética , Criança , Genótipo , Humanos , México
4.
J Toxicol Environ Health A ; 78(16): 1073-81, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26275098

RESUMO

Lead (Pb) is a toxic metal that is widely used by metallurgical industries such as car battery recycling. Exposure to the metal may modify the redox status of the cells and consequently result in changes in activities of important enzymes such as delta-aminolevulinic acid dehydratase (ALAD) and glutathione peroxidase (GPx). Similarly, genetic polymorphisms may modulate the activities of enzymes related to detoxification processes of the metal and may modify Pb body burden. Therefore, the aims of the present study were (i) to evaluate the correlation between blood lead levels (BLL) and activities of the enzymes ALAD and GPx, and (ii) to determine whether activities of these enzymes may be influenced by polymorphisms in ALAD and GPx genes in Brazilian automotive battery workers chronically exposed to Pb, as well as the effects of these polymorphisms on BLL. Our study included 257 participants; BLL were determined by inductively couple plasma-mass spectrometry (ICP-MS), and the activities of the enzymes ALAD and GPx were quantified spectrophotometrically; and genotyping of ALAD (rs1800435) and GPx-1 (rs1800668) polymorphisms was performed by TaqMan assays (real-time polymerase chain reaction, RT-PCR). Significant negative correlations were found between BLL and ALAD activity. Subjects who carried at least one polymorphic allele for ALAD gene displayed markedly lower ALAD activities, while no significant effect was observed regarding GPx-1 polymorphism and activity of the same enzyme. Further, ALAD and GPx-1 polymorphisms exerted no marked influence on BLL. Taken together, our results showed that BLL affected ALAD but not GPx activities, and these were not modulated by polymorphisms in ALAD and GPx gene. Further, the rs1800435 SNP showed a tendency to modulate ALAD activity, while the rs1800668 SNP did not modulate GPx activity in Brazilian automotive battery workers exposed to Pb.


Assuntos
Glutationa Peroxidase/genética , Chumbo/toxicidade , Metalurgia , Exposição Ocupacional , Sintase do Porfobilinogênio/genética , Adolescente , Adulto , Idoso , Automóveis , Brasil , Estudos Transversais , Glutationa Peroxidase/sangue , Humanos , Chumbo/sangue , Espectrometria de Massas , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Sintase do Porfobilinogênio/sangue , Reação em Cadeia da Polimerase em Tempo Real , Reciclagem , Adulto Jovem , Glutationa Peroxidase GPX1
5.
Res Vet Sci ; 93(3): 1309-13, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22387140

RESUMO

The aim of this study was to evaluate lipid peroxidation, protein oxidation and activity of enzymes that are indicators of oxidative stress in Rangelia vitalii infection in dogs. Animals were divided into two groups: negative control (n=5) and infected with R. vitalii (n=7). After inoculation, the parasitemia was estimated daily by microscopic examination of smears. Lipid peroxidation (TBARS) and advanced oxidation protein products (AOPP); and delta-aminolevulinate dehydratase (δ-ALA-D), superoxide dismutase (SOD) and catalase (CAT) activities in blood were evaluated. The samples were collected at days 10 and 20 post-inoculation (PI). TBARS and AOPP levels were higher in the infected group in both analyzed periods (P<0.01). The δ-ALA-D activity was reduced in blood of dogs infected with R. vitalii on days 10 and 20 PI. SOD activity was significantly increased (P<0.01) in the blood of dogs infected with R. vitalii at days 10 and 20 PI, while CAT activity was significantly increased (P<0.01) only at day 20 PI when compared to non-infected animals. A positive correlation was observed between the degree of parasitemia and TBARS and AOPP levels and activity of antioxidant enzymes. The δ-ALA-D activity was negatively correlated with the degree of parasitemia. Based on the increased levels of TBARS, AOPP, SOD and CAT activities, and inhibition δ-ALA-D activity, we concluded that dogs experimentally infected with R. vitalii develop a state of redox unbalance and that these changes might be involved in the pathophysiology of disease.


