The methods described here represent a flexible set of procedures for investigating the metabolism of the branched-chain alpha-keto acids and other substances in perfused organs, notably the rat heart and liver. These procedures have been used to investigate many aspects of the metabolism of the branched-chain alpha-keto acids not discussed here, such as the effects on branched-chain alpha-keto acid metabolism by exposure to alpha-adrenergic agents, by inhibition of the monocarboxylate translocator, and by the coinfusion of other metabolites.
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http://dx.doi.org/10.1016/s0076-6879(88)66062-9 | DOI Listing |
JIMD Rep
January 2025
Division of Genetics and Genomic Medicine, Department of Pediatrics Washington University School of Medicine St. Louis Missouri USA.
Maple syrup urine disease (MSUD) is an inborn error of metabolism characterized by the accumulation of branched-chain amino acids (leucine, isoleucine, and valine) caused by a defect in the branched-chain alpha-keto acid dehydrogenase complex. Liver transplant is an effective therapy for MSUD, and patients can usually tolerate a regular diet after transplant without symptomatic metabolic decompensation. Most post-transplant patients do not follow a sick-day diet.
View Article and Find Full Text PDFBiochem Biophys Res Commun
January 2025
Department of Biochemistry and Molecular Biology, Graduate School of Medical Science, Yamagata University, Japan.
Branched-chain amino acids (BCAAs) facilitate cancer cell proliferation and survival. Stresses, including X-irradiation, increase BCAA uptake. However, the role of BCAA metabolism in cancer cell survival remains unclear.
View Article and Find Full Text PDFACS Med Chem Lett
November 2024
Department of Biochemistry, UT Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, Texas 75390-9038, United States.
Elevated levels of the branched chain α-amino acids valine, leucine, and isoleucine are associated with heart disease and metabolic disorders. The kinase BDK, also known as branched-chain ketoacid dehydrogenase kinase (BCKDK), is a negative regulator of branched-chain α-amino acid metabolism through deactivation of BCKDC, the branched-chain α-ketoacid dehydrogenase complex. Inhibitors of BDK increase the activity of BCKDC and could be useful therapeutic leads for cardiometabolic diseases.
View Article and Find Full Text PDFMol Biol Rep
November 2024
Department of Gastroenterology and Hepatology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands.
Background: End-stage liver diseases (ESLDs) are a significant global health challenge due to their high prevalence and severe health impacts. Despite the severe outcomes associated with ESLDs, therapeutic options remain limited. Targeting the activation of hepatic stellate cells (HSCs), key drivers of extracellular matrix accumulation during liver injury presents a novel therapeutic approach.
View Article and Find Full Text PDFOrphanet J Rare Dis
October 2024
Division of Medical Genetics, Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
Background: Maple syrup urine disease (MSUD) is a rare autosomal recessive metabolic disorder caused by variants in any of the following genes: BCKDHA, BCKDHB, and DBT gene. Previous reports have highlighted a variety of common causing genes and variants among different ethnic groups affected by MSUD. This study is the first to describe the molecular characteristics, potential common variants, clinical phenotypes, and treatment outcomes of 20 Thai MSUD patients before the implementation of expanded newborn screening in Thailand.
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