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1.
PLoS One ; 16(2): e0247683, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33621267

RESUMO

Essential fructosuria (EF) is a benign, asymptomatic, autosomal recessive condition caused by loss-of-function variants in the ketohexokinase gene and characterized by intermittent appearance of fructose in the urine. Despite a basic understanding of the genetic and molecular basis of EF, relatively little is known about the long-term clinical consequences of ketohexokinase gene variants. We examined the frequency of ketohexokinase variants in the UK Biobank sample and compared the cardiometabolic profiles of groups of individuals with and without these variants alone or in combination. Study cohorts consisted of groups of participants defined based on the presence of one or more of the five ketohexokinase gene variants tested for in the Affymetrix assays used by the UK Biobank. The rs2304681:G>A (p.Val49Ile) variant was present on more than one-third (36.8%) of chromosomes; other variant alleles were rare (<1%). No participants with the compound heterozygous genotype present in subjects exhibiting the EF phenotype in the literature (Gly40Arg/Ala43Thr) were identified. The rs2304681:G>A (p.Val49Ile), rs41288797 (p.Val188Met), and rs114353144 (p.Val264Ile) variants were more common in white versus non-white participants. Otherwise, few statistically or clinically significant differences were observed after adjustment for multiple comparisons. These findings reinforce the current understanding of EF as a rare, benign, autosomal recessive condition.


Assuntos
Alelos , Frutoquinases/genética , Variação Genética , Idoso , Bancos de Espécimes Biológicos , Feminino , Frutoquinases/deficiência , Erros Inatos do Metabolismo da Frutose , Genótipo , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Reino Unido
2.
Endocrinol. diabetes nutr. (Ed. impr.) ; 67(4): 253-262, abr. 2020. ilus, graf, tab
Artigo em Espanhol | IBECS | ID: ibc-194793

RESUMO

INTRODUCCIÓN: La intolerancia hereditaria a la fructosa es una enfermedad metabólica debida a una deficiencia en la aldolasa B. Nuestro objetivo es conocer las necesidades sociosanitarias del colectivo. METODOLOGÍA: Estudio observacional prospectivo en el que se difundió una encuesta de necesidades sociosanitarias a pacientes con intolerancia hereditaria a la fructosa residentes en España. RESULTADOS: La mayoría disponían de diagnóstico, confirmado principalmente por análisis genético en menores y sobrecarga de fructosa en adultos, no padecían secuelas (72,34%) ni discapacidad (64%) y el 83,33% de niños tomaban medicamentos frente al 52,38% de adultos (p < 0,05) (2,06 medicamentos de media). La mayoría acudieron a consultas en los dos últimos años, principalmente unidades de enfermedades metabólicas (42,5%) y/o nutricionista (42,5%), aunque menos de la mitad eran atendidos en centros de referencia (mayoritariamente niños [p < 0,05]). El 48% estaban satisfechos con la atención sanitaria aunque se sintieron discriminados en actividades de ocio, escolares, sanitarias y/o cotidianas. Las fuentes más fiables de información fueron el médico de atención especializada (69,39%) y la asociación de pacientes (59,18%). El 54% no indicaron ningún problema en ninguna de las dimensiones de calidad de vida, aunque algunos tuvieron problemas en actividades cotidianas, dolor y ansiedad. CONCLUSIONES: Aunque su perfil no sea tan discapacitante como el de otras enfermedades raras, es importante conocer las necesidades del paciente con intolerancia hereditaria a la fructosa. Aunque se han reducido los tiempos en el diagnóstico, la menor atención y satisfacción sanitaria en adultos hace necesario incidir en las necesidades de esta población, siendo clave la formación e información de los profesionales sanitarios


