2-Methylbutyrylglycine
(Synonyms: N-(2-甲基-1-氧代丁基)-甘氨酸) 目录号 : GC49840
A metabolite of isoleucine
Cas No.:52320-67-9
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >95.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
2-Methylbutyrylglycine is a metabolite of the essential amino acid L-isoleucine.1,2 It is produced by hydrolysis of the L-isoleucine catabolic intermediate (S)-2-methylbutyryl-CoA, which accumulates when the activity of 2-methylbutyryl-CoA dehydrogenase is deficient. 2-Methylbutyrylglycine (0.5-5 mM) induces the formation of thiobarbituric acid reactive substances (TBARS) in isolated rat cerebral cortex.3 Elevated levels of 2-methylbutyrylglycine are associated with 2-methylbutyryl-CoA dehydrogenase deficiency (2-MBCDD), also known as short/branched-chain acyl-CoA dehydrogenase (SBCAD) deficiency.1,2
1.Gibson, K.M., Burlingame, T.G., Hogema, B., et al.2-Methylbutyryl-coenzyme A dehydrogenase deficiency: A new inborn error of L-isoleucine metabolismPediatr. Res.47(6)830-833(2000) 2.Fong, B.M.-W., Tam, S., and Leung, S.-Y.Quantification of acylglycines in human urine by HPLC electrospray ionization-tandem mass spectrometry and the establishment of pediatric reference interval in local ChineseTalanta88193-200(2012) 3.Knebel, L.A., Zanatta, Â., Tonin, A.M., et al.2-Methylbutyrylglycine induces lipid oxidative damage and decreases the antioxidant defenses in rat brainBrain Res.147874-82(2012)
| Cas No. | 52320-67-9 | SDF | Download SDF |
| 别名 | N-(2-甲基-1-氧代丁基)-甘氨酸 | ||
| Canonical SMILES | O=C(CNC(C(CC)C)=O)O | ||
| 分子式 | C7H13NO3 | 分子量 | 159.2 |
| 溶解度 | DMSO: Soluble,Ethanol: Soluble | 储存条件 | -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 6.2814 mL | 31.407 mL | 62.8141 mL |
| 5 mM | 1.2563 mL | 6.2814 mL | 12.5628 mL |
| 10 mM | 0.6281 mL | 3.1407 mL | 6.2814 mL |
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| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
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1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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2-Methylbutyrylglycine induces lipid oxidative damage and decreases the antioxidant defenses in rat brain
Brain Res 2012 Oct 10;1478:74-82.PMID:22967964DOI:10.1016/j.brainres.2012.08.039.
Short/branched chain acyl-CoA dehydrogenase (SBCAD) deficiency is an autosomal recessive disorder of isoleucine metabolism biochemically characterized by accumulation of 2-Methylbutyrylglycine (2MBG) and 2-methylbutyric acid (2MB). Affected patients present predominantly neurological symptoms, whose pathophysiology is not yet established. In the present study, we investigated the in vitro effects of 2MBG and 2MB on important parameters of oxidative stress in cerebral cortex of young rats and C6 glioma cells. 2MBG increased thiobarbituric acid-reactive species (TBA-RS), indicating an increase of lipid oxidation. 2MBG induced sulfhydryl oxidation in cortical supernatants and decreased glutathione (GSH) in these brain preparations, as well as in C6 cells, indicating a reduction of nonenzymatic brain antioxidant defenses. In contrast, 2MB did not alter any of these parameters and 2MBG and 2MB did not affect carbonyl formation (protein damage). In addition, 2MBG-induced increase of TBA-RS levels and decrease of GSH were prevented by free radical scavengers, implying that reactive species were involved in these effects. Furthermore, the decrease of GSH levels caused by 2MBG was not due to a direct oxidative action since this metabolite did not alter sulfhydryl content from a commercial solution of GSH. Nitric oxide production was not altered by 2MBG and 2MB, suggesting that reactive oxygen species possibly underlie 2MBG effects. Finally, we verified that 2MBG did not induce cell death in C6 cells. The present data show that 2MBG induces lipid oxidative damage and reduces the antioxidant defenses in rat brain. Therefore, it may be postulated that oxidative stress induced by 2MBG is involved, at least in part, in the pathophysiology of the brain damage found in SBCAD deficiency.
