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1.
Chinese Journal of Biotechnology ; (12): 1494-1503, 2013.
Article in Chinese | WPRIM | ID: wpr-242462

ABSTRACT

5-aminolevulinic acid (ALA), a precursor for biosynthesis of pyrrole compounds in living organisms, has been widely used in agriculture and medical photodynamics therapy and is regarded as a promising value-added bio-based chemical. In the previous investigations on ALA production with recombinant Escherichia coli expressing heterogenous C4 pathway gene, LB media supplemented with glucose and ALA precursors succinate and glycine is widely used, leading to high production cost. Succinate participates in ALA biosynthesis in a form of succinyl-CoA. In this study, genes involved in succinyl-CoA consumption, sdhAB (encoding succinic dehydrogenase) or sucCD (encoding succinyl-CoA synthetase) of E. coli MG1655 was knocked out and tested for ALA accumulation. In comparison with the recombinant E. coli strain expressing heterogenous ALA synthetase, the sdhAB- or sucCD-deficient strain accumulate 25.59% and 12.40%, respectively, more ALA in a 5 L fermentor using a defined synthetic medium with glucose as main carbon source and without supplementation of succinate, providing a novel cost-effective approach for industrial production of ALA.


Subject(s)
Aminolevulinic Acid , Metabolism , Escherichia coli , Genetics , Metabolism , Industrial Microbiology , Methods , Metabolic Engineering , Methods , Recombinant Proteins , Genetics , Metabolism , Succinate Dehydrogenase , Genetics , Metabolism , Succinate-CoA Ligases , Genetics , Metabolism
2.
Rev. colomb. cir ; 26(2): 131-137, abr.-jun. 2011. tab
Article in Spanish | LILACS | ID: lil-593541

ABSTRACT

La porfiria intermitente aguda es conocida, en el ámbito de la cirugía, como una de las causas de abdomen agudo no quirúrgico. No obstante, lo que no se menciona con frecuencia es la posibilidad de que cualquier procedimiento quirúrgico precipite un episodio agudo en pacientes con predisposición genética. Se presenta un caso florido de porfiria intermitente aguda precipitado por una apendicectomía, el cual complicó el posoperatorio de la paciente hasta el punto de requerir una laparotomía no terapéutica, dado el complejo sintomático de difícil interpretación.


Acute porphyria is an uncommon cause of non surgical acute abdomen. Important is the fact that any surgical intervention could set off an acute attack in particular cases, when the patient has genetical predisposition. We present a case of an acute attack of Intermitent Acute Porphyria triggered by an appendectomy. The patient developed the typical syndrome during the postoperative period, including the abdominal symptoms that imitate an acute abdomen that required a non- therapeutic laparotomy.


Subject(s)
Humans , Abdomen, Acute , Abdominal Pain , Aminolevulinic Acid , Porphobilinogen , Porphyria, Acute Intermittent , Porphyrias
3.
Korean Journal of Pediatric Gastroenterology and Nutrition ; : 81-85, 2011.
Article in Korean | WPRIM | ID: wpr-190242

ABSTRACT

Acute intermittent porphyria (AIP) is a rare disorder characterized biochemically by the increased excretion of porphyrins and porphyrin precursors, including delta-aminolevulinic acid (ALA) and porphobilinogen (PBG). AIP has variable clinical manifestations, such as acute abdominal pain, vomiting, nausea, constipation, peripheral neuropathy, seizures, tachycardia, and hypertension. A 16-year-old girl presented with recurrent abdominal pain, vomiting, hypertension, seizures, hypercholesterolemia, and red urine. AIP was confirmed by clinical features and increased 24-hour urine ALA and PBG. AIP should be considered in the differential diagnosis of patients who have abdominal pain, hypertension, and seizures when the results of all other tests are normal.