INTRODUCTION: Hereditary fructose intolerance is a metabolic disease due to an aldolase B deficiency. Our objective was to ascertain the social and health care needs of those with this deficiency. MATERIAL AND METHODS: A prospective, observational study was performed. A survey of social and health care needs was conducted to hereditary fructose intolerance patients living in Spain. RESULTS: Most patients had been diagnosed, mainly by genetic analysis in children and based on fructose overload in adults. Population surveyed had no sequelae (72.34%) or disability (64%), and 83.33% of children and 52.38% of adults were taking drugs (p < .05) (2.06 drugs on average). Most patients had attended medical visits in the past two years, mainly in metabolic disease units (42.5%) and/or nutrition units (42.5%), but less than a half attended reference centers (mostly children [p < 0.05]). Although 48% were satisfied with health care, they felt discriminated in recreational activities, school, health and/or daily activities. The most reliable sources of information were the specialized care physician (69.39%) and patients' association (59.18%). Fifty-five percent reported no problem in any quality of life dimension, although some had problems in daily activities, pain, and anxiety. CONCLUSIONS: Although hereditary fructose intolerance is less disabling than other rare diseases, it is important to know the needs of those who suffer from it. Although time to diagnosis has shortened, the poorer health care and satisfaction with it perceived in adults makes it necessary to emphasize the needs of this population, and the critical need of training and information of health care professionals


Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto Jovem , Erros Inatos do Metabolismo da Frutose , Intolerância à Frutose , Determinação de Necessidades de Cuidados de Saúde , Inquéritos e Questionários , Estudos Prospectivos , Doenças Raras , Espanha
3.
Dig Dis Sci ; 65(5): 1405-1413, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31617133

RESUMO

BACKGROUND: Unexplained bloating, gas, and pain are common symptoms. If routine tests are negative, such patients are often labeled as irritable bowel syndrome. AIMS: To determine the diagnostic utility of breath tests that assess for small intestinal bacterial overgrowth (SIBO), fructose or lactose intolerance, and the predictive value of symptoms. METHODS: Patients with gas, bloating, diarrhea, abdominal pain (≥ 6 months), and negative endoscopy and radiology tests were assessed with symptom questionnaires, glucose (75 g), fructose (25 g), or lactose (25 g) breath tests. Breath tests were categorized as positive when H2 (≥ 20 ppm) or CH4 (≥ 15 ppm) increased above baseline values or as hypersensitive when symptoms changed significantly without rise in H2/CH4 or as negative. RESULTS: 1230 patients (females = 878) underwent 2236 breath tests. The prevalence of SIBO was 33% (294/883), fructose intolerance was 34% (262/763), and lactose intolerance was 44% (260/590). Hypersensitivity was found in 16% and 9%, respectively, during fructose and lactose breath tests. Although gas (89%), abdominal pain (82%), and bloating (82%) were highly prevalent, pretest symptoms or their severity did not predict an abnormal breath test, but symptoms during the breath test facilitated diagnosis of SIBO, fructose, and lactose intolerance and hypersensitivity. CONCLUSIONS: Approximately 45% of patients with unexplained gas and bloating had SIBO, fructose, or lactose intolerance; another 9-16% had visceral hypersensitivity. Pretest symptoms were poor predictors, but symptoms during the breath tests were useful. Breath tests are safe, provide significant diagnostic yield, and could be useful in routine gastroenterology practice.


Assuntos
Síndrome da Alça Cega/diagnóstico , Testes Respiratórios/métodos , Carboidratos/análise , Erros Inatos do Metabolismo da Frutose/diagnóstico , Intolerância à Lactose/diagnóstico , Adulto , Síndrome da Alça Cega/epidemiologia , Diagnóstico Diferencial , Feminino , Frutose/análise , Erros Inatos do Metabolismo da Frutose/epidemiologia , Glucose/análise , Humanos , Lactose/análise , Intolerância à Lactose/epidemiologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prevalência
4.
Nutrients ; 11(12)2019 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-31888122

