RESUMO
LCHAD deficiency is a disorder of fatty acid beta oxidation. The most common clinical presentation includes disorders of consciousness, hypoglycemia and liver dysfunction triggered by prolonged fasting or infection. Once a metabolic crisis is triggered, there is a high mortality. HELLP syndrome and acute fatty liver failure of pregnancy (AFLP) are disorders of the third trimester of pregnancy. These diseases have been associated during pregnancy with hereditary defects of beta-oxidation in the fetus. We report a case of beta-oxidation disorder (LCHAD deficiency) associated with maternal HELLP. We described a peak of lipid and lactic on magnetic resonance spectroscopic of this patient. The investigation of these beta-oxidation disorders at birth, with a history of maternal HELLP, allows the diagnosis of the disease prior to developing symptoms.
Assuntos
3-Hidroxiacil-CoA Desidrogenases/deficiência , Síndrome HELLP , Erros Inatos do Metabolismo/diagnóstico , 3-Hidroxiacil-CoA Desidrogenases/genética , 3-Hidroxiacil-CoA Desidrogenases/metabolismo , Feminino , Humanos , Lactente , 3-Hidroxiacil-CoA Desidrogenase de Cadeia Longa , Espectroscopia de Ressonância Magnética , Masculino , Erros Inatos do Metabolismo/genética , Erros Inatos do Metabolismo/metabolismo , GravidezRESUMO
La deficiencia de 3-hidroxiacil coA deshidrogenasa de cadena larga (LCHAD) es uno de los trastornos de la betaoxidación de ácidos grasos. La presentación clínica más frecuente incluye trastornos de conciencia, hipoglucemia y disfunción hepática gatillados por ayuno prolongado o infecciones. Una vez desencadenada, la crisis metabólica presenta alta mortalidad. El síndrome HELLP y la hepatitis grasa aguda del embarazo (AFLP) son trastornos del tercer trimestre del embarazo. Se ha asociado estas enfermedades durante la gestación con defectos hereditarios de la betaoxidación en el feto. Comunicamos el caso clínico de un trastorno de beta oxidación (deficiencia de LCHAD) asociado a HELLP materno. Describimos como hallazgos en la resonancia magnética espectroscópica un pico de ácido láctico y lípidos significativo. La pesquisa de estos trastornos de la betaoxidación al nacimiento, ante el antecedente de HELLP materno, permite el diagnóstico de la enfermedad previo al desarrollo de los síntomas.(AU)
LCHAD deficiency is a disorder of fatty acid beta oxidation. The most common clinical presentation includes disorders of consciousness, hypoglycemia and liver dysfunction triggered by prolonged fasting or infection. Once a metabolic crisis is triggered, there is a high mortality. HELLP syndrome and acute fatty liver failure of pregnancy (AFLP) are disorders of the third trimester of pregnancy. These diseases have been associated during pregnancy with hereditary defects of beta-oxidation in the fetus. We report a case of beta-oxidation disorder (LCHAD deficiency) associated with maternal HELLP. We described a peak of lipid and lactic on magnetic resonance spectroscopic of this patient. The investigation of these beta-oxidation disorders at birth, with a history of maternal HELLP, allows the diagnosis of the disease prior to developing symptoms.(AU)
Assuntos
Feminino , Humanos , Lactente , Masculino , Gravidez , 3-Hidroxiacil-CoA Desidrogenases/deficiência , Síndrome HELLP , Erros Inatos do Metabolismo/diagnóstico , 3-Hidroxiacil-CoA Desidrogenases/genética , 3-Hidroxiacil-CoA Desidrogenases/metabolismo , Espectroscopia de Ressonância Magnética , Erros Inatos do Metabolismo/genética , Erros Inatos do Metabolismo/metabolismoRESUMO
Hypoxia can affect energy metabolism. We examined gene expression and enzyme activity related to mitochondrial energy metabolism, as well as myosin heavy chain (MyHC) types in yaks (Bos grunniens) living at high altitudes. Real-time quantitative PCR assays indicated that the yak has significantly lower levels of carnitine palmitoyltransferase (CPT) mRNA in the biceps femoris and lower levels of uncoupling protein 3 (UCP3) mRNA in both biceps femoris and longissimus dorsi than in Yellow cattle. No significant differences between yak and Yellow cattle were observed in the activities of mitochondrial ß-hydroxyacyl-CoA dehydrogenase, isocitrate dehydrogenase and cytochrome oxidase in the same muscles. Semi-quantitative RT-PCR analysis showed that the MyHC 1 mRNA levels in yak biceps femoris was lower than in Yellow cattle. We conclude that the yak has significantly lower mRNA levels of CPT, UCP3, and MyHC 1 in biceps femoris than in Yellow cattle, suggesting that the yak biceps femoris has lower fatty acid oxidation capacity and greater glycolytic metabolic potential.