Subject(s)
Adolescent , Humans , Abdominal Pain , Aminolevulinic Acid , Constipation , Diagnosis, Differential , Hypercholesterolemia , Hypertension , Nausea , Peripheral Nervous System Diseases , Porphobilinogen , Porphyria, Acute Intermittent , Porphyrins , Seizures , Tachycardia , Vomiting
4.
An. bras. dermatol ; 85(4): 501-511, jul.-ago. 2010. ilus
Article in Portuguese | LILACS | ID: lil-560580

ABSTRACT

A terapia fotodinâmica é uma reação química ativada por luz usada para destruição seletiva de um tecido e requer um agente fotossensibilizante no tecido-alvo, uma fonte de luz e oxigênio. Estão disponíveis, no momento, o ácido 5-aminolevulínico para tratamento de ceratoses actínicas e o metilaminolevulinato, aprovado para tratamento de ceratoses actínicas, carcinoma basocelular e doença de Bowen. As fontes de luz utilizadas para a terapia fotodinâmica devem emitir comprimentos de onda no espectro de absorção do fotossensibilizante escolhido. As lâmpadas LED (light emitting diode) são as indicadas para terapia fotodinâmica tópica no tratamento do câncer de pele não melanoma. A terapia fotodinâmica deve ser considerada, em particular, para pacientes que apresentam lesões superficiais, múltiplas, disseminadas e para pacientes imunossuprimidos. Mais recentemente, a terapia fotodinâmica tem sido indicada no tratamento do fotoenvelhecimento, acne, hidrosadenite, esclerodermia, psoríase, verrugas, leishmaniose, entre outras. Por este trabalho será possível ter acesso a uma extensa revisão da literatura sobre terapia fotodinâmica, seus mecanismos, indicações e resultados, seguida de comentários e críticas pertinentes ao assunto.


Photodynamic therapy (PDT) consists of a chemical reaction activated by light energy that is used to selectively destroy tissue. The reaction requires a photosensitizer in the target tissue, a light source and oxygen. The most extensively studied photosensitizing agents for PDT are 5-aminolevulinic acid for the treatment of actinic keratosis and methyl-aminolevulinate, which has been approved for the treatment of actinic keratosis, basal cell carcinoma and Bowen's disease. The light sources used in photodynamic therapy should emit light at wavelengths within the absorption spectrum of the photosensitizer used in PDT treatment. Light emitting diode (LED) lamps are indicated for the photodynamic treatment of nonmelanoma skin cancer. PDT should be considered as a therapeutic option, particularly in the case of patients with superficial, multiple or disseminated lesions and for immunosuppressed patients. More recently, PDT has been indicated for a wide range of dermatological conditions such as photo-damaged skin, acne, hidradenitis, scleroderma, psoriasis, warts and leishmaniosis, among others. This article provides an extensive review of photodynamic therapy, its mechanisms, indications and results.


Subject(s)
Humans , Aminolevulinic Acid/analogs & derivatives , Photochemotherapy/methods , Photosensitizing Agents/therapeutic use , Skin Diseases/drug therapy , Aminolevulinic Acid/therapeutic use
5.
São Paulo; s.n; 2009. 219 p. ilus, tab, graf.
Thesis in Portuguese | LILACS | ID: lil-593589