RESUMO

Intolerance to lactose or fructose is frequently diagnosed in children with chronic abdominal pain (CAP). However, the causal relationship remains a matter of discussion. A cohort of 253 patients, aged 7-12 years, presenting with unexplained CAP received standardized diagnostics. Additional diagnostic tests were performed based on their medical history and physical and laboratory investigations. Fructose and lactose hydrogen breath tests (H2BT) as well as empiric diagnostic elimination diets were performed in 135 patients reporting abdominal pain related to the consumption of lactose or fructose to evaluate carbohydrate intolerance as a potential cause of CAP. Carbohydrate malabsorption by H2BT was found in 55 (41%) out of 135 patients. An abnormal increase in H2BT was revealed in 30% (35/118) of patients after fructose consumption and in 18% (20/114) of patients after lactose administration. Forty-six percent (25/54) reported pain relief during a diagnostic elimination diet. In total, 17 patients had lactose malabsorption, 29 fructose malabsorption, and nine combined carbohydrate malabsorption. Carbohydrate intolerance as a cause of CAP was diagnosed at follow-up in only 18% (10/55) of patients with malabsorption after the elimination of the respective carbohydrate. Thus, carbohydrate malabsorption appears to be an incidental finding in children with functional abdominal pain disorders, rather than its cause. Therefore, testing of carbohydrate intolerance should only be considered in children with a strong clinical suspicion and with the goal to prevent long-term unnecessary dietary restrictions in children suffering from CAP.


Assuntos
Dor Abdominal/diagnóstico , Erros Inatos do Metabolismo dos Carboidratos/diagnóstico , Dor Crônica/diagnóstico , Erros Inatos do Metabolismo da Frutose/diagnóstico , Intolerância à Lactose/diagnóstico , Síndromes de Malabsorção/diagnóstico , Dor Abdominal/etiologia , Testes Respiratórios , Erros Inatos do Metabolismo dos Carboidratos/complicações , Criança , Dor Crônica/etiologia , Diagnóstico Diferencial , Feminino , Frutose/análise , Erros Inatos do Metabolismo da Frutose/complicações , Humanos , Lactose/análise , Intolerância à Lactose/complicações , Síndromes de Malabsorção/complicações , Masculino
5.
Am J Physiol Endocrinol Metab ; 315(3): E386-E393, 2018 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-29870677

RESUMO

Fructose consumption in humans and animals has been linked to enhanced de novo lipogenesis, dyslipidemia, and insulin resistance. Hereditary deficiency of ketohexokinase (KHK), the first enzymatic step in fructose metabolism, leads to essential fructosuria in humans, characterized by elevated levels of blood and urinary fructose following fructose ingestion but is otherwise clinically benign. To address whether KHK deficiency is associated with altered glucose and lipid metabolism, a Khk knockout (KO) mouse line was generated and characterized. NMR spectroscopic analysis of plasma following ingestion of [6-13C] fructose revealed striking differences in biomarkers of fructose metabolism. Significantly elevated urine and plasma 13C-fructose levels were observed in Khk KO vs. wild-type (WT) control mice, as was reduced conversion of 13C-fructose into plasma 13C-glucose and 13C-lactate. In addition, the observation of significant levels of fructose-6-phosphate in skeletal muscle tissue of Khk KO, but not WT, mice suggests a potential mechanism, whereby fructose is metabolized via muscle hexokinase in the absence of KHK. Khk KO mice on a standard chow diet displayed no metabolic abnormalities with respect to ambient glucose, glucose tolerance, body weight, food intake, and circulating trigylcerides, ß-hydroxybutyrate, and lactate. When placed on a high-fat and high-fructose (HF/HFruc) diet, Khk KO mice had markedly reduced liver weight, triglyceride levels, and insulin levels. Together, these results suggest that Khk KO mice may serve as a good model for essential fructosuria in humans and that inhibition of KHK offers the potential to protect from diet-induced hepatic steatosis and insulin resistance.


