scholarly journals The Impact of the Branched-Chain Ketoacid Dehydrogenase Complex on Amino Acid Homeostasis in Arabidopsis

2015 ◽  
pp. pp.00461.2015 ◽  
Author(s):  
Cheng Peng ◽  
Sahra Uygun ◽  
Shin-Han Shiu ◽  
Robert, L. Last
Keyword(s):  
Amino Acid ◽  
Amino Acid Homeostasis ◽  
Branched Chain ◽  
Ketoacid Dehydrogenase ◽  
The Impact ◽  
Dehydrogenase Complex

scholarly journals Branched-chain amino acid metabolism is regulated by ERRα in primary human myotubes and is further impaired by glucose loading in type 2 diabetes

Diabetologia ◽  
2021 ◽  
Author(s):  
Rasmus J. O. Sjögren ◽  
David Rizo-Roca ◽  
Alexander V. Chibalin ◽  
Elin Chorell ◽  
Regula Furrer ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Amino Acid ◽  
Glucose Homeostasis ◽  
Gene Set ◽  
Branched Chain Amino Acid ◽  
Human Myotubes ◽  
Branched Chain ◽  
The Impact

Abstract Aims/hypothesis Increased levels of branched-chain amino acids (BCAAs) are associated with type 2 diabetes pathogenesis. However, most metabolomic studies are limited to an analysis of plasma metabolites under fasting conditions, rather than the dynamic shift in response to a metabolic challenge. Moreover, metabolomic profiles of peripheral tissues involved in glucose homeostasis are scarce and the transcriptomic regulation of genes involved in BCAA catabolism is partially unknown. This study aimed to identify differences in circulating and skeletal muscle BCAA levels in response to an OGTT in individuals with normal glucose tolerance (NGT) or type 2 diabetes. Additionally, transcription factors involved in the regulation of the BCAA gene set were identified. Methods Plasma and vastus lateralis muscle biopsies were obtained from individuals with NGT or type 2 diabetes before and after an OGTT. Plasma and quadriceps muscles were harvested from skeletal muscle-specific Ppargc1a knockout and transgenic mice. BCAA-related metabolites and genes were assessed by LC-MS/MS and quantitative RT-PCR, respectively. Small interfering RNA and adenovirus-mediated overexpression techniques were used in primary human skeletal muscle cells to study the role of PPARGC1A and ESRRA in the expression of the BCAA gene set. Radiolabelled leucine was used to analyse the impact of oestrogen-related receptor α (ERRα) knockdown on leucine oxidation. Results Impairments in BCAA catabolism in people with type 2 diabetes under fasting conditions were exacerbated after a glucose load. Branched-chain keto acids were reduced 37–56% after an OGTT in the NGT group, whereas no changes were detected in individuals with type 2 diabetes. These changes were concomitant with a stronger correlation with glucose homeostasis biomarkers and downregulated expression of branched-chain amino acid transaminase 2, branched-chain keto acid dehydrogenase complex subunits and 69% of downstream BCAA-related genes in skeletal muscle. In primary human myotubes overexpressing peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α, encoded by PPARGC1A), 61% of the analysed BCAA genes were upregulated, while 67% were downregulated in the quadriceps of skeletal muscle-specific Ppargc1a knockout mice. ESRRA (encoding ERRα) silencing completely abrogated the PGC-1α-induced upregulation of BCAA-related genes in primary human myotubes. Conclusions/interpretation Metabolic inflexibility in type 2 diabetes impacts BCAA homeostasis and attenuates the decrease in circulating and skeletal muscle BCAA-related metabolites after a glucose challenge. Transcriptional regulation of BCAA genes in primary human myotubes via PGC-1α is ERRα-dependent. Graphical abstract

Effect of Dietary Protein on the Liver Content and Subunit Composition of the Branched-Chain α-Ketoacid Dehydrogenase Complex

1994 ◽  
Vol 308 (2) ◽  
pp. 446-453 ◽  
Author(s):  
Y. Zhao ◽  
K.M. Popov ◽  
Y. Shimomura ◽  
N.Y. Kedishvili ◽  
J. Jaskiewicz ◽  
...  
Keyword(s):  
Dietary Protein ◽  
Subunit Composition ◽  
Branched Chain ◽  
Ketoacid Dehydrogenase ◽  
Dehydrogenase Complex

Adverse effect of fenofibrate on branched-chain α-ketoacid dehydrogenase complex in rat's liver

Toxicology ◽  
2009 ◽  
Vol 266 (1-3) ◽  
pp. 1-5 ◽  
Author(s):  
Malgorzata Knapik-Czajka ◽  
Anna Gozdzialska ◽  
Jerzy Jaskiewicz
Keyword(s):  
Adverse Effect ◽  
Branched Chain ◽  
Ketoacid Dehydrogenase ◽  
Dehydrogenase Complex

Purification of branched chain α-ketoacid dehydrogenase complex from rat liver

1987 ◽  
Vol 163 (1) ◽  
pp. 74-78 ◽  
Author(s):  
Yoshiharu Shimomura ◽  
Ralph Paxton ◽  
Takayuki Ozawa ◽  
Robert A. Harris
Keyword(s):  
Rat Liver ◽  
Branched Chain ◽  
Ketoacid Dehydrogenase ◽  
Dehydrogenase Complex
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