Pyruvate dehydrogenase deficiencies

  • J. P. Blass

Abstract

The extraordinary complexity of the pyruvate dehydrogenase complex (PDHC) is clearly documented in Chapter 12. PDHC contains three catalytic and two regulatory enzymes. It is subject to an intricate array of controls, including phosphorylation and dephosphorylation of the α-subunit of its thiamin-dependent component, end-product inhibition by NADH and acetyl-coenzyme A, and the action of a number of effectors. Furthermore, there is relatively little excess of this enzyme compared to the normal flux of its substrate, both in brain1 and in other tissues2. The control of PDHC in health and disease is a subject of intense research in a number of laboratories at the present time, particularly in relation to diabetes and the mechanism of action of insulin. Even subtle changes in the structure of one of the proteins in PDHC could lead to metabolically significant impairment of its activity. Conversely, one can conceive of a wide variety of metabolic alterations which could lead to secondary impairment of the activity of PDHC and present clinically as deficiencies of PDHC. In view of this complexity, it is not surprising that the deficiencies of PDHC which have been described have not yet been fully characterized in biochemical detail.

Keywords

Choline Acetylcholine Myopathy Dystonia Syphilis 

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© The Society for the Study of Inborn Errors of Metabolism 1980

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  • J. P. Blass

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