2-ethylhydracrylic aciduria in short/branched-chain acyl-CoA dehydrogenase deficiency: application to diagnosis and implications for the R-pathway of isoleucine oxidation
Clin Chem 2005 Mar;51(3):610-7.PMID:15615815DOI:10.1373/clinchem.2004.043265.
Background: Isolated excretion of 2-Methylbutyrylglycine (2-MBG) is the hallmark of short/branched-chain acyl-CoA dehydrogenase deficiency (SBCADD), a recently identified defect in the proximal pathway of L-isoleucine oxidation. SBCADD might be underdiagnosed because detection and recognition of urine acylglycines is problematic. Excretion of 2-ethylhydracrylic acid (2-EHA), an intermediate formed in the normally minor R-pathway of L-isoleucine oxidation, has not previously been described in SBCADD. Methods: Samples from four patients with 2-MBG excretion were analyzed by gas chromatography-mass spectrometry for urine organic acids, quantification of 2-MBG, and chiral determination of 2-methylbutyric acid. Blood-spot acylcarnitines were measured by electrospray-tandem mass spectrometry. Mutations in the ACADSB gene encoding SBCAD were identified by direct sequencing. Results: SBCADD was confirmed in each patient by demonstration of different ACADSB gene mutations. In multiple urine samples, organic acid analysis revealed a prominent 2-EHA peak usually exceeding the size of the 2-MBG peak. Approximately 40-46% of total 2-methylbutyric acid conjugates were in the form of the R-isomer, indicating significant metabolism via the R-pathway. Conclusions: If, as generally believed, SBCAD is responsible for R-2-MBG dehydrogenation in the R-pathway, 2-EHA would not be produced in SBCADD. Our observation of 2-ethylhydracrylic aciduria in SBCADD implies that a different or alternative enzyme serves this function. Increased flux through the R-pathway may act as a safety valve for overflow of accumulating S-pathway metabolites and thereby mitigate the severity of SBCADD. Awareness of 2-ethylhydracrylic aciduria as a diagnostic marker could lead to increased detection of SBCADD and improved definition of its clinical phenotype.
Clinical, biochemical, and molecular spectrum of short/branched-chain acyl-CoA dehydrogenase deficiency: two new cases and review of literature
J Pediatr Endocrinol Metab 2019 Feb 25;32(2):101-108.PMID:30730842DOI:10.1515/jpem-2018-0311.
Background Short/branched-chain acyl-CoA dehydrogenase (SBCAD) deficiency is a rare inborn error of metabolism with uncertain clinical significance. As it leads to C5-carnitine (i.e. isovalerylcarnitine, 2methylbutyrilcarnitine, or pivaloylcarnitine) elevation, SBCAD deficiency is detectable at newborn screening, requiring differential diagnosis from isovaleric acidemia and pivalic acid administration. Increased urinary excretion of 2-Methylbutyrylglycine (2MBG) is the hallmark of SBCAD deficiency. Methods We report two cases of SBCAD deficiency and provide a review of the available literature on this condition. Results Two siblings newly diagnosed with SBCAD deficiency are reported. Newborn screening allowed the early diagnosis in the second-born (C5=0.5 μmol/L, normal 0.05-0.3 μmol/L) and addressed selective screening in the 5-year asymptomatic brother (C5=1.9 μmol/L). Both patients showed increased urinary excretion of 2MBG and two mutations in the ACADSB gene (c.443C>T/c.1145C>T). Currently, both the patients are asymptomatic. Longitudinal biochemical monitoring of the two patients while on treatment with carnitine (100 mg/kg/day) was provided. Based on our experience and the literature review (162 patients), SBCAD deficiency is symptomatic in about 10% of reported patients. Clinical onset occurs in newborns or later in life with seizures, developmental delay, hypotonia, and failure to thrive. On longitudinal follow-up, epilepsy, developmental delay, microcephaly, and autism can develop. Acute metabolic decompensation due to catabolic stressors can occur, as observed in one newly reported patient. Fifteen mutations in the ACADSB gene are known, including the newly identified variant c.1145C>T (p.Thr382Met), variably associated to the phenotype. In the Hmong population, SBCAD deficiency is highly prevalent, mostly due to the founder mutation c.1165A>G, and is largely asymptomatic. Conclusions Although mostly asymptomatic, considering SBCAD deficiency as a non-disease in non-Hmong subjects appears unsafe. Catabolic situations can precipitate acute metabolic decompensation. Carnitine supplementation and valproate avoidance appear to be indicated. Providing an emergency protocol for the management of acute catabolic episodes seems reasonable in asymptomatic patients with SBCAD deficiency. Longitudinal follow-up is recommended.