ABSTRACT

Para otimizar urn modelo experimental para o estudo do desbalanço redox em porfirias relacionadas ao acúmulo de ácido 5-aminolevulinico-(ALA), via inibição da ALA desidratase-(ALA-D), ratos foram tratados com o éster metílico de succinilacetona-(SAME), um catabólito da tirosina que inibe fortemente a ALA-D, mimetizando o estado metabólico observado nos portadores de porfirias e tirosinemias. Estabeleceram-se modelos de tratamento agudo por 36 e 18 h. No primeiro, os animais receberam 3 injeções de SAME (10, 40 ou 80 mg/kg, grupos All-IV). No segundo, os animais receberam 3 injeções de 40 mg/kg de SAME, ALA ou éster metílico de ALA (grupos BII-IV), ALA:SAME (30:10 mg/kg, grupo BV), ou 10 mg/kg SAME (grupo BVI). Paralelamente, avaliou-se se os sintomas neurológicos característicos das porfirias decorriam de danos oxidativos mitocondriais. Para isso, aplicou-se uma tecnologia óptica para medidas da difusão da depressão cortical que determinou a oxigenação e o estado redox do cit c em mitocôndrias do córtex cerebral de ratos submetidos ao tratamento crônico com ALA (40 mg/kg), SAME (10 e 40 mg/kg) e ALA:SAME (30:10 mg/kg), a cada 48 h, durante 30 dias. Tratamento agudo/36 h: Os níveis de ALA no plasma, fígado, cérebro e urina e o clearance renal do ALA aumentaram nos grupos tratados. A atividade de ALA-D e a coproporfirina urinaria reduziram. A marcação para proteínas carboniladas, ferro e ferritina aumentou no fígado e cérebro dos grupos tratados, especialmente no All. Os níveis de malondialdeído hepática aumentaram no grupo AIV. A razão GSH/GSH+GSSG e a atividade de GPx cerebrais aumentaram nos grupos AIV e AIII, respectivamente. Consistentemente com estes dados indicando um desbalanço oxidativo induzido pelo SAME, alterações mitocondriais e citosólicas ultraestruturais foram reveladas, especialmente no fígado./Tratamento agudo/18 h: Os níveis de ALA plasmáticos aumentaram nos grupos tratados, exceto em BIV. 0 grupo Bll mostrou aumento dos níveis hepáticos...


To optimize an experimental model for studying redox imbalance in porphyrias related to 5-aminolevulinic acid (ALA) accumulation through the inhibition of ALA dehydratase (ALA-D), rats were treated with methyl ester of succinylacetone (SAME), a tyrosine catabolite that strongly inhibits ALA-D, what mimics the metabolic state observed in patients suffering from porphyrias and tyrosinemias. Models of acute treatment were established during 36 and 18 h. In the first model, animals received 3 injections of SAME (10, 40 or 80 mg/kg, groups All-IV). In the second model, animals received 3 injections of 40 mg/kg SAME, ALA or methyl ester of ALA (groups BII-IV), ALA:SAME (30:10 mg/kg, group BV), or 10 mg/kg SAME (group BVI). Concomitantly, we evaluated if the neurologic symptoms characteristics of porphyrias were a consequence of the oxidative mitochondria! impairment. For this, an optical technology for the measurement of cortical spreading depression was applied. This techonology determined the cerebral oxygenation and the redox state of cit c in mitochondria of the cerebral cortex of rats submitted to a chronic treatment with ALA (40 mg/kg), SAME (10 and 40 mg/kg) and ALA:SAME (30:10 mg/kg), alternate days, during 30 days. Acute treatment/36 h: ALA levels in plasma, liver and urine and clearance of renal ALA increased in treated groups. ALA-D activities and urinary coproporphyrin were found to be decreased. Liver and brain proteins carbonyl, iron and ferritin were higher in the liver of treated groups, especially in All. Liver j malondialdehyde levels were higher in group AIV. Cerebral GSH/GSH+GSSG ratio and GPx activities increased in groups AIV and AIII, respectively. Consistently with these data indicating SAME-induced oxidative imbalance, mitochondrial and cytosolic ultrastructural changes were revealed, especially in the liver. Acute treatment/18 h: Plasma ALA levels increased in all treated groups but BIV. Group BII showed increased hepatic ALA levels…


Subject(s)
Animals , Male , Young Adult , Rats , Aminolevulinic Acid/antagonists & inhibitors , Disease Models, Animal , Intervention Studies , Hydro-Lyases , Oxidative Stress , Porphyrias, Hepatic/chemically induced , Mitochondria , Porphyria, Acute Intermittent , Tyrosinemias
6.
Indian J Exp Biol ; 2007 Apr; 45(4): 385-9
Article in English | IMSEAR | ID: sea-57534

