Ca2+-dependent inhibition of branched-chain α-ketoacid dehydrogenase kinase by thiamine pyrophosphate. 2018

Seisuke Noguchi, and Yusuke Kondo, and Rina Ito, and Takahiro Katayama, and Shunsuke Kazama, and Yoshihiro Kadota, and Yasuyuki Kitaura, and Robert A Harris, and Yoshiharu Shimomura
Laboratory of Nutritional Biochemistry, Department of Applied Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, 464-8601, Japan.

Catabolism of the branched-chain amino acids (BCAAs: leucine, isoleucine, and valine) is regulated by the branched-chain α-ketoacid dehydrogenase (BCKDH) complex, which in turn is regulated by phosphorylation catalyzed by BCKDH kinase (BDK). Thiamine pyrophosphate (TPP) is required as a coenzyme for the E1 component of the BCKDH complex and can also bring about activation of the complex by inhibiting BDK. The present study shows that free Ca2+ in the physiological range greatly increases the sensitivity of BDK to inhibition by TPP (IC50 of 2.5 μM in the presence of 1 μM free Ca2+). This novel mechanism may be responsible for the stimulation of BCAA oxidation by conditions that increase mitochondrial free Ca2+ levels, e.g. in skeletal muscle during exercise.

UI MeSH Term Description Entries
D008297 Male Males
D008931 Mitochondria, Muscle Mitochondria of skeletal and smooth muscle. It does not include myocardial mitochondria for which MITOCHONDRIA, HEART is available. Sarcosomes,Mitochondrion, Muscle,Muscle Mitochondria,Muscle Mitochondrion,Sarcosome
D010766 Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Phosphorylations
D011494 Protein Kinases A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein. Protein Kinase,Kinase, Protein,Kinases, Protein
D002118 Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012694 Serine A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from GLYCINE or THREONINE. It is involved in the biosynthesis of PURINES; PYRIMIDINES; and other amino acids. L-Serine,L Serine
D013835 Thiamine Pyrophosphate The coenzyme form of Vitamin B1 present in many animal tissues. It is a required intermediate in the PYRUVATE DEHYDROGENASE COMPLEX and the KETOGLUTARATE DEHYDROGENASE COMPLEX. Cocarboxylase,Thiamine Diphosphate,Berolase,Pyrophosphate, Thiamine
D017207 Rats, Sprague-Dawley A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company. Holtzman Rat,Rats, Holtzman,Sprague-Dawley Rat,Rats, Sprague Dawley,Holtzman Rats,Rat, Holtzman,Rat, Sprague-Dawley,Sprague Dawley Rat,Sprague Dawley Rats,Sprague-Dawley Rats
D042942 3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide) A ketone oxidoreductase that catalyzes the overall conversion of alpha-keto acids to ACYL-CoA and CO2. The enzyme requires THIAMINE DIPHOSPHATE as a cofactor. Defects in genes that code for subunits of the enzyme are a cause of MAPLE SYRUP URINE DISEASE. The enzyme was formerly classified as EC 1.2.4.3. 2-Oxoisovalerate Dehydrogenase (Lipoamide),2-Oxoisocaproate Dehydrogenase,Alpha-Keto Acid Dehydrogenase,BCKA Decarboxylase,Branched Chain Alpha-Keto Acid Decarboxylase,Branched Chain Ketoacid Dehydrogenase,Branched-Chain 2-Oxo Acid Dehydrogenase,Branched-Chain Keto Acid Dehydrogenase,Branched-Chain Oxo-Acid Dehydrogenase,2 Oxoisocaproate Dehydrogenase,Acid Dehydrogenase, Alpha-Keto,Alpha Keto Acid Dehydrogenase,Branched Chain 2 Oxo Acid Dehydrogenase,Branched Chain Alpha Keto Acid Decarboxylase,Branched Chain Keto Acid Dehydrogenase,Branched Chain Oxo Acid Dehydrogenase,Decarboxylase, BCKA,Dehydrogenase, 2-Oxoisocaproate,Dehydrogenase, Alpha-Keto Acid,Dehydrogenase, Branched-Chain Oxo-Acid,Oxo-Acid Dehydrogenase, Branched-Chain

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