Assuntos
Dieta , Frutoquinases/deficiência , Erros Inatos do Metabolismo da Frutose/genética , Doenças Metabólicas/genética , Doenças Metabólicas/metabolismo , Animais , Glicemia/metabolismo , Peso Corporal/genética , Dieta Hiperlipídica , Ingestão de Alimentos/genética , Frutoquinases/genética , Frutoquinases/metabolismo , Erros Inatos do Metabolismo da Frutose/metabolismo , Frutosefosfatos/sangue , Intolerância à Glucose/genética , Resistência à Insulina , Metabolismo dos Lipídeos/genética , Camundongos Knockout
6.
Am J Physiol Endocrinol Metab ; 315(3): E394-E403, 2018 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-29664676

RESUMO

Fructose is a major component of Western diets and is implicated in the pathogenesis of obesity and type 2 diabetes. In response to an oral challenge, the majority of fructose is cleared during "first-pass" liver metabolism, primarily via phosphorylation by ketohexokinase (KHK). A rare benign genetic deficiency in KHK, called essential fructosuria (EF), leads to altered fructose metabolism. The only reported symptom of EF is the appearance of fructose in the urine following either oral or intravenous fructose administration. Here we develop and use a mathematical model to investigate the adaptations to altered fructose metabolism in people with EF. First, the model is calibrated to fit available data in normal healthy subjects. Then, to mathematically represent EF subjects, we systematically implement metabolic adaptations such that model simulations match available data for this phenotype. We hypothesize that these modifications represent the major metabolic adaptations present in these subjects. This modeling approach suggests that several other aspects of fructose metabolism, beyond hepatic KHK deficiency, are altered and contribute to the etiology of this benign condition. Specifically, we predict that fructose absorption into the portal vein is altered, peripheral metabolism is slowed, renal reabsorption of fructose is mostly ablated, and alternate pathways for hepatic metabolism of fructose are upregulated. Moreover, these findings have implications for drug discovery and development, suggesting that the therapeutic targeting of fructose metabolism could lead to unexpected metabolic adaptations, potentially due to a physiological response to high-fructose conditions.


Assuntos
Frutoquinases/deficiência , Erros Inatos do Metabolismo da Frutose/metabolismo , Frutose/metabolismo , Adaptação Fisiológica , Algoritmos , Simulação por Computador , Diabetes Mellitus Tipo 2 , Frutoquinases/metabolismo , Erros Inatos do Metabolismo da Frutose/enzimologia , Voluntários Saudáveis , Humanos , Fígado/metabolismo , Modelos Teóricos
8.
Nutrients ; 9(4)2017 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-28368361

RESUMO

Fructose is one of the main sweetening agents in the human diet and its ingestion is increasing globally. Dietary sugar has particular effects on those whose capacity to metabolize fructose is limited. If intolerance to carbohydrates is a frequent finding in children, inborn errors of carbohydrate metabolism are rare conditions. Three inborn errors are known in the pathway of fructose metabolism; (1) essential or benign fructosuria due to fructokinase deficiency; (2) hereditary fructose intolerance; and (3) fructose-1,6-bisphosphatase deficiency. In this review the focus is set on the description of the clinical symptoms and biochemical anomalies in the three inborn errors of metabolism. The potential toxic effects of fructose in healthy humans also are discussed. Studies conducted in patients with inborn errors of fructose metabolism helped to understand fructose metabolism and its potential toxicity in healthy human. Influence of fructose on the glycolytic pathway and on purine catabolism is the cause of hypoglycemia, lactic acidosis and hyperuricemia. The discovery that fructose-mediated generation of uric acid may have a causal role in diabetes and obesity provided new understandings into pathogenesis for these frequent diseases.