ABSTRACT

Supply of cadmium chloride (0.5 mM) inhibited chlorophyll formation in greening maize leaf segments, while lower concentration of Cd (0.01 mM) slightly enhanced it. Inclusion of 2-oxoglutarate (2-OG, 0.1-10 mM) in the incubation mixture increased chlorophyll content in the absence as well as presence of Cd. Substantial inhibition of chlorophyll formation by Cd was observed at longer treatment both in the absence and presence of 2-OG. When the tissue was pre-incubated with 2-OG or Cd, the inhibition (%) of chlorophyll formation by Cd was lowered in the presence of 2-OG. Treatment with Cd inhibited ALAD activity and ALA formation and the inhibition (%) of ALA formation by Cd was strongly reduced in the presence of 2-OG. Glutamate dehydrogenase (GDH) activity was increased by the supply of Cd both in the absence as well as presence of 2-OG. In the presence of 2-OG, Cd supply significantly increased glutamate synthase (GOGAT) activity and reduced inhibition (%) of glutamine synthetase (GS) activity. The results suggested the involvement of the glutamine synthetase/glutamate synthase (GS/GOGAT) pathway of ammonia assimilation to provide the precursor, glutamate, for ALA synthesis under Cd toxicity and 2-OG supplementation.


Subject(s)
Aminolevulinic Acid/antagonists & inhibitors , Cadmium Chloride/pharmacology , Chlorophyll/antagonists & inhibitors , Ketoglutaric Acids/pharmacology , Plant Leaves/drug effects , Porphobilinogen Synthase/antagonists & inhibitors , Quaternary Ammonium Compounds/metabolism , Zea mays/drug effects
7.
Chinese Journal of Biotechnology ; (12): 520-524, 2007.
Article in Chinese | WPRIM | ID: wpr-327993

ABSTRACT

Aminolevulinic acid (ALA) is biosynthesized by the enzyme ALA synthase (ALAS). The ALA production has been studied using the overproducing ALAS from several bacteria in Escherchia coil, respectively. However, ALAS from eucaryote expressed in E. coli for producing ALA in the culture is not known. The extracellular ALA production and cell growth were investageted respectively using the recombinant E. coli overproducing Saccharomyces cerevisiae ALAS in shake-flask fermentations. The ALAS activity from the cell extract was assayed. The extracellular ALA was purified by the national-made large-dimension resins and confirmed by the capillary electrophoresis measurements. At 12h after induction at 37 degrees C, the extracellular ALA production was up to 162mg per liter LB culture at initial pH 6.5 with exogenous levulinate, succinate and and glycine at the concentration of 20 mmol/L respectively. The purity of ALA after purification is up to 90%.


Subject(s)
5-Aminolevulinate Synthetase , Genetics , Metabolism , Aminolevulinic Acid , Metabolism , Cell Division , Dose-Response Relationship, Drug , Electrophoresis, Capillary , Escherichia coli , Genetics , Metabolism , Extracellular Space , Metabolism , Glycine , Pharmacology , Hydrogen-Ion Concentration , Levulinic Acids , Pharmacology , Recombinant Proteins , Metabolism , Saccharomyces cerevisiae , Genetics , Saccharomyces cerevisiae Proteins , Genetics , Metabolism , Succinic Acid , Pharmacology
8.
Indian J Exp Biol ; 2004 Apr; 42(4): 419-23
Article in English | IMSEAR | ID: sea-56760

ABSTRACT

Mercury (0.01-1.0 mM) inhibited chlorophyll formation in greening maize leaf segments. However, supplementing incubation medium with 2-oxoglutarate, maintained substantially higher level of chlorophyll in absence of metal after an initial period of 8 hr. On preincubation of leaf segments with HgCl2, per cent inhibition of chlorophyll synthesis by metal was same in the presence and absence of 2-oxoglutarate. Supply of 2-oxoglutarate (0.1-10.0 mM) exerted concentration dependent effect on chlorophyll formation in absence or presence of metal. Increase in delta-amino levulinic acid dehydratase as well as NADH-glutamate synthase activity and decrease in NADH-glutamate dehydrogenase activity by 2-oxoglutarate in the presence of Hg suggested that glutamate for delta-amino levulinic acid synthesis could be made available from NH4+ assimilation via., glutamine synthetase/glutamate synthase pathway during mercury toxicity.


