Regulatory effects and mechanisms of branched chain amino acids and metabolic intermediates on insulin resistance / 生理学报

Branched chain amino acids, as essential amino acids, can be used to synthesize nitrogen-containing compounds and also act as signal molecules to regulate substance metabolism. Studies have shown that the elevated level of branched chain amino acids is closely related to insulin resistance and type 2 diabetes. It can affect insulin signal transduction by activating mammalian target of rapamycin (mTOR) signal pathway, and regulate insulin resistance by damaging lipid metabolism and affecting mitochondrial function. In addition, abnormal catabolism of branched amino acids can lead to the accumulation of metabolic intermediates, such as branched chain α-keto acids, 3-hydroxyisobutyrate and β-aminoisobutyric acid. Branched chain α-keto acids and 3-hydroxyisobutyrate can induce insulin resistance by affecting insulin signaling pathway and damaging lipid metabolism. β-aminoisobutyric acid can improve insulin resistance by reducing lipid accumulation and inflammatory reaction and enhancing fatty acid oxidation. This paper systematically reviewed the regulatory effects and mechanisms of branched chain amino acids and their metabolic intermediates on insulin resistance, which will provide a new direction for the prevention and treatment of insulin resistance and type 2 diabetes.

Recent advances in enzymatic production of alpha-keto acids / 生物工程学报

Alpha-keto acid is a bifunctional organic compound containing both carboxyl and ketone groups, and widely applied in the industries of food, pharmaceutical and cosmetics. Based on the demand of eco-friendly process, safety and sustainable development, production of α-keto acids by enzymatic conversion technology has been paid more and more attention. In this article, we review the status of α-keto acids biosynthesis from three aspects: enzymatic screening, enzymatic modification and optimization of enzymatic conversion conditions. Meanwhile, we also indicate future research directions for further improving α-keto acids production.

Randomized controlled clinical trial of ketoanalogues supplementation in dogs with chronic kidney disease / Estudo clínico randomizado controlado da suplementação de cetoanálogos em cães com doença renal crônica

The objective was to verify the effectiveness of ketoanalogues in dogs with Chronic Kidney Disease (CKD) stage 3. Controlled randomized clinical trial was performed with twenty dogs with CKD stage 3. Animals were subjected to: Group 1 (control): conventional therapy (CT) for CKD; Group 2: CT and 60mg/kg, OA, q48h of keto-supplementa; Group 3, CT and 60mg/kg, OA, q24h of keto-supplementa; and Group 4, CT and 120mg/kg, OA, q12h of keto-supplementa. All dogs received canine renal diet. Animals were evaluated at the beginning of therapy and after 15 and 30 days. Complete blood count (CBC), serum urea, creatinine, phosphorus, calcium, potassium and sodium and urine protein/creatinine (UPC) ratio were analyzed. The use of ketoanalogues in dogs with CKD stage 3 during the period of 30 days showed no efficacy, in any of the studies dosages, to improve signs and symptoms of the disease, improve the values of CBC, reduce serum urea and creatinine, normalize electrolytes or reduce UPC. It is concluded that the use of ketoanalogues does not impact the clinical outcomes in dogs with CKD stage 3.(AU)

O objetivo foi de verificar a eficácia da suplementação com cetoanálogos em cães com Doença Renal Crônica (DRC) grau 3. Um ensaio clínico controlado e randomizado foi realizado com 20 cães com DRC grau 3. Os animais foram divididos em 4 grupos: grupo 1 (controle): terapia convencional (TC) para DRC; grupo 2: TC e 60mg/kg, VO, q48h de cetoanálogoa; grupo 3: TC e 60mg/kg, VO, q24h de cetoanálogoa; e grupo 4, TC e 120mg/kg, VO, q12h de cetoanálogoa. Todos os cães receberam ração renal para cães. Os animais foram avaliados no início da terapia e após 15 e 30 dias. Hemograma completo, ureia, creatinina, fósforo, cálcio, potássio e sódio séricos e a razão proteína creatinina (RPC) urinária foram analisados. Foi verificado que o uso dos cetoanálogos em cães com DRC grau 3 durante 30 dias não mostrou eficácia, em nenhuma das dosagens utilizadas, em melhorar os sinais clínicos e sintomatologia da doença, os valores do hemograma e ureia e creatinina séricos, normalizar eletrólitos e reduzir RPC. Concluiu-se que o uso de cetoanálogos não impacta na melhora de sintomatologia clínica em cães com CKD grau 3. Como esse parece ser o primeiro ensaio clínico sobre cetoanálogos em cães com CKD, mais estudos podem ser necessários com maior acompanhamento e maiores grupos.(AU)

Pruebas bioquímicas para la detección de metabolitos producidos en los errores innatos del metabolismo / Biochemical tests for the detection of metabolites produced in inborn errors of metabolism / Provas bioquímicas para a detecção de metabólitos produzidos nos erros inatos do metabolismo