Assuntos
Bovinos/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Genes Mitocondriais/genética , Mitocôndrias Musculares/enzimologia , Músculo Esquelético/enzimologia , Cadeias Pesadas de Miosina/genética , 3-Hidroxiacil-CoA Desidrogenases/genética , 3-Hidroxiacil-CoA Desidrogenases/metabolismo , Animais , Carnitina O-Palmitoiltransferase/genética , Carnitina O-Palmitoiltransferase/metabolismo , Canais Iônicos/genética , Canais Iônicos/metabolismo , Isocitrato Desidrogenase/genética , Isocitrato Desidrogenase/metabolismo , Masculino , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Cadeias Pesadas de Miosina/metabolismo , Prostaglandina-Endoperóxido Sintases/genética , Prostaglandina-Endoperóxido Sintases/metabolismo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteína Desacopladora 3RESUMO
Decreased levels of estrogen are associated with hepatic steatosis (HS), through changes in gene expression of molecules related to fat oxidation and lipogenesis. Both resistance training (RT) and endurance training (ET) prevent HS in ovariectomized (Ovx) rats. However, the molecular events associated with this process were only investigated for ET, but not for RT. Thus, the aim of this study was to investigate the effects of Ovx and RT on the gene expression of molecules related to fat oxidation and lipogenesis in the liver of rats. Sprague-Dawley adult female rats were grouped into four (n = 6 per group): sham-operated sedentary (Sham-Sed); Ovx sedentary (Ovx-Sed); sham-Rt and Ovx-Rt. A 10-week RT period, during which the animals climbed a 1.1-m vertical ladder with weights attached to their tails, was used. The sessions were performed three times a week, with 4-9 climbs and 8-12 dynamic movements per climb. Gene expression was analyzed by RT-PCR by the ∆∆Ct method. The estrogen deficiency associated with ovariectomy decreased the gene expression of molecules related to fat oxidation, carnitine palmitoyltransferase I (53%) and ß-hydroxyacyl-CoA dehydrogenase (27%), and increased molecules related to lipogenesis, sterol regulatory element-binding protein-1c (106%), acetyl-CoA carboxylase (ACC) (72%) and stearoyl CoA desaturase-1 (109%). With the exception of ACC, the ovariectomy-induced changes in the expression of these molecules were restored by RT. The present results indicate that RT has important effects on the prevention of HS in Ovx animals, through changes in gene expression of molecules related to hepatic lipid metabolism.