Subject(s)
Aminolevulinic Acid/metabolism , Ammonia/metabolism , Chlorophyll/biosynthesis , Dose-Response Relationship, Drug , Glutamate Synthase/metabolism , Glutamic Acid/metabolism , Ketoglutaric Acids/pharmacology , Light , Mercury/toxicity , NAD/metabolism , Photosynthesis , Plant Leaves/drug effects , Porphobilinogen Synthase/metabolism , Radiation-Protective Agents/pharmacology , Zea mays/drug effects
9.
RBCF, Rev. bras. ciênc. farm. (Impr.) ; 38(3): 249-257, jul.-set. 2002. ilus, tab
Article in Portuguese | LILACS | ID: lil-334616

ABSTRACT

As porfirias são causadas por deficiência parcial de uma das enzimas da via de biossíntese do heme, caracterizando-se por disfunções neuroviscerais bastante semelhantes. As profirias agudas são decorrentes da deficiência das enzimas delta-aminolevulinato desidratase (ALAD), porfobilinogênio desaminase, coproporfirinogênio oxidase ou protoporfirinogênio oxidase, que provocam, respectivamente, porfiria por deficiência da ALAD, porfiria aguda intermitente, coproporfiria hereditária e porfiria variegada. Todas as porfirias agudas caracterizam-se por um aaumento na concentração de ácido 5-aminolevulínico no plasma e no líquor, acompanhado de um aumento na excreção urinária deste composto...


Subject(s)
Humans , Adult , Aminolevulinic Acid/analysis , DNA , Mutation/genetics , Porphobilinogen/analysis , Porphyria, Acute Intermittent , Porphyrins , Blood , Feces , Specimen Handling , Urine
11.
São Paulo; s.n; 2000. 203 p. ilus, tab, graf.
Thesis in Portuguese | LILACS | ID: lil-276131

ABSTRACT

O ácido 5-aminolevulínico (ALA) é o primeiro precursor do grupo heme acumulado, principalmente no fígado, em alguns tipos de porfirias hepáticas hereditárias (porfiria aguda intermitente-AIP e tirosinemia) ou adquiridas (intoxicação por chumbo) devido à diminuição da atividade da enzima porfobilinogênio deaminase. Amostras de biópsias de fígado de pacientes portadores de AIP revelaram alterações estruturais nas mitocôndrias e no retículo endoplasmático, acúmulo de lipofuscina, gordura e corpúsculos de ferritina. Têm sido demonstrado que mutações mitocondriais induzidas por pró-oxidantes também contribuem para o envelhecimento celular e para o desenvolvimento do câncer. Esses dados podem estar relacionados à maior incidência de carcinoma hepatocelular (HCC) em pacientes sintomáticos de AIP...


Subject(s)
Animals , Rats , Aminolevulinic Acid/toxicity , Carcinoma, Hepatocellular , DNA Damage , Free Radicals , Porphyria, Acute Intermittent , Chromatography, Gas , Chromatography, High Pressure Liquid/methods , Culture Media , Hydrolysis , Mass Spectrometry
12.
Säo Paulo; s.n; 1998. 144 p. ilus, tab, graf.
Thesis in Portuguese | LILACS | ID: lil-226203

ABSTRACT

Em alguns tipos de porfirias como porfiria aguda intermitente (PAI) e tirosinemia hereditária tipo (HT1) observa-se acúmulo do ácido 5-aminolevulínico (ALA) no sangue e tecidos. In vitro, o ALA sobre oxidaçäo pelo oxigênio molecular, catalisada por complexos de ferro, gerando o ácido 4,5-dioxovalérico (DOVA), íons NH4+, H2O2 e os radicais ALA, O2, e HO. ALA é capaz também de causar lesöes oxidativas a várias biomoléculas e inclusive induzir a liberaçäo de ferro de ferritina. Sendo assim, o ALA poderia agir como um pró-oxidante endógeno. Nossos estudos foram realizados com o objetivo de: 1) verificar a possibilidade de ocorrer processo autocatalítico durante a oxidaçäo do ALA em presença de ferritina de baço de cavalo (HoSF) e observar a influência de fosfato neste processo...