Assuntos
Apicomplexa/fisiologia , Doenças do Cão/parasitologia , Estresse Oxidativo/fisiologia , Infecções Protozoárias em Animais/parasitologia , Produtos da Oxidação Avançada de Proteínas/metabolismo , Animais , Apicomplexa/classificação , Catalase/genética , Catalase/metabolismo , Cães , Feminino , Regulação Enzimológica da Expressão Gênica , Parasitemia , Sintase do Porfobilinogênio/genética , Sintase do Porfobilinogênio/metabolismo , Infecções Protozoárias em Animais/patologia , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo
6.
Environ Health ; 10: 97, 2011 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-22074419

RESUMO

BACKGROUND: Given mounting evidence for adverse effects from excess manganese exposure, it is critical to understand host factors, such as genetics, that affect manganese metabolism. METHODS: Archived blood samples, collected from 332 Mexican women at delivery, were analyzed for manganese. We evaluated associations of manganese with functional variants in three candidate iron metabolism genes: HFE [hemochromatosis], TF [transferrin], and ALAD [δ-aminolevulinic acid dehydratase]. We used a knockout mouse model to parallel our significant results as a novel method of validating the observed associations between genotype and blood manganese in our epidemiologic data. RESULTS: Percentage of participants carrying at least one copy of HFE C282Y, HFE H63D, TF P570S, and ALAD K59N variant alleles was 2.4%, 17.7%, 20.1%, and 6.4%, respectively. Percentage carrying at least one copy of either C282Y or H63D allele in HFE gene was 19.6%. Geometric mean (geometric standard deviation) manganese concentrations were 17.0 (1.5) µg/l. Women with any HFE variant allele had 12% lower blood manganese concentrations than women with no variant alleles (ß = -0.12 [95% CI = -0.23 to -0.01]). TF and ALAD variants were not significant predictors of blood manganese. In animal models, Hfe(-/-) mice displayed a significant reduction in blood manganese compared with Hfe(+/+) mice, replicating the altered manganese metabolism found in our human research. CONCLUSIONS: Our study suggests that genetic variants in iron metabolism genes may contribute to variability in manganese exposure by affecting manganese absorption, distribution, or excretion. Genetic background may be critical to consider in studies that rely on environmental manganese measurements.


Assuntos
Antígenos de Histocompatibilidade Classe I/genética , Manganês/sangue , Proteínas de Membrana/genética , Sintase do Porfobilinogênio/genética , Transferrina/genética , Animais , Feminino , Genótipo , Proteína da Hemocromatose , Humanos , Ferro/sangue , Ferro/metabolismo , Manganês/metabolismo , Espectrometria de Massas , México , Camundongos , Camundongos Knockout , Modelos Animais , Reação em Cadeia da Polimerase Multiplex , Polimorfismo de Nucleotídeo Único/genética , Período Pós-Parto , Análise de Regressão , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Espectrofotometria Atômica , Adulto Jovem
7.
Toxicol Lett ; 191(2-3): 236-9, 2009 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-19766174

RESUMO

Delta-aminolevulinic acid dehydratase (ALAD) is a cytosolic enzyme in the heme biosynthetic pathway. The ALAD is controlled by two codominant alleles (ALAD1 and ALAD2), which result in a Asn-Lys substitution at amino acid position 59 of the mature enzyme based on a single nucleotide polymorphism (SNP) (G177C) leading three phenotypes (ALAD1-1, ALAD1-2, and ALAD2-2). Previous studies have shown that this polymorphism is related to lead toxicity. There is little evidence showing interethnic differences in the distribution of this polymorphism. We examined the distribution of genetic variants of the ALAD G177C polymorphism in four Asians, three Africans, and three Mexicans. Genomic DNA was extracted from blood or bloodstain, and the genotypes for the ALAD polymorphism were determined by PCR followed by RFLP digestion and gel electrophoresis. We found a notable interethnic disparity in the distribution of ALAD G177C genotypes and alleles. The frequencies of ALAD2 in Asian populations were comparable to those in Caucasians, while Africans had no mutation allele. These findings may help us understand the interethnic disparities in susceptibility to lead toxicity.


Assuntos
Sintase do Porfobilinogênio/genética , África/epidemiologia , Alelos , Ásia/epidemiologia , Povo Asiático , População Negra , Eletroforese em Gel de Poliacrilamida , Genótipo , Humanos , Indígenas Centro-Americanos , México/epidemiologia , Polimorfismo Genético , Polimorfismo de Fragmento de Restrição
8.
Basic Clin Pharmacol Toxicol ; 102(4): 347-51, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18282196