Assuntos
Fígado Gorduroso/prevenção & controle , Metabolismo dos Lipídeos , Lipogênese , Fígado/metabolismo , Contração Muscular , Músculo Esquelético/metabolismo , Ovariectomia , Treinamento Resistido , 3-Hidroxiacil-CoA Desidrogenases/genética , 3-Hidroxiacil-CoA Desidrogenases/metabolismo , Acetil-CoA Carboxilase/genética , Acetil-CoA Carboxilase/metabolismo , Animais , Carnitina O-Palmitoiltransferase/genética , Carnitina O-Palmitoiltransferase/metabolismo , Estrogênios/deficiência , Fígado Gorduroso/genética , Fígado Gorduroso/metabolismo , Feminino , Regulação da Expressão Gênica , Metabolismo dos Lipídeos/genética , Lipogênese/genética , Oxirredução , PPAR alfa/genética , PPAR alfa/metabolismo , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Estearoil-CoA Dessaturase/genética , Estearoil-CoA Dessaturase/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Fatores de TempoAssuntos
Transportadores de Cassetes de Ligação de ATP/genética , Hiperinsulinismo Congênito/genética , Hipoglicemia/etiologia , Canais de Potássio Corretores do Fluxo de Internalização/genética , Canais de Potássio/genética , Proteínas/efeitos adversos , Receptores de Droga/genética , 3-Hidroxiacil-CoA Desidrogenases/genética , Transportadores de Cassetes de Ligação de ATP/metabolismo , Trifosfato de Adenosina/metabolismo , Criança , Humanos , Hipoglicemia/metabolismo , Lactente , Mutação , Canais de Potássio/metabolismo , Canais de Potássio Corretores do Fluxo de Internalização/metabolismo , Receptores de Droga/metabolismo , Receptores de SulfonilureiasRESUMO
Fatty acids play an important role in regulating insulin secretion, but the mechanisms are unclear. We report a case of a novel splice site mutation in the short-chain 3-hydroxyacyl-CoA dehydrogenase (SCHAD) gene associated with hyperinsulinism. This mutation resulted in a nearly complete absence of immunoreactive protein and a decrease in fibroblast SCHAD activity.
Assuntos
3-Hidroxiacil-CoA Desidrogenases/genética , Hiperinsulinismo/genética , 3-Hidroxiacil-CoA Desidrogenases/metabolismo , Clorotiazida/uso terapêutico , Diazóxido/uso terapêutico , Diuréticos , Humanos , Hiperinsulinismo/tratamento farmacológico , Lactente , Masculino , Mutação Puntual , Inibidores de Simportadores de Cloreto de Sódio/uso terapêuticoRESUMO
Fetal abnormalities including chylous ascites, polyhydramnios, claw hands, and hammer toes were identified in an infant who had a missense mutation R106P and a 52bp deletion in the gene for a peroxisomal beta-oxidation enzyme, D-3-hydroxyacyl-CoA dehydratase/D-3-hydroxyacyl-CoA dehydrogenase, D-bifunctional protein. The patient had psychomotor retardation and craniofacial dysmorphism and died at 7 months of age. The patient had atypical fetal manifestations of this enzyme deficiency.
Assuntos
17-Hidroxiesteroide Desidrogenases , 3-Hidroxiacil-CoA Desidrogenases/deficiência , Ascite Quilosa/congênito , Ascite Quilosa/complicações , Contratura/congênito , Contratura/complicações , Enoil-CoA Hidratase , Deformidades Congênitas do Pé/complicações , Deformidades Congênitas da Mão/complicações , Hidroliases/deficiência , Complexos Multienzimáticos/deficiência , Poli-Hidrâmnios/complicações , 3-Hidroxiacil-CoA Desidrogenases/genética , Ascite Quilosa/genética , Contratura/genética , Evolução Fatal , Feminino , Deformidades Congênitas do Pé/genética , Deleção de Genes , Deformidades Congênitas da Mão/genética , Humanos , Hidroliases/genética , Lactente , Recém-Nascido , Masculino , Complexos Multienzimáticos/genética , Mutação de Sentido Incorreto/genética , Proteína Multifuncional do Peroxissomo-2 , GravidezRESUMO
We describe a case of liver-specific short-chain hydroxyacyl-coenzyme A dehydrogenase deficiency. Enzymatic confirmation of heterozygosity was shown in family members, illustrating the recessive nature of this new disorder. Heterozygous carriers did not present with biochemical abnormalities when challenged by fasting.
