Comparative metabolism and structure of BCKD-E2 in primary biliary cirrhosis
| Autor: | S. Munoz, Dean J. Danner, M. E. Gershwin, D. M. Jefferson, J. Ishida, J. M. Turchany, Takashi Iwayama, E. R. Dickson, M. Yamaguchi, Patrick S.C. Leung |
|---|---|
| Rok vydání: | 1993 |
| Předmět: |
medicine.medical_specialty
DNA Complementary Macromolecular Substances Biliary cirrhosis Immunology Cholangitis Sclerosing Molecular Sequence Data Pyruvate Dehydrogenase Complex Biology Polymerase Chain Reaction Sensitivity and Specificity 3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide) chemistry.chemical_compound Primary biliary cirrhosis Multienzyme Complexes Internal medicine medicine Immunology and Allergy Humans Amino Acid Sequence Peptide sequence Mitochondrial transport Chromatography High Pressure Liquid Binding Sites Base Sequence Liver Cirrhosis Biliary Maple syrup urine disease Ketone Oxidoreductases medicine.disease Pyruvate dehydrogenase complex Keto Acids Lipoic acid Endocrinology chemistry Liver Luminescent Measurements |
| Zdroj: | Journal of autoimmunity. 6(4) |
| ISSN: | 0896-8411 |
| Popis: | The identification and cloning of the mitochondrial autoantigens in primary biliary cirrhosis (PBC) have provided new clues in disease pathogenesis. The two major autoantigens are the E2 subunits of pyruvate dehydrogenase and branched-chain ketoacid dehydrogenase (BCKD). Interestingly, one of these complexes, BCKD-E2, is already well known to clinical medicine based on its association with genetic mutations in maple syrup urine disease (MSUD). Patients with this disease have an inability to metabolize branched-chain amino acids. In the present study, we have taken advantage of the known sequence of BCKD-E2 from normal humans, and addressed the issue of whether there is an altered autoantigen sequence in hepatocytes of individuals with primary biliary cirrhosis. In particular, we examined both the leader sequence and the B-cell immunodominant epitope, the lipoic acid domain. In addition, because patients with PBC have autoantibodies to the BCKD-E2 complex, we have quantitated plasma levels of alpha-ketoacids potentially affected in maple syrup urine disease. These include pyruvic acid (PY), phenylpyruvic acid (PP), alpha-ketoisocaproic acid (KIC) alpha-ketoisovalerate (KIV) and alpha-keto-beta-methylvaleric acid (KMV). The levels of these alpha-ketoacids were compared in patients with primary sclerosing cholangitis and normal volunteers. The sequence of BCKD-E2 obtained from PBC hepatocytes showed homology with normal BCKD. Further studies of autoantigen structure and sequence are clearly indicated, including those involved in mitochondrial transport and localization. Finally, we noted a statistically significant increase in all plasma alpha-ketoacids except alpha-keto-beta-methylvaleric acid in PBC patients.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Databáze: | OpenAIRE |
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