RESUMO

Pregnant women are one of the most sensitive populations to the toxic effects associated with lead (Pb) exposure. These effects are primarily associated with plasma Pb (Pb-P), which reflects the most rapidly exchangeable fraction of Pb in the bloodstream, and elevated maternal Pb-P may be more relevant to foetal Pb exposure than whole blood Pb (Pb-B). We investigated how pregnancy affects Pb-B, Pb-P and %Pb-P/Pb-B ratios without the influence of the delta-aminolevulinic acid dehydratase (ALAD) G177C polymorphism, which is a major genetic factor influencing Pb-B, Pb-P and %Pb-P/Pb-B ratios. Genotypes for the ALAD G177C polymorphism were determined by PCR and restriction fragment length digestion in nine pregnant and 20 non-pregnant women, aged 18-33, environmentally exposed to Pb. Here, we included only women with ALAD 1-1 genotype. Pb-P and Pb-B were determined by inductively coupled plasma mass spectrometry and by graphite furnace atomic absorption spectrometry, respectively. We found no differences in Pb-B (P > 0.05). However, pregnant women had a 2-fold increase in Pb-P and a 3-fold increase in %Pb-P/Pb-B (both P < 0.01) compared to non-pregnant women. These alterations in Pb concentrations associated with pregnancy are similar to those associated with different ALAD gene variants. We can now better appreciate how pregnancy affects foetal exposure to Pb without the influence of this important genetic factor.


Assuntos
Exposição Ambiental , Poluentes Ambientais/sangue , Chumbo/sangue , Polimorfismo de Fragmento de Restrição , Sintase do Porfobilinogênio/genética , Adulto , Poluentes Ambientais/toxicidade , Feminino , Feto/metabolismo , Genótipo , Humanos , Chumbo/toxicidade , Troca Materno-Fetal , Sintase do Porfobilinogênio/metabolismo , Gravidez , Medição de Risco
9.
Comp Biochem Physiol C Toxicol Pharmacol ; 147(2): 198-204, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17936691

RESUMO

The main objective of the present study was to compare the inhibitory effect of diphenyl diselenide (PhSe)(2) and Pb(2+) on mice and fruit fly delta-Aminolevulinate dehydratase (delta-ALA-D). Optimum pH was quite different for mice (pH 6.5) and flies (pH 8.5). At pH 8.5, the inhibitory potency of (PhSe)(2) was higher for the fruit flies (IC(50) 8.2 micromol/l) than for mice (IC(50) 19.5 micromol/l). Pb(2+) inhibited mice delta-ALA-D at pH 6.5 (IC(50) 6.2 micromol/l) and 8.5 (IC(50) 5.6 micromol/l) with higher potency than the fly enzyme (IC(50) 43.7 micromol/l). delta-ALA-D transcription was reduced by 15% in flies exposed to 0.3 mmol/kg (PhSe)(2), which is similar to the reduction observed in activity measured in the presence of dithiothreitol. The three-dimensional prediction by SWISS-PROT mouse and fly delta-ALA-D revealed differences in the number of hydrogen bonds and turns for the 2 enzymes. Sulfhydryl groups (-SH) that could be oxidized by (PhSe)(2) are conserved in the two sources of enzyme. Distinct responsiveness to pH, (PhSe)(2) and Pb(2+) of these enzymes may be related to subtle differences in tertiary or quaternary structure of mouse and fly delta-ALA-D. Furthermore, mechanism underlying enzyme inhibition after in vivo exposure seems to be different for Drosophila melanogaster and rodent enzymes.


Assuntos
Derivados de Benzeno/toxicidade , Drosophila melanogaster/enzimologia , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Compostos Organosselênicos/toxicidade , Sintase do Porfobilinogênio/genética , Transcrição Gênica/efeitos dos fármacos , Animais , Masculino , Camundongos , Sintase do Porfobilinogênio/antagonistas & inibidores
10.
Clin Chim Acta ; 367(1-2): 192-5, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16445899