Assuntos
Metabolismo Energético , Medicina Baseada em Evidências , Erros Inatos do Metabolismo da Frutose/fisiopatologia , Frutose/efeitos adversos , Modelos Biológicos , Adoçantes Calóricos/efeitos adversos , Animais , Frutose/metabolismo , Erros Inatos do Metabolismo da Frutose/enzimologia , Erros Inatos do Metabolismo da Frutose/metabolismo , Humanos , Adoçantes Calóricos/metabolismo
10.
Acta Paediatr ; 101(9): e411-5, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22578243

RESUMO

AIM: To investigate malabsorption of lactose and fructose as causes of recurrent abdominal pain (RAP). METHODS: In 220 children (128 girls, mean age 8,8 [4.1-16.0] years) with RAP, hydrogen breath tests (H(2) BT; abnormal if ΔH(2) > 30 ppm) were performed with lactose and fructose. Disappearance of RAP with elimination, recurrence with provocation and disappearance with re-elimination, followed by a 6-month pain-free follow-up, were considered indicative of a causal relation with RAP. For definite proof, a double-blinded placebo-controlled (DBPC) provocation was performed. RESULTS: Malabsorption of lactose was found in 57 of 210, of fructose in 79 of 121 patients. Pain disappeared upon elimination in 24/38 patients with lactose malabsorption, and in 32/49 with fructose malabsorption. Open provocation with lactose and fructose was positive in 7/23 and 13/31 patients. DBPC provocation in 6/7 and 8/13 patients was negative in all. However, several children continued to report abdominal symptoms upon intake of milk or fructose. CONCLUSION: Lactose intolerance nor fructose intolerance could be established as causes of RAP, according to preset criteria including elimination, open provocation and DBPC provocation. However, in clinical practice, persistent feeling of intolerance in some patients should be taken seriously and could warrant extended elimination with repeated challenges.


Assuntos
Dor Abdominal/etiologia , Erros Inatos do Metabolismo da Frutose/complicações , Intolerância à Lactose/complicações , Dor Abdominal/metabolismo , Adolescente , Testes Respiratórios , Criança , Pré-Escolar , Doença Crônica , Método Duplo-Cego , Feminino , Erros Inatos do Metabolismo da Frutose/metabolismo , Humanos , Hidrogênio/metabolismo , Intolerância à Lactose/metabolismo , Masculino , Recidiva
11.
Best Pract Res Clin Gastroenterol ; 24(5): 607-18, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20955963

RESUMO

Glycogen storage diseases (GSD) and inborn errors of galactose and fructose metabolism are the most common representatives of inborn errors of carbohydrate metabolism. In this review the focus is set on the current knowledge about clinical symptoms, diagnosis and treatment. Hepatomegaly and hypoglycaemia are the main findings in liver-affecting GSD like type I, III and IX. Diagnosis is usually made by non invasive investigations, e.g. mutation analysis. In GSD I, a carbohydrate balanced diet with frequent meals and nocturnal continuous tube feeding or addition of uncooked corn starch are the mainstays of treatment to prevent hypoglycaemia. Liver transplantation has been performed in different types of GSD. It should only be considered in high risk patients e.g. with substantial cirrhosis. Many countries have included classical galactosaemia in their newborn screening programs. A lactose-free infant formula can be life-saving in affected neonates whereas a strict fructose-restricted diet is indicated in hereditary fructose intolerance.


Assuntos
Erros Inatos do Metabolismo da Frutose/diagnóstico , Erros Inatos do Metabolismo da Frutose/terapia , Galactosemias/diagnóstico , Galactosemias/terapia , Doença de Depósito de Glicogênio/diagnóstico , Doença de Depósito de Glicogênio/terapia , Adulto , Criança , Carboidratos da Dieta/administração & dosagem , Intolerância à Frutose/diagnóstico , Intolerância à Frutose/terapia , Deficiência de Frutose-1,6-Difosfatase/diagnóstico , Deficiência de Frutose-1,6-Difosfatase/terapia , Galactose/metabolismo , Doença de Depósito de Glicogênio/classificação , Doença de Depósito de Glicogênio/genética , Humanos , Lactente , Hepatopatias/classificação , Hepatopatias/diagnóstico , Hepatopatias/genética , Transplante de Fígado , Prognóstico
13.
Clin Chim Acta ; 401(1-2): 81-3, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19100247

