Pyruvate dehydrogenase structure

Packman, L.C., and Perham, R.N. (1982) Quaternary structure of the pyruvate dehydrogenase multienzyme complex of Bacillus stearothermophilus studied by a new reversible cross-linking procedure with bis(imidoesters). Biochemistry 21, 5171-5175. 

Figure 3.4 Structure of two prosthetic groups (a) biotin (b) lipoate. Biotin functions as a carboxyl group carrier, e.g. in acetyl-CoA carboxylase. Lipoate is presented in its oxidised form (-S-S-). It is a cofactor for pyruvate dehydrogenase and oxoglu-tarate dehydrogenase.

Figure 6.5 Details of the glycolytic pathway. All the enzymes except pyruvate dehydrogenase are present in the cytosol. The pathway, presently the molecular structured of the intermediates, is described in Appendix 6.3.

A. Structure of thiamine and its cofactor form, thiamine pyrophosphate. B. Structure of intermediate formed in the reaction catalyzed by pyruvate dehydrogenase. C. Structure of intermediate formed in the reaction catalyzed by a-keto-glutarate dehydrogenase. 

Electron microscopy of the core dihydrolipoyl transacylase from E. coli reveals a striking octahedral symmetry which has been confirmed by X-ray diffraction.306 3073 The core from pyruvate dehydrogenase has a mass of 2390 kDa and contains 24 identical 99.5-kDa E2 subunits. The 2-oxoglutarate dehydrogenase from E. coli has a similar but slightly less symmetric structure. Each core subunit is composed of three domains. A lipoyl group is bound in amide linkage to lysine 42 and protrudes from one end of the domain. 

Describe the subunit structure of the enzyme pyruvate dehydrogenase. Discuss the functioning of each of the coenzymes that are associated with these subunits and write detailed mechanisms for each step in the pyruvate dehydrogenase reaction. 

Mitochondrial pyruvate dehydrogenase, which contains a 60-subunit icosohedral core of dihydrolipoyl-transacylase (Fig. 15-14), is associated with three molecules of a two-subunit kinase as well as six molecules of a structural binding protein which contains a... 

Zhou ZH, McCarthy DB, O Connor CM, et al. The remarkable structural and functional organization of the eukaryotic pyruvate dehydrogenase complexes.Proc Natl Acad Sci USA 98 14802-14807, 2001. 

FIGURE 50.7. Lewisite, its structure and mechanism of action. Lewisite forms covalent bonds with lipoic acid, inactivating the en2yme pyruvate dehydrogenase (PDH). 

Although the structure of an intact member of the pyruvate dehydrogenase complex family has not yet been determined in atomic detail, the structures of all of the component enzymes are now known, albeit from different complexes and species. Thus, it is now possible to construct an atomic model of the complex to understand its activity (Figure 17.7). 

Vitamins are required in the diet for groMh, maintenance, and reproduction. These qualities are shared by other nutrients, such as the amino adds and the minerals- Why are amino acids and minerals not called vitamins The vitamins share a family of characteristics. They are organic compounds required in the diet in only smaii amounts They are not catabolized to satisfy part of the energy requirement and are not used for structural purposes. Many vitamins are used as cofactors for enzymes. Pyruvate dehydrogenase is one striking example. This enzj me uses five cofactors, where four of these cofactors are derived from vitamins-... 

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