RESUMO

BACKGROUND: delta-Aminolevulinic acid dehydratase (ALAD) catalyzes the second step of heme synthesis. The ALAD gene shows a polymorphism (G-to-C transversion at position 177) leading to 2 alleles (ALAD1 and ALAD2) and 3 phenotypes (ALAD 1-1, ALAD 1-2 and ALAD 2-2). This polymorphism has been shown to affect lead toxicity and the risk of meningioma. In addition, there is little evidence showing interethnic differences in the distribution this polymorphism, especially in heterogeneous populations such as the present-day Brazilian population. We examined the distribution of genetic variants of the G177C ALAD polymorphism in black and white Brazilians. METHODS: We studied 115 subjects self-reported as black and 119 subjects as white (total N=234; 135 men and 99 women; age range: 18-60 years). Genomic DNA was extracted from venous blood and the genotypes for the ALAD polymorphism were determined by PCR followed by RFLP digestion and gel electrophoresis. RESULTS: We found a notable interethnic disparity in the distribution of G177C ALAD genotypes and alleles. The ALAD2 allele was more common in whites (12%) than in blacks (4%) (P<0.05). Correspondingly, the heterozygote (ALAD 1-2) or homozygote variant (ALAD 2-2) genotypes for this polymorphism were more common in whites than in blacks (P<0.05). CONCLUSIONS: The significant interethnic differences in the distribution of G177C ALAD variants found in the Brazilian population is consistent with differences previously reported in other countries. These findings may help us understand the interethnic disparities in susceptibility to lead toxicity and brain tumors.


Assuntos
Variação Genética/genética , Sintase do Porfobilinogênio/genética , Adolescente , Adulto , Alelos , Brasil/etnologia , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade
11.
Arch Toxicol ; 80(7): 394-8, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16341691

RESUMO

Delta aminolevulinic acid dehydratase (ALAD) plays an important role in lead poisoning. This study was carried out to examine the effects of ALAD gene polymorphism (G177C) on %Pb-P(plasma lead)/Pb-B(whole blood) ratio in 142 subjects environmentally exposed to lead. Genotypes for the ALAD G177C polymorphism were determined by PCR and restriction fragment length digestion. Pb-P and Pb-B were determined by inductively coupled plasma mass spectrometry and by graphite furnace atomic absorption spectrometry, respectively. The allele frequencies for ALAD1 and ALAD2 alleles were 0.897 and 0.103, respectively. We combined both ALAD 1-2 and ALAD 2-2 genotypes together (ALAD 1-2/2-2 group) and compared with the ALAD 1-1 genotype group. While no significant differences were found in Pb-B, subjects from the ALAD 1-2/2-2 genotype group presented significantly higher Pb-P concentrations and %Pb-P/Pb-B ratios (0.89+/-0.07 microg/l, and 1.45+/-0.10%, respectively) when compared with subjects from the ALAD 1-1 genotype group (0.44+/-0.05 microg/l, and 0.48+/-0.02, respectively; both P<0.0001). The higher %Pb-P/Pb-B ratios in carriers of the ALAD-2 allele compared with noncarriers indicate that ALAD 1-2/2-2 subjects are probably at increased health risks associated with lead exposure.


Assuntos
Exposição Ambiental/análise , Intoxicação por Chumbo/genética , Chumbo/sangue , Polimorfismo de Fragmento de Restrição , Sintase do Porfobilinogênio/genética , Adolescente , Adulto , Brasil , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Intoxicação por Chumbo/metabolismo , Masculino , Pessoa de Meia-Idade , Sintase do Porfobilinogênio/sangue
12.
Arch Environ Contam Toxicol ; 47(2): 276-80, 2004 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15386154

RESUMO

Childhood environmental lead exposure in the city of Antofagasta, Chile, was generated by the accumulation of recently removed lead stores derived from mining activities for a long period of time. Susceptibility to harmful lead effects may be associated with polymorphisms of delta-aminolevulinic acid dehydratase (ALAD) because of the differential binding of lead to the codified proteins. We assessed the associations and possible interactions among the following variables: blood lead levels, ALAD genotypes, and distance to the source of lead contamination in Chilean children exposed to lead contamination in Antofagasta, Chile. Ninety-three children were recruited from schools located near a lead- contaminated area. Lead blood levels were measured by atomic absorption spectrophotometry. ALAD genotypes were determined by polymerase chain reaction and restriction fragment-length polymorphism analysis. The frequency of the ALAD-2 allele was estimated at 0.054. Children with the ALAD-2 genotype had higher blood lead levels than noncarriers (p = 0.06). As expected, blood lead levels were inversely correlated with the distance from lead stores. Interestingly, ALAD-2 carriers were more frequent within the area defined by a distance of 200 m from lead deposits (27%) than in areas >200 m (5%) away. Children living within a maximum distance of 200 m from the lead stores showed higher blood lead levels in ALAD-2 carriers (geometric mean = 16.4 microg/dl, range 6 to 27) than in noncarriers (geometric mean = 12.1 microg/dl, range 0 to 26) without achieving statistical significance (p = 0.13). A trend for higher blood lead levels in ALAD-2 carriers compared with ALAD-1 homozygous children has been observed. Because ALAD-2 frequency was higher in subjects living within 200 m from the lead deposits, we hypothesized that a long-term selective pressure against the presence of the ALAD-1 allele is the cause of the overrepresentation of the ALAD-2 allele in children living in proximity to the recently removed lead stores.