Assuntos
3-Hidroxiacil-CoA Desidrogenases/deficiência , Erros Inatos do Metabolismo/diagnóstico , Morte Súbita do Lactente/diagnóstico , 3-Hidroxiacil-CoA Desidrogenases/genética , Pré-Escolar , Feminino , Heterozigoto , Humanos , Lactente , Recém-Nascido , Fígado/enzimologia , Fígado/patologia , Masculino , Erros Inatos do Metabolismo/genéticaRESUMO
Azotobacter vinelandii is proposed to contain a single beta-ketothiolase activity participating in the formation of acetoacetyl-CoA, a precursor for poly-beta-hydroxybutyrate (PHB) synthesis, and in beta-oxidation (Manchak, J., Page, W.J., 1994. Control of polyhydroxyalkanoate synthesis in Azotobacter vinelandii strain UWD. Microbiology 140, 953-963). We designed a degenerate oligonucleotide from a highly conserved region among bacterial beta-ketothiolases and used it to identify bktA, a gene with a deduced protein product with a high similarity to beta-ketothiolases. Immediately downstream of bktA, we identified a gene called hbdH, which encodes a protein exhibiting similarity to beta-hydroxyacyl-CoA and beta-hydroxybutyryl-CoA dehydrogenases. Two regions with homology to bktA were also observed. One of these was cloned and allowed the identification of the phbA gene, encoding a second beta-ketothiolase. Strains EV132, EV133, and GM1 carrying bktA, hbdH and phbA mutations, respectively, as well as strain EG1 carrying both bktA and phbA mutations, were constructed. The hbdH mutation had no effect on beta-hydroxybutyryl-CoA dehydrogenase activity or on fatty acid assimilation. The bktA mutation had no effect on beta-ketothiolase activity, PHB synthesis or fatty acid assimilation, whereas the phbA mutation significantly reduced beta-ketothiolase activity and PHB accumulation, showing that this is the beta-ketothiolase involved in PHB biosynthesis. Strain EG1 was found to grow under beta-oxidation conditions and to possess beta-ketothiolase activity. Taken together, these results demonstrate the presence of three genes coding for beta-ketothiolases in A. vinelandii.
Assuntos
Acetil-CoA C-Aciltransferase/genética , Azotobacter vinelandii/genética , 3-Hidroxiacil-CoA Desidrogenases/genética , 3-Hidroxiacil-CoA Desidrogenases/metabolismo , Acetil-CoA C-Aciltransferase/metabolismo , Sequência de Aminoácidos , Azotobacter vinelandii/enzimologia , Azotobacter vinelandii/metabolismo , Divisão Celular/efeitos dos fármacos , Divisão Celular/genética , Clonagem Molecular , DNA Bacteriano/química , DNA Bacteriano/genética , Ácidos Graxos/farmacologia , Genes Bacterianos/genética , Genótipo , Hidroxibutiratos/metabolismo , Dados de Sequência Molecular , Mutação , Oxirredução , Poliésteres/metabolismo , Alinhamento de Sequência , Análise de Sequência de DNA , Homologia de Sequência de AminoácidosRESUMO
Mitochondrial trifunctional protein (MTP), an enzyme complex participating in fatty acid beta-oxidation, is the potential site of two documented defects: long-chain 3-hydroxyacyl-coenzyme A dehydrogenase (LCHAD) and MTP deficiencies. LCHAD deficiency usually manifests as hypoglycemia, with hepatopathy, hypotonia, cardiomyopathy, and retinopathy. Hypoparathyroidism has been detected in a patient with MTP deficiency. We now report on a patient with LCHAD deficiency and hypoparathyroidism, evidenced by hypocalcemia, hyperphosphatemia, and a low level of parathyroid hormone, in whom the parathyroid glands could not be located after death.