2-Oxo acid dehydrogenase complexes of multicellular organisms
Article first published online: 3 MAR 2003
European Journal of Biochemistry
Volume 270, Issue 6, page 1035, March 2003
How to Cite
Bunik, V. I. (2003), 2-Oxo acid dehydrogenase complexes of multicellular organisms. European Journal of Biochemistry, 270: 1035. doi: 10.1046/j.1432-1033.2003.03467.x
- Issue published online: 3 MAR 2003
- Article first published online: 3 MAR 2003
Investigation of the 2-oxo acid dehydrogenase multienzyme complexes (Mr ≈ 106−107 Da) has many facets, from studies of organic catalysis within the protein structure to unraveling general principles of multienzyme complex assembly [1–5]. It bridges bioorganic chemistry and cell biology, and is both fascinating in itself and important methodologically. In particular, 2-oxo acid dehydrogenase complexes are inexhaustible source of valuable data for understanding the biological significance of protein assemblies. A new type of symmetry-driven dynamics of the complexes has also been suggested : the ‘breathing’ of the macromolecular structure is presumed to have an impact on its catalysis and regulation, although the exact relationship between the dynamics and function is still to be established. Studies of the transfer of intermediates within the complexes have revealed a multiple random coupling mechanism provided by a network of covalently attached lipoyl groups in the complex multimeric core, with catalysis accelerated in part by mechanical movements of domains .
In this Minireview series, we demonstrate the benefits of multienzyme assemblies for integrated functional regulation. Thus, only one molecule of the pyruvate dehydrogenase kinase may be employed by the 60-meric core to rapidly inactivate all molecules of the first component enzyme in a process sensitive to the chemical state of the lipoyl groups in the assembly (Minireview in this series, Roche et al.). Another advantage of an extended complex is its ability to create compartments of biologically active intermediates. This not only increases the local concentration of the intermediate, but also influences its reactivity, enabling reactions that are not efficient with the same number of separate molecules (Minireviews in this series, Bunik and Roche et al.).
What allows the enzyme complexes to satisfy the additional requirements of multicellular organisms? We address this question by focusing on the regulation of the 2-oxo acid dehydrogenase complexes from higher plants and animals. The first Minireview presents data on specific intra-organellar regulation of mammalian complexes by mitochondrial thioredoxin. Such regulation appears to have evolved along with protein compartmentalization within the mitochondria. The second Minireview considers peculiarities of the 2-oxo acid dehydrogenase complexes within the different cellular compartments, mitochondria and chloroplasts. Specific metabolic requirements of the organelles are met through modified regulation of the same catalytic process. This principle is also applied at the tissue level. Study of the pyruvate dehydrogenase regulation by phosphorylation (third Minireview) demonstrates that the enzyme function is adjusted to metabolic demands of different tissues by the tissue-specific kinases and phosphatases. Thus, multicellular systems are characterized by an increased complexity of the enzyme regulation; organization of proteins into multienzyme structures is a powerful means to extend the opportunities for regulation.
Victoria Bunik is currently a senior scientist of the A.N. Belozersky Institute of Physico-Chemical Biology, Moscow M.V. Lomonosov State University looking at the structure–function relationship in the 2-oxo acid dehydrogenase complexes following her PhD (1987) and Doctor of Chemical Sciences (2001) in the same field. In 1992 she was awarded the Moscow M.V. Lomonosov State University award for the best research among young scientists. Victoria has collaborated with several laboratories in Europe and the USA, including a period (1996–1997) of research at Tuebingen University in Germany provided for by a fellowship from the Alexander von Humboldt Foundation (Bonn, Germany), which she received in 1995.