2-Methylbutyryl-coenzyme A dehydrogenase deficiency: a new inborn error of L-isoleucine metabolism
Pediatr Res 2000 Jun;47(6):830-3.PMID:10832746DOI:10.1203/00006450-200006000-00025.
An 4-mo-old male was found to have an isolated increase in 2-Methylbutyrylglycine (2-MBG) and 2-methylbutyrylcamitine (2-MBC) in physiologic fluids. In vitro oxidation studies in cultured fibroblasts using 13C- and 14C-labeled branched chain amino acids indicated an isolated block in 2-methylbutyryl-CoA dehydrogenase (2-MBCDase). Western blotting revealed absence of 2-MBCDase protein in fibroblast extracts; DNA sequencing identified a single 778 C>T substitution in the 2-MBCDase coding region (778 C>T), substituting phenylalanine for leucine at amino acid 222 (L222F) and absence of enzyme activity for the 2-MBCDase protein expressed in Escherichia coli. Prenatal diagnosis in a subsequent pregnancy suggested an affected female fetus, supporting an autosomal recessive mode of inheritance. These data confirm the first documented case of isolated 2-MBCDase deficiency in humans.
Long-term monitoring for short/branched-chain acyl-CoA dehydrogenase deficiency: A single-center 4-year experience and open issues
Front Pediatr 2022 Sep 6;10:895921.PMID:36147814DOI:10.3389/fped.2022.895921.
Introduction: Short/branched-chain acyl-CoA dehydrogenase deficiency (SBCADD) is an inherited disorder of L-isoleucine metabolism due to mutations in the ACADSB gene. The role of current diagnostic biomarkers [i.e., blood 2-methylbutyrylcarnitine (C5) and urine 2-Methylbutyrylglycine (2MBG)] in patient monitoring and the effects of proposed treatments remain uncertain as follow-data are lacking. This study presents first systematic longitudinal biochemical assessment in SBCADD patients. Methods: A retrospective, observational single-center study was conducted on newborns born between 2017 and 2020 and suspected with SBCADD. Biochemical, molecular, clinical and dietary data collected upon NBS recall and during the subsequent follow-up were recorded. Results: All enrolled subjects (n = 10) received adequate protein intake and L-carnitine supplementation. Nine subjects were diagnosed with SBCADD. During the follow-up [median: 20.5 (4-40) months] no patient developed symptoms related to SBCADD. No patient normalized serum C5 and urine 2MBG values. In 7/9 SBCADD patients mean serum C5 values decreased or stabilized compared to their first serum C5 value. A major increase in serum C5 values was observed in two patients after L-carnitine discontinuation and during intercurrent illness, respectively. Urine 2MBG values showed moderate intra-patient variability. Discussion: The relatively stable serum C5 values observed during L-carnitine supplementation together with C5 increase occurring upon L-carnitine discontinuation/intercurrent illness may support the value of serum C5 as a monitoring biomarker and the benefit of this treatment in SBCADD patients. The role of urine 2MBG in patient monitoring remains uncertain. As all patients were asymptomatic, no association between biochemical parameters and clinical phenotype could be investigated in this study.