Abstract
Three patients with chronic lacticacidemia and deficiency of the pyruvate dehydrogenase complex demonstrated in cultured skin fibroblasts showed abnormalities on Western blotting with anti-pyruvate dehydrogenase complex antiserum which were not located in the E1 (alpha and beta) component of the complex. One of these patients had an enzymatically demonstrable deficiency in the E2 dihydrolipoyl transacetylase segment of the complex and very low observable E2 protein component on Western blotting of fibroblast proteins. The other two patients had abnormalities observable in the X component but no observable reduction in either E1, E2, or E3 enzymatic activities. One patient appeared to have a missing X component while the other had two distinct bands where X should be on Western blotting of fibroblast proteins. All three patients appeared to have severe clinical sequelae resulting from these defects. This is the first time that defects in either the E2 or the X component of the pyruvate dehydrogenase complex have been observed in the human population.
Full text
PDF
Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Brada D., Roth J. "Golden blot"--detection of polyclonal and monoclonal antibodies bound to antigens on nitrocellulose by protein A-gold complexes. Anal Biochem. 1984 Oct;142(1):79–83. doi: 10.1016/0003-2697(84)90518-9. [DOI] [PubMed] [Google Scholar]
- Butterworth P. J., Tsai C. S., Eley M. H., Roche T. E., Reed L. J. A kinetic study of dihydrolipoyl transacetylase from bovine kidney. J Biol Chem. 1975 Mar 10;250(5):1921–1925. [PubMed] [Google Scholar]
- De Marcucci O. G., Hodgson J. A., Lindsay J. G. The Mr-50 000 polypeptide of mammalian pyruvate dehydrogenase complex participates in the acetylation reactions. Eur J Biochem. 1986 Aug 1;158(3):587–594. doi: 10.1111/j.1432-1033.1986.tb09795.x. [DOI] [PubMed] [Google Scholar]
- Hodgson J. A., De Marcucci O. G., Lindsay J. G. Lipoic acid is the site of substrate-dependent acetylation of component X in ox heart pyruvate dehydrogenase multienzyme complex. Eur J Biochem. 1986 Aug 1;158(3):595–600. doi: 10.1111/j.1432-1033.1986.tb09796.x. [DOI] [PubMed] [Google Scholar]
- Jilka J. M., Rahmatullah M., Kazemi M., Roche T. E. Properties of a newly characterized protein of the bovine kidney pyruvate dehydrogenase complex. J Biol Chem. 1986 Feb 5;261(4):1858–1867. [PubMed] [Google Scholar]
- Matuda S., Nakano K., Tabata I., Matuo S., Saheki T. Properties of component X of rat heart pyruvate dehydrogenase complex. Biochem Biophys Res Commun. 1988 Jan 29;150(2):816–821. doi: 10.1016/0006-291x(88)90464-0. [DOI] [PubMed] [Google Scholar]
- Rahmatullah M., Roche T. E. The catalytic requirements for reduction and acetylation of protein X and the related regulation of various forms of resolved pyruvate dehydrogenase kinase. J Biol Chem. 1987 Jul 25;262(21):10265–10271. [PubMed] [Google Scholar]
- Robinson B. H., Chun K., Mackay N., Otulakowski G., Petrova-Benedict R., Willard H. Isolated and combined deficiencies of the alpha-keto acid dehydrogenase complexes. Ann N Y Acad Sci. 1989;573:337–346. doi: 10.1111/j.1749-6632.1989.tb15009.x. [DOI] [PubMed] [Google Scholar]
- Robinson B. H., MacMillan H., Petrova-Benedict R., Sherwood W. G. Variable clinical presentation in patients with defective E1 component of pyruvate dehydrogenase complex. J Pediatr. 1987 Oct;111(4):525–533. doi: 10.1016/s0022-3476(87)80112-9. [DOI] [PubMed] [Google Scholar]
- Robinson B. H., Taylor J., Sherwood W. G. The genetic heterogeneity of lactic acidosis: occurrence of recognizable inborn errors of metabolism in pediatric population with lactic acidosis. Pediatr Res. 1980 Aug;14(8):956–962. doi: 10.1203/00006450-198008000-00013. [DOI] [PubMed] [Google Scholar]
- Sheu K. F., Hu C. W., Utter M. F. Pyruvate dehydrogenase complex activity in normal and deficient fibroblasts. J Clin Invest. 1981 May;67(5):1463–1471. doi: 10.1172/JCI110176. [DOI] [PMC free article] [PubMed] [Google Scholar]