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IDENTIFICATION AND CHARACTERIZATION OF BRANCHED‐CHAIN AMINO ACID (BCAA) METABOLON PROTEINS: ROLE OF GLUTAMATE DEHYDROGENASE
Author(s) -
Islam Mohammad Mainul,
Nautiyal Manisha,
Mobley James,
Hutson Susan
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.610.4
Subject(s) - chemistry , oxidative deamination , biochemistry , deamination , transamination , glutamate dehydrogenase , allosteric regulation , decarboxylation , dehydrogenase , amino acid , valine , enzyme , glutamate receptor , catalysis , receptor
The catabolic pathway for branched‐chain amino acids (BCAAs) include deamination followed by oxidative decarboxylation of the deaminated product branched‐chain α‐keto acids (BCKAs), catalyzed by mitochondrial branched‐chain aminotransferase (BCATm) and branched‐chain α‐keto acid dehydrogenase enzyme complex (BCKDC), respectively. We have found that BCATm binds to the E1 decarboxylase of BCKDC, forming a metabolon that allows channeling of BCKAs from BCATm to E1. The metabolon also contains glutamate dehydrogenase (GDH1). We show that GDH1 only binds to the pyridoxamine 5’‐phosphate (PMP)‐form of BCATm (PMP‐BCATm), and does not bind to pyridoxal 5’‐phosphate‐BCATm (PLP‐BCATm) or BCKDC components. Leucine allosterically activates GDH1 and oxidative deamination of glutamate is increased further by addition of PLP‐BCATm. Isoleucine and valine are not allosteric activators; but in the presence of PLP‐hBCATm, convert it to PMP‐BCATm, stimulating GDH1 activity. Kinetic results suggest that α‐ketoglutarate (α‐KG) produced by GDH1‐catalyzed oxidative deamination of glutamate is channeled directly to BCATm. Then BCATm is converted to PLP‐BCATm transferring BCAA nitrogen to α‐KG. Thus GDH1 facilitates regeneration of the form of BCATm that binds to the E1 decarboxylase of the BCKDC, and promotes metabolon formation, BCAA oxidation and nitrogen transfer to glutamate. (NIH DK34738).