Mohammad Mainul Islam
A novel branched-chain amino acid metabolon: Protein-protein interactions in a supramolecular complex
Islam, Mohammad Mainul; Wallin, Reidar; Wynn, R. Max; Conway, Myra; Fujii, Hisao; Mobley, James A.; Chuang, David T.; Hutson, Susan M.
Authors
Reidar Wallin
R. Max Wynn
Myra Conway Myra.Conway@uwe.ac.uk
Occasional Associate Lecturer - CHSS - DAS
Hisao Fujii
James A. Mobley
David T. Chuang
Susan M. Hutson
Abstract
The catabolic pathways of branched-chain amino acids have two common steps. The first step is deamination catalyzed by the vitamin B6-dependent branched-chain aminotransferase isozymes (BCATs) to produce branched-chain α-keto acids (BCKAs). The second step is oxidative decarboxylation of the BCKAs mediated by the branched-chain α-keto acid dehydrogenase enzyme complex (BCKD complex). The BCKD complex is organized around a cubic core consisting of 24 lipoate-bearing dihydrolipoyl transacylase (E2) subunits, associated with the branched-chain α-keto acid decarboxylase/dehydrogenase (E1), dihydrolipoamide dehydrogenase (E3), BCKD kinase, and BCKD phosphatase. In this study, we provide evidence that human mitochondrial BCAT (hBCATm) associates with the E1 decarboxylase component of the rat or human BCKD complex with a KD of 2.8 μM. NADH dissociates the complex. The E2 and E3 components do not interact with hBCATm. In the presence of hBCATm, k cat values for E1-catalyzed decarboxylation of the BCKAs are enhanced 12-fold. Mutations of hBCATm proteins in the catalytically important CXXC center or E1 proteins in the phosphorylation loop residues prevent complex formation, indicating that these regions are important for the interaction between hBCATm and E1. Our results provide evidence for substrate channeling between hBCATm and BCKD complex and formation of a metabolic unit (termed branched-chain amino acid metabolon) that can be influenced by the redox state in mitochondria. © 2007 by The American Society for Biochemistry and Molecular Biology, Inc.
| Journal Article Type | Article |
|---|---|
| Publication Date | Apr 20, 2007 |
| Journal | Journal of Biological Chemistry |
| Print ISSN | 0021-9258 |
| Electronic ISSN | 1083-351X |
| Publisher | American Society for Biochemistry and Molecular Biology |
| Peer Reviewed | Not Peer Reviewed |
| Volume | 282 |
| Issue | 16 |
| Pages | 11893-11903 |
| DOI | https://doi.org/10.1074/jbc.M700198200 |
| Public URL | https://uwe-repository.worktribe.com/output/1028428 |
| Publisher URL | http://dx.doi.org/10.1074/jbc.M700198200 |
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