Los errores innatos del metabolismo (EIM) son más de 550 enfermedades en las que se presenta una deficiencia o ausencia de proteínas con actividad enzimática, transportadora, receptora o estructural. Cada una de estas enfermedades es rara, pero su gran variedad hace que, consideradas en conjunto, sean la principal patología neonatal. Para la detección de los metabolitos producidos en los EIM se pueden utilizar pruebas cualitativas. Su utilidad radica en que son muy rápidas y de fácil acceso, y en que sirven como pruebas presuntivas para proceder a hacer exámenes más especializados o para enfocar el diagnóstico. Teniendo en cuenta su importancia para un diagnóstico temprano de los EIM, el objetivo del presente artículo es describir el funcionamiento de las pruebas bioquímicas de resorcinol, dinitrofenilhidrazina, nitrosonaftol, nitroprusiato y Hoesch, haciendo énfasis en los metabolitos que detectan.

Inborn errors of metabolism (IEM) are more than 550 diseases in which there is a deficiency or absence of proteins with enzymatic, transporter, receptor or structural activity. Individually these diseases are rare, but because of their wide variety they are, considered together, the largest neonatal disease. To detect metabolites produced in IEM qualitative tests can be used. They are easily accessible and fast to carry out, and serve as presumptive elements before proceeding to more specialized tests or to focus diagnosis. Given their importance for the early diagnosis of IEM, this article aims to describe the functioning of the following biochemical tests: dinitrophenylhydrazine, resorcinol, nitrosonaphtol, nitroprusside and Hoesch, emphasizing in the metabolites that they detect.

Os erros inatos do metabolismo (EIM) são mais de 550 doenças nas que se apresenta uma deficiência ou ausência de proteínas com atividade enzimática, transportadora, receptora ou estrutural. Cada uma destas doenças é rara, mas sua grande variedade faz que, consideradas em conjunto, sejam a principal patologia neonatal. Para a detecção dos metabólitos produzidos nos EIM se podem utilizar provas qualitativas. Sua utilidade radica em que são muito rápidas e de fácil acesso, e em que servem como provas presuntivas para proceder a fazer exames mais especializados ou para enfocar o diagnóstico. Tendo em conta sua importância para um diagnóstico precoce dos EIM, o objetivo do presente artigo é descrever o funcionamento das provas bioquímicas de resorcinol, dinitrofenilhidrazina, nitrosonaftol, nitroprusiato e Hoesch, fazendo ênfases nos metabólitos que detectam.

Effects of Keto Acids on Serum Albumin Level in Hemodialysis Patients with Hypoalbuminemia / 대한신장학회지

PURPOSE: Malnutrition is a strong predictor of increased morbidity and mortality in patients on maintenance dialysis. Although a number of studies were performed to determine effective treatment, there is no proven medication for malnutrition. This study aimed to evaluate the effect of keto acids (ketosteril(R)) on serum albumin levels in hemodialysis patients with hypoalbuminemia. METHODS: Hemodialysis patients with hypoalbumineia (serum albumin < or = 3.8 g/dL) were enrolled. Exclusion criteria were previous supplementation of keto acids before the initiation of dialysis, acute infection, liver cirrhosis, malignancy and persistent hypercalcemia. Patients were treated with ketosteril for 6 months and serum albumin levels were compared to age- and gender-matched hemodialysis patients. RESULTS: There were no significant differences in the baseline serum albumin levels between ketosteril group (n=19) and the control group (n=19). After 6 months, the mean (+/-SD) serum albumin level in the ketosteril group rose from 3.46+/-0.40 g/dL to 3.66+/-0.37 g/dL (p=0.01), but not the control group. However, the difference between the two groups was not significant (p=0.06). Multivariate analysis showed that the ketosteril supplementation (p=0.03) and the baseline serum albumin level (< or = 3.4 g/dL, p=0.04) were predictors of increased serum albumin. There was no severe hypercalcemia during the study period. CONCLUSION: There was an improvement of serum albumin levels in hemodialysis patients with hypoalbuminemia after the supplementation of keto acids.

Advances in the study of HIV-1 integrase inhibitors of alpha, gamma-diketo compounds / 药学学报

HIV-1 integrase (IN) is an essential enzyme for retroviral replication. There is no analogue for this enzyme in human cells so that inhibition of IN will not bring strong effect on human body. Thus, HIV-1 IN has become a rational target for therapy of AIDS. This review provides a comprehensive report of alpha, gamma-diketo IN inhibitors discovered in recent years. Compilation of such data will prove to be beneficial in developing QSAR, pharmacophore hypothesis generation and validation, virtual screening and synthesis of compounds with higher activity.