Subject(s)
Aminolevulinic Acid , Ferritins/biosynthesis , Liver/metabolism , Free Radicals , Kinetics , Porphyria, Acute Intermittent/metabolism , Catalysis , Electrochemistry , Electron Spin Resonance Spectroscopy , Iron Chelating Agents , Iron/metabolism , Oxidative Stress
13.
Braz. j. med. biol. res ; 29(7): 841-51, July 1996. ilus
Article in English | LILACS | ID: lil-181496

ABSTRACT

Highly reactive oxyradicals can be generated in vitro by iron-catalyzed aerobic oxidation of synthetic and naturally occuring substances capable of enolization in aqueous medium. Of biological interest are alfa-hydroxy- and alfa-aminocarbonyls such as carbohydrates, 5-aminolevulinic acid, and aminoacetone which tautomerize to the corresponding enediols and enolamines and yield oxyradicals initiated by electron transfer to dioxygen. Free radicals have been implicated in several normal and pathological processes. We briefly review our hypothesis of an in vivo prooxidant role of 5-aminolev-ulinic acid (ALA), the heme precursor accumulated in several porphyric disorders (e.g., lead poisoning, acute intermittent porphyria (AIP), tyrosinosis). Accordingly, i) ALA undergoes transition metal-catalyzed oxidation to give O-2, H2O2 and HO; ii) ALA induces iron release from ferritin, lipid peroxidation of cardiolipin-rich vesicles, single strand breaks in plasmid DNA, and guanosine oxidation in calf thymus DNA; iii) ALA causes Ca2+ -mediated rat liver mitochondria permeabilization; iv) rats chronically treated with ALA exhibit increased glycolytic metabolism; v) brain extracts of ALA-treated rats reveal increased levels of thiobarbituric acid reactive substances, direct chemiluminescence intensity, carbonyl proteins, ferritin, and "free iron"and gama-aminobutyric acid-receptor dissociation constant, and vi) patients with AIP and lead-exposed workers present augmented erythrocytic levels of the antioxidant enzymes superoxide dismutase and glutathione peroxidase. These data indicate the involvement of ALA-generated reactive species in the clinical manifestations (neuropathy, mental changes, muscle weakness, hepatoma) shared by the aforementioned inherited and acquired porphyric diseases.


Subject(s)
Humans , Animals , Rats , Aminolevulinic Acid/metabolism , Reactive Oxygen Species/metabolism , Lead Poisoning/metabolism , Oxidative Stress , Porphyria, Acute Intermittent/metabolism , Aminolevulinic Acid/pharmacology , Aminolevulinic Acid/urine , Calcium/metabolism , Cerebrum/drug effects , Cerebrum/metabolism , Heart , DNA Damage , Reactive Oxygen Species/pharmacology , Liver , Liver/metabolism , Heme/biosynthesis , Iron/metabolism , Mitochondria/metabolism , Lipid Peroxidation , Porphyrias/metabolism , Porphyrias/urine , Proteins/metabolism
14.
Egyptian Journal of Occupational Medicine. 1987; 11 (2): 131-138
in English | IMEMR | ID: emr-8642

ABSTRACT

Inhibition of Hb biosynthesis in lead intoxicated subjects appears as a result of disorder in the interaction of Cu, Zn and Fe ions on delta-Am-inolevulinic acid dehydratase. [ALA-D]. Elevation of free serum copper and decrease of serum iron and zinc are the main cause of ALAD inhibition. Thus, it is safe to suggest that administration of Zn orally leads to replacement of cu from catalytic sites of this enzyme which is known as a zinc dependent enzyme


Subject(s)
Humans , Male , Zinc/blood , Copper/blood , Iron/blood , 5-Aminolevulinate Synthetase , Aminolevulinic Acid/urine , Porphobilinogen Synthase , Lead/blood , Transferrin , Ceruloplasmin , Spectrophotometry, Atomic
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