RESUMO

BACKGROUND: Variable increases in the plasma activity of different lysosomal enzymes have been reported in patients with congenital disorders of glycosylation (CDG). In particular, elevated plasma aspartylglucosaminidase activity (AGA) has been found in the majority of CDG type I patients. We report on the plasma activity of AGA and other lysosomal enzymes in patients with different types of primary and secondary CDG defects. METHODS: AGA, alpha-mannosidase, beta-mannosidase and beta-hexosaminidase activities were assayed in the plasma of patients with CDGI (4CDGIa, 4CDGIx) and CDGIIx (5, all with a combined N- and O-glycosylation defect), classical galactosemia (GALT) (n=3) and hereditary fructose intolerance (HFI) (n=2). RESULTS: Increased AGA and beta-hexosaminidase activities were found in all and 7/8 of the GDGI patients respectively. All enzymic activities were normal in the CDGIIx patients. Elevated AGA and beta-hexosaminidase activity was also seen in GALT and HFI patients before treatment, when transferrin isoelectric focusing (TfIEF) patterns were also abnormal. CONCLUSIONS: Increased AGA plasma activity, although a consistent finding in CDGI patients, is not specific to this group of disorders since it is also observed in untreated cases of GALT and HFI. Furthermore, plasma AGA activity cannot serve as a marker for CDGII disorders. In conjunction with TfIEF it could be used in the follow up of GALT and HFI patients.


Assuntos
Aspartilglucosilaminase/sangue , Erros Inatos do Metabolismo da Frutose/enzimologia , Galactosemias/enzimologia , Adolescente , Criança , Pré-Escolar , Intolerância à Frutose/sangue , Intolerância à Frutose/diagnóstico , Intolerância à Frutose/enzimologia , Erros Inatos do Metabolismo da Frutose/sangue , Erros Inatos do Metabolismo da Frutose/diagnóstico , Galactosemias/sangue , Glicosilação , Humanos , Lactente , Lisossomos/enzimologia , alfa-Manosidase/sangue , beta-Manosidase/sangue , beta-N-Acetil-Hexosaminidases/sangue
14.
Clin Gastroenterol Hepatol ; 4(5): 635-8, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16630753

RESUMO

BACKGROUND & AIMS: Celiac disease (CD) has been associated with several genetic disorders, but has not been associated with hereditary fructose intolerance (HFI). METHODS: We identified CD in 4 female patients affected by HFI from among 38 Italian HFI patients. RESULTS: Three of these patients were children in whom the CD-associated signs were hypertransaminasemia, failure to thrive, low weight, and short stature, whereas the adult patient had protracted diarrhea notwithstanding a fructose-free diet. The incidence of CD in our group of HFI patients was higher (>10%) than in the general population (1%-3%) (P<.02). CONCLUSIONS: The possibility of an association between these 2 gastrointestinal disorders is important, particularly in the management of HFI patients with persisting symptoms.


Assuntos
Doença Celíaca/complicações , Doença Celíaca/diagnóstico , Intolerância à Frutose/complicações , Intolerância à Frutose/genética , Predisposição Genética para Doença , Mutação , Adulto , Fatores Etários , Criança , Pré-Escolar , Feminino , Seguimentos , Intolerância à Frutose/diagnóstico , Erros Inatos do Metabolismo da Frutose/complicações , Erros Inatos do Metabolismo da Frutose/diagnóstico , Erros Inatos do Metabolismo da Frutose/genética , Antígenos HLA-DQ/genética , Antígenos HLA-DR/genética , Humanos , Incidência , Itália/epidemiologia , Linhagem , Estudos Retrospectivos , Medição de Risco , Amostragem , Índice de Gravidade de Doença
15.
Rev. nutr ; 18(3): 377-389, maio-jun. 2005. ilus, tab
Artigo em Português | LILACS | ID: lil-415968