Effects of alpha-keto acid on the expression of neuropeptide Y in malnutrition rats with chronic renal failure / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effects of alpha-keto acid on the expression of neuropeptide Y in malnutrition rats with chronic renal failure.</p><p><b>METHODS</b>SD rats received 5/6 nephrectomy and were fed with 4% casein to establish models of malnutrition with chronic renal failure. Serum albumin, urea nitrogen, serum creatinine, type-1 insulin like growth factor and body weight of the rats were measured. The rat models were randomized into chronic renal failure group, alpha-keto acid group and normal control group, and after a 4-week treatment as indicated, neuropeptide Y mRNA levels in the hypothalamus were measured by RT-PCR in rats with surgically induced renal failure (two-stage subtotal nephrectomy). The blood neuropeptide Y of the rats were analyzed by radioimmunoassay.</p><p><b>RESULTS</b>Malnutrition occurred in chronic renal failure rats at the end of 10 weeks. Compared with those in the chronic renal failure group, the plasma neuropeptide Y concentrations in alpha-keto acid group were significantly lowered with substantially elevated neuropeptide Y mRNA expression in the hypothalamus.</p><p><b>CONCLUSION</b>alpha-keto acid capsule can improve malnutrition in rats with renal insufficiency possibly by up-regulating neuropeptide Y mRNA expression in the hypothalamus and reducing the level of blood neuropeptide Y.</p>

Enfermedad de orina en jarabe de arce: mejoría clínica asociada a detección precoz y manejo oportuno. Reporte de caso y revisión de literature / Doença de urina em xarope de arce: melhoria clínica relacionada á detecção precoce e manejo oportuno. Reporte de caso e revisão de literatura / Maple syrup urinary disease: clinical improvement associated with early detection and management. Case report and literature review

La enfermedad de orina en jarabe de arce es un error innato del metabolismo de los cetoácidos de cadena ramificada, cuya acumulación produce una encefalopatía neonatal grave y que de no ser diagnosticada y tratada de forma precoz y oportuna, lleva invariablemente a la aparición de secuelas neurológicas permanentes y a un posterior desenlace letal. El presente artículo busca, mediante la descripción de un caso clínico sucedido en el Hospital Militar Central de Bogotá, hacer una revisión de la literatura acerca de la enfermedad, resaltando los mecanismos fisiopatológicos, la detección por diferentes pruebas de laboratorio, así como las estrategias de manejo, demostrando que gracias a los progresos realizados en su comprensión y enfoque, actualmente se puede hablar de evitar la mortalidad, alcanzando en muchos casos, una sobrevida a largo plazo sin mayores secuelas neurológicas, todo ello con un manejo interdisciplinario que logre un control metabólico adecuado...

Maple syrup urine disease is an inborn error of the metabolism of branched chain keto-acids whose accumulation produces a serious neonatal encephalopathy, which if not diagnosed and treated in a precocious and opportune way, will invariably lead to the appearance of permanent neurological impairments and an ulterior lethal outcome. The present article intends, by means of the description of a clinical case which occurred at the Hospital Militar Central, to perform a review of the existent literature on this disease, to revise its fisiopathological mechanisms as well as its detection using different laboratory tests and the different care strategies, to demonstrate that, thanks to the progress achieved in its understanding and focus, at the present moment we can speak of avoiding mortality, accomplishing in many cases long term survival without important neurological consequences, all by means of an interdisciplinary approach that achieves an appropriate metabolic control...

A doença de urina em xarope de arce é um erro inato do metabolismo dos cetoácidos de corrente ramificada, cuja acumulação produz uma encefalopatia neonatal grave e que de não ser diagnosticada e tratada de forma precoce e oportuna, leva invariavelmente à aparição de seqüelas neurológicas permanentes e a um posterior desenlace letal. O presente artigo procura, mediante a descrição de um caso clínico sucedido no Hospital Militar Central de Bogotá, fazer uma revisão da literatura a respeito da doença, ressaltando os mecanismos fisiopatológicos, a detecção por diferentes provas de laboratório, bem como as estratégias de tratamento, demonstrando que graças aos progressos realizados em seu entendimento e enfoque, atualmente se pode falar de evitar a mortalidade, atingindo em muitos casos, uma sobrevida em longo prazo sem maiores seqüelas neurológicas, tudo isso com um manejo interdisciplinares que consiga um controle metabólico adequado...