Assuntos
Proteção da Criança , Exposição Ambiental , Poluentes Ambientais/sangue , Intoxicação por Chumbo/etiologia , Chumbo/sangue , Sintase do Porfobilinogênio/genética , Criança , Pré-Escolar , Chile , Feminino , Genótipo , Humanos , Masculino , Mineração , Instituições Acadêmicas
13.
Gene Geogr ; 5(1-2): 33-7, 1991.
Artigo em Inglês | MEDLINE | ID: mdl-1820152

RESUMO

Electrophoretic polymorphism of delta-aminolevulinate dehydrase (ALAD) was studied on 519 individuals from Bahia, Brazil. Subjective assessment of Black ancestries carried out in a five point visual scale (White, Light Mulatto, Medium Mulatto, Dark Mulatto and Black) allowed to show that the ALAD*2 allele frequency decreases from 8% in Whites to 0% in Blacks. These findings agree with previous reports of ALAD in Africans, American Indians and Spanish. The powerful peculiarity of the ALAD system in assessing racial admixture is stressed.


Assuntos
População Negra/genética , Polimorfismo Genético/genética , Sintase do Porfobilinogênio/genética , População Branca/genética , Alelos , Brasil , Feminino , Humanos , Fenótipo
14.
Yeast ; 6(4): 319-30, 1990.
Artigo em Inglês | MEDLINE | ID: mdl-2204246

RESUMO

Saccharomyces cerevisiae transformed with a multicopy plasmid carrying the yeast structural gene HEM2, which codes for delta-aminolevulinate dehydratase, was enriched 20-fold in the enzyme. Beginning with cell-free extracts of transformed cells, the dehydratase was purified 193-fold to near-homogeneity. This represents a 3900-fold purification relative to the enzyme activity in normal, untransformed yeast cells. The specific activity of the purified enzyme was 16.2 mumol h-1 per mg protein at pH 9.4 and 37.5 degrees C. In most respects the yeast enzyme resembles mammalian enzymes. It is a homo-octamer with an apparent Mr of 275,000, as determined by centrifugation in glycerol density gradients, and under denaturing conditions behaved as a single subunit of Mr congruent to 37,000. The enzyme requires reduced thiol compounds to maintain full activity, and maximum activity was obtained in the presence of 1.0 mM-Zn2+. It is sensitive to inhibition by the heavy metal ions Pb2+ and Cu2+. The enzyme exhibits Michaelis-Menten kinetics and has an apparent Km of 0.359 mM. Like dehydratases from animal tissues, the yeast enzyme is rather thermostable. During the purification process an enhancement in total delta-aminolevulinate dehydratase activity suggested the possibility that removal of an inhibitor of the enzyme could be occurring.


Assuntos
Sintase do Porfobilinogênio/isolamento & purificação , Saccharomyces cerevisiae/enzimologia , Concentração de Íons de Hidrogênio , Cinética , Plasmídeos , Porfobilinogênio/metabolismo , Sintase do Porfobilinogênio/genética , Sintase do Porfobilinogênio/metabolismo , Protaminas , Saccharomyces cerevisiae/genética , Compostos de Sulfidrila , Temperatura , Transformação Genética , Zinco/farmacologia
15.
Hum Genet ; 67(3): 343-6, 1984.
Artigo em Inglês | MEDLINE | ID: mdl-6088389

RESUMO

Aldehyde dehydrogenase deficiency, N-acetyltransferase variation and the polymorphisms of alpha 1-antitrypsin, serum cholinesterase, paraoxonase, and delta-aminolevulinic acid dehydratase were investigated in 180 Atacameño Indians from the North of Chile. The genetic predisposition of these individuals for possible atypical reactions against environmental agents and drugs, as well as general implications of these findings, are discussed.


Assuntos
Indígenas Sul-Americanos , Isoenzimas/genética , Aldeído Oxirredutases/deficiência , Aldeído Oxirredutases/genética , Arildialquilfosfatase , Chile , Colinesterases/sangue , Colinesterases/genética , Frequência do Gene , Humanos , Isoenzimas/deficiência , Monoéster Fosfórico Hidrolases/genética , Sintase do Porfobilinogênio/genética , alfa 1-Antitripsina/genética
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