RESUMO

Revisa-se o metabolismo da frutose e do sorbitol, suas principais indicações e conseqüências decorrentes do uso inadequado. A frutose é um importante carboidrato da dieta, sendo encontrada principalmente nas frutas e vegetais, e é produzida no organismo a partir da glicose pela via do sorbitol. A frutose é conhecida pelos erros inatos do seu metabolismo, cujas manifestações clínicas são potencialmente graves, e por seu uso como substituta da glicose na dieta de diabéticos, visto não depender da insulina para o seu metabolismo. Nos últimos anos, especialmente em países desenvolvidos, seu consumo tem aumentado acentuadamente em virtude do emprego como adoçante em produtos industrializados. Porém, o uso excessivo de frutose não é isento de efeitos adversos, representados pelo aumento de triglicerídios e de colesterol no sangue. O conhecimento dos níveis sangüíneos normais é importante tanto para estabelecer a quantidade segura a ser administrada, como para permitir avaliar doenças metabólicas associadas à frutose.


Assuntos
Frutose , Erros Inatos do Metabolismo da Frutose , Sorbitol
17.
Diabetes ; 52(9): 2426-32, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12941785

RESUMO

Alternative splicing of the ketohexokinase (fructokinase) gene generates a "central" predominantly hepatic isoform (ketohexokinase-C) and a more widely distributed ketohexokinase-A. Only the abundant hepatic isoform is known to possess activity, and no function is defined for the lower levels of ketohexokinase-A in peripheral tissues. Hepatic ketohexokinase deficiency causes the benign disorder essential fructosuria. The molecular basis of this has been defined in one family (compound heterozygosity for mutations Gly40Arg and Ala43Thr). Here we show that both ketohexokinase isoforms are indeed active. Ketohexokinase-A has much poorer substrate affinity than ketohexokinase-C for fructose but is considerably more thermostable. The Gly40Arg mutation seems null, rendering both ketohexokinase-A and ketohexokinase-C inactive and largely insoluble. The Ala43Thr mutant retains activity, but this mutation decreases the thermal stability of both ketohexokinase-A and ketohexokinase-C. At physiologic temperature, this results in significant loss of ketohexokinase-C activity but not of ketohexokinase-A. Affected individuals who carry both mutations therefore probably have a selective deficiency of hepatic ketohexokinase, with peripheral ketohexokinase-A being preserved. These findings raise the possibility that ketohexokinase-A serves an unknown physiologic function that remains intact in essential fructosuria. Further mutation analysis in this rare disorder could illuminate the question of whether ketohexokinase-A activity is, unlike that of ketohexokinase-C, physiologically indispensable.


Assuntos
Frutoquinases/genética , Frutoquinases/metabolismo , Erros Inatos do Metabolismo da Frutose/enzimologia , Erros Inatos do Metabolismo da Frutose/genética , Frutose/urina , Processamento Alternativo , Escherichia coli , Erros Inatos do Metabolismo da Frutose/urina , Regulação Enzimológica da Expressão Gênica , Temperatura Alta , Humanos , Cinética , Proteínas Recombinantes/genética , Especificidade por Substrato
18.
Acta pediatr. esp ; 59(8): 424-435, sept. 2001. tab, graf
Artigo em Es | IBECS | ID: ibc-9950

RESUMO

El tratamiento nutricional de los errores innatos del metabolismo constituye en la actualidad el pilar más importante en el manejo global de estas enfermedades. Las intervenciones dietéticas no sólo deben intentar asegurar un adecuado crecimiento y desarrollo del niño, sino que, al mismo tiempo, se debe programar un enfoque nutricional específico según el defecto metabólico del que se trate. En este artículo -primero de dos partes- se abordan los aspectos dietéticos y nutricionales del los trastornos más frecuentes que afectan al metabolismo de los hidratos de carbono y de las grasas (betaoxidación) (AU)


Assuntos
Feminino , Masculino , Humanos , Erros Inatos do Metabolismo/dietoterapia , Erros Inatos do Metabolismo dos Carboidratos/dietoterapia , Erros Inatos do Metabolismo Lipídico/dietoterapia , Gorduras na Dieta/metabolismo , Carboidratos da Dieta/metabolismo , Galactose/metabolismo , Frutose/metabolismo , Erros Inatos do Metabolismo da Frutose/dietoterapia
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