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.

Clinical observation of glucocorticoid combined with compoundα-keto acids therapy in primary nephrotic syndrome / 实用医学杂志

Objective To investigate the therapeutic effect and safety of glucocorticoid combined with compoundα-keto acids therapy in primary nephrotic syndrome. Methods A prospective randomized controlled trial was carried out.Seventy-two cases of primary nephrotic syndrome were equally divided into treatment group and control group. Two groups of patients were both treated with glucocorticoids , and combined with compoundα-keto acid tablets in the treatment group. The level of BUN ,Scr,CRP,IL-6,PA、Alb,TG,TC,Ca in blood and eGFR、MTP were detected before treatment and the 2nd,4th,6th,8th month after treatment to evaluate the efficacy and safety respectively. Results After 8 months of treatment, the total effective rate in treatment group was significantly higher than that in the control group (P 0.05); the level of MTP,TC,TG,CRP、IL-6 in the treatment group were significantly lower and the Alb level in the treatment group was significantly higher (P 0.05) between two groups;All of patients with no serious adverse reactions occurred during the investigation. Conclusion The curative effect of glucocorticoid combined with compoundα-keto acids therapy in primary nephrotic syndrome is sure and without significant sideeffect.

Efficacy and safety of low-protein diet combined with α-keto acids on chronic hepatitis B patients complicated with chronic kidney diseases / 中华肾脏病杂志

Objective To evaluate the efficacy and safety of short-term restriction of dietary protein intake (DPI) supplemented with α-keto acids on chronic hepatitis B patients complicated with chronic kidney diseases (CKD). Methods A prospective randomized controlled trial was carried out.Seventeen chronic hepatitis B patients with CKD were randomized to either low DPI with α-keto acid-supplemented (sLP) or low DPI (LP) group for 3 months.Low-protein diet (LPD) was individualized with total energy intake 125.52-146.44 kJ·kg-1 ·d-1,and protein intake of 0.6-0.8 g·kg-1·d-1.α-keto acid was supplied in a dosage of 0.1 g·kg-1·d-1.Nutritional indexes were recorded and other clinical indexes were measured to evaluate the efficacy and safety respectively. Results The urine protein excretion level and microalbuminuria were significantly decreased at the end of the observation period in the sLP group compared to the basal value and the LP group [24 h urine protein:baseline (4.52±1.74) g,the 1st month (3.19±1.52) g,the 2nd month (2.19±1.1) g,the 3rd month (1.64±0.77) g,P＜0.05; microalbuminyria:baseline (2855.43±248.03) mg/L,the 1st month (2157.14±218.15) mg/L,the 2nd month (1681.57±146.18) mg/L,the 3rd month (924.29±83.33) mg/L,P＜0.05].No significant difference was found in Scr and eGFR.Nutritional indexes (SGA,serume albumin) were significantly higher at the end of 3 months in the sLP group (P＜0.05).No obvious side-effect occurred. Conclusions Short-term restriction of DPI is safe,and when combined with α-keto acids,can increase serum protein and decrease urine protein excretion in chronic hepatitis B patients complicated with CKD without significant sideeffect.

Effects of low protein diet with α-keto acid supplement on kidney sclerosis and renin-angiotensin system in renal ablation rats / 中华肾脏病杂志

Objective To observe the influence of low protein diet with α-keto acid on kidney sclerosis and renin-angiotensin system in renal ablation rats. Methods Chronic renal failure rat model was established by renal ablation in 30 male SD rats,then the animals were randomly assigned to the following diet groups:normal protein group (NPD:18%casein protein),low protein group (LPD:6%casein protein) and supplemented low protein group (LK:5%casein protein+1%α-keto acids).Ten male SD sham-operated rats received 18%casein protein as control.All the rats were killed at the end of the 12th week.Pathologic changes were assessed by PAS staining.Ang II in homogenate and plasma were measured by radioimmunoassay and ELISA respectively.Immunohistochemistry and Western blotting were used to detect the protein expression of TGF-β1,renin and AT1R.Real-time PCR was used to detect the gene expression of renin and ATla,the main subtype of AT1 receptor. Results Body weight,total protein and serum albumin had not significant difference among the four groups(all P>0.05).Serum creatinine and proteinuria of nephrectomized rats were significantly higher compared to the control group (all P<0.05).Proteinuria of the LK group was lower than that of NPD and LPD groups (all P<0.05).Pathological results indicated fibrosis indices were significantly improved after LPD and LK intervention.Expressions of renin,Ang II and AT1R in LK group were significantly lower than those in NPD group (all P<0.05). Conclusions Low protein diet with α-keto acids supplement therapy exhibits renal protective effects of reducing urine protein excretion and improving renal fibrosis,which might be related to the attenuation of local renin-angiotensin system in activity nephrectomized rats.

Change of renin-angiotensin system in cultured mesangial cells by serum from nephrectomized rats feeding with low protein diet and α-keto acid supplement / 中华肾脏病杂志

Objective To observe the changes of renin-angiotensin system (RAS) in cultured mesangial cells by serum from 3/4 nephrectomized rats feeding with low protein diet and α-keto acid. Methods Thirty male SD rats received 3/4 nephrectomy (Nx) were placed on 18%normal protein diet (NPD,n=10),6% low protein diet(LPD,n=10) or 5% low protein plus 1%α-keto acid diet (LK,n=10) flor 12 weeks.Ten male SD sham-operated rats fed with 18% normal protein diet were used as control (sham group).In addition,mesangial cells were cultured in sera (10%) collected from above animals treated with or without losartan (0.02 mmol/L)for 48 hours.ELISA was applied to detect the level of Ang II,TGF-β1 and fibronectin (FN) in cell medium.Westem blotting was used to determine the protein level of ATI receptor (AT1R)and real-time PCR was used to detect the mRNA level of AT1R,TGF-β1 and FN. Results (1) Nutritional indices including body weight,total protein and albumin had no significant difference in each group. (2) Serum creatinine and 24 h pruteinuria were significantly inceased in nephrectomized groups compared to sham group(P<0.05,respectively).24 h proteinuria was greatly lower in LK group than that in NPD and LPD groups(P<0.05,respectively).(3)LK greatly decteased the level of Ang II[NPD(12.70±0.12)mg/g protein;sham(8.04±0.62)mg/g protein]in supernatant as well as the protein and mRNA expression of AT1R in cultured mesangial cells (P<0.05).(4)NPD serum directly induced higher secretion[FN:sham(20.58±0.46)g/g protein,NPD (39.84±0.06)g/g protein;TGF-β1:sham(10.12±O.56)mg/g protein,NPD(83.85±3.58)mg/g protein] and mRNA expression of FN and TGF-β1 compared with sham group (P<0.05).LPD decreased these increment (P<0.05) and LK showed stronger inhibitory effect (P<0.05). (5)Losartan application sharply reduced FN and TGF-β1 production both in supematant and in mRNA expression in NPD serum treated cells (P<0.05,respectively). Conclusion Low protein diet with α-keto acids supplement directly inhibits the RAS in mesangial cells which may contribute to its beneficial effect on the kidney.

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.

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...