Dieta hipoprotéica suplementada com cetoácidos em pacientes com insuficiência renal crônica / Low protein diet supplemented with ketoacids in patients with chronic renal failure

Dietas com restrição protéica são prescritas para pacientes com Insuficiência Renal Crônica (IRC) com o objetivo de aliviar a sintomatologia urêmica, retardar a progressão da IRC e melhorar as complicações metabólicas decorrentes da doença. O interesse dos efeitos potenciais da restrição protéica sobre o estado nutricional e sobre o desfecho clínico de pacientes com IRC vem crescendo. A dieta hipoprotéica suplementada com uma mistura de cetoácidos e aminoácidos essenciais parece melhorar os sintomas urêmicos, as alterações metabólicas, corrigir a proteinúria ao mesmo tempo que promove manutenção de estado nutricional adequado. Este artigo tem como objetivo fazer uma revisão de literatura sobre o efeito da dieta hipoprotéica suplementada com cetoácidos e aminoácidos essenciais nas diferentes condições clínicas e metabólicas da IRC

Utilidad de la brecha aniónica en la práctia clínica / Usefulness of anion gap in the clinical practice

En este articulo se revisa lo mas relevante acerca de la brecha aniónica. En el suero equivale a las concentraciones de Na-(Cl+HCO3), siendo el valor de referencia 12 ñ 4mmol/ L; sin embargo, recientemente, como resultado de modificaciones en la técnica para medir el cloro sérico, el valor normal para la brecha aniónica disminuyó a 10 ñ 4 mmol/L. Se resalta la importancia diagnóstica de una brecha aniónica aumentada en el paciente con acidosis metabólica, asi como el uso de la brecha aniónica en la detección de estados ácido-base mixtos. Aunque la brecha aniónica no es una variable específica, su medición resulta útil en la evaluación de desequilibrio ácido-base. La brecha aniónica es fácil de calcular y continúa siendo una herramienta diagnóstica útil, siempre que se identifiquen sus limitaciones.

Role of keto-analogues in the conservative management of chronic renal failure

One hundred patients with chronic renal failure were studied for twenty months to see the effect of a low protein diet supplemented with ketoanalogues [Ketosteril]. Their protein intake was restricted to 0.6-0.8 gms [35 kcals]/kg bw/day. Eighty two patients reported improvement and experienced enhanced physical activity, mental alertness, improved appetite and sleep. There was no generalised weakness, wasting of muscles and weight loss. Of these 82 patients, 33 showed definite improvement as their blood urea nitrogen [BUN] decreased while in 49 BUN remained stable i.e. it neither decreased nor increased. Out of the remaining 18 patients who did not show any improvement, seven are on maintenance haemodialysis, three underwent renal transplantation, five expired while three were lost to follow up. It is concluded that a low protein diet supplemented with ketoanalogues [Ketosteril] can improve uraemic symptoms, improve rehabilitation status and can thus defer an early need for dialysis

Products of non-reductive CO2 assimilation in the halophilic archaebacterium Haloferax mediterranei.

The products of CO2 fixation by heterotrophically grown Haloferax mediterranei were analysed. The main 14C-labelled alpha-ketoacid detected following incubation with NaH14CO3 and pyruvate or propionate was pyruvate. In presence of these organic acids and NH4+, 14CO2 was incorporated into glutamic and aspartic acids and alanine.

Terapia economizadora de proteínas no pós-operatório: efeitos experimentais do alfa-ceto-isocaproato / Postoperative protein sparing therapy: effects of alpha-keto-isocaproate

Os autores avaliaram experimentalmente em coelhos, os efeitos da infusäo do alfa-ceto-isocaproato na excreçäo urinária de nitrogênio no pós-operatório. A pesquisa foi realizada em três grupos de oito animais que após serem submetidos à laparotomia com manipulaçäo das alças intestinais, receberam no pós-operatório soluçäo salina, glicose a 5% e uma soluçäo contendo 1 mg/Kg de alfa-ceto-isocaproato. A quantificaçäo da perda urinária de nitrogênio pelo método Kjeldahl mostrou-se significativamente menor no grupo que recebeu o isocaproato quando comparada com os grupos salina e glicose. Com base nos dados da experimentaçäo os autores concluíram que o isocaproato apresenta um efeito de poupança de proteína refletido por uma excreçäo urinária de nitrogênio menor que quando se faz infusäo de soluçäo salina e glicose a 5% no pós-operatório

Cetoacidosis diabetica / Diabetic ketoacidosis

La cetoacidosis diabetica es una entidad que mal manejada ofrece una alta morbi-mortalidad.En este articulo de revision se presenta un analisis de los eventos fisiopatologicos que se desarrollan durante su ocurrencia, y se esboza un esquema de tratamiento que comprende el calculo de las perdidas y de los requerimientos basales de liquidos y electrolitos de acuerdo al grado de dshidratacion; reposicion de liquidos y electrolitos en las primeras ocho horas y en las restantes dieciseis horas del dia; manejo de la insulinoterapia durante la fase de hiperglicemia, cuando la glicemia es menor de 250 mg/dl, cuando se inicia la via oral y el cambio de insulina corriente a la insulina NPH. El manejo de interpretacion de los examenes de laboratorio y finalmente se hace un recuento de los errores mas frecuentes en le tratamiento de la cetoacidosis