Primary Biliary Cirrhosis Serum Inhibits Activity of Pyruvate, Oxoglutarate and Branched Chain Oxo Acid Dehydrogenase

1990 ◽  
Vol 78 (s22) ◽  
pp. 1P-1P
Author(s):  
JP Begley ◽  
R Barry ◽  
RM Denton ◽  
D Stansbie
Keyword(s):  
Primary Biliary Cirrhosis ◽  
Biliary Cirrhosis ◽  
Acid Dehydrogenase ◽  
Branched Chain

scholarly journals Characterization of Autoantibodies against the E1 Subunit of Branched-Chain 2-Oxoacid Dehydrogenase in Patients with Primary Biliary Cirrhosis

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Tsutomu Mori ◽  
Hiromasa Ohira ◽  
Masahito Kuroda ◽  
Masaki Kato ◽  
Yoshiki Yamaguchi ◽  
...  
Keyword(s):  
Enzyme Activity ◽  
Primary Biliary Cirrhosis ◽  
Active Center ◽  
Epitope Mapping ◽  
Biliary Cirrhosis ◽  
Antimitochondrial Antibodies ◽  
Points Of View ◽  
Branched Chain

Primary biliary cirrhosis (PBC) is characterized by antimitochondrial antibodies (AMAs) that react with the lipoyl-containing E2 subunits of 2-oxoacid dehydrogenase complexes such as BCOADC and PDC. The lipoyl domains of E2 contain the major epitopes essential for immunopathology. However, the non-lipoyl-containing E1 subunits are also frequently targeted. Since anti-E1 antibodies always appear in combination with anti-E2 antibodies, the mechanisms underlying the autoimmunity against E1 may be linked to, but distinct from, those against E2. Here, we demonstrate that intermolecular and intramolecular determinant spreading underlies the autoimmunity against E1. We performed characterizations and epitope mapping for anti-BCOADC-E1 antibodies from both the intermolecular and intramolecular points of view. The antibody reactivities form a cluster against the BCOADC complex that is distinct from that against the PDC complex, and the anti-BCOADC-E1 antibodies arise as part of the cluster against the BCOADC complex. Multiple epitopes are present on the surface of the BCOADC-E1 molecule, and the major epitope overlaps with the active center. Sera with anti-BCOADC-E1 antibodies strongly inhibited the enzyme activity. These findings suggest that the E1 subunit as part of the native BCOADC complex is an immunogen, and that determinant spreading is involved in the pathogenesis of AMA production.

Regulation of the ?-Keto Acid Dehydrogenase Complexes and Their Involvement in Primary Biliary Cirrhosis

1989 ◽  
Vol 573 (1 Alpha-Keto Ac) ◽  
pp. 183-191
Author(s):  
S. J. YEAMAN ◽  
M. F. BASSENDINE ◽  
D. FITTES ◽  
D. R. HODGSON ◽  
L. HESELTINE ◽  
...  
Keyword(s):  
Primary Biliary Cirrhosis ◽  
Biliary Cirrhosis ◽  
Keto Acid ◽  
Acid Dehydrogenase
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