Moonlighting Function of the Tubulin Cytoskeleton: Macromolecular Architectures in the Cytoplasm - Systems Biology of Metabolic and Signaling Networks - page 170

Fig. 7.6 Energy metabolism in HD (n171-82q) transgenic mouse. Activation of hexokinase,
enolase, and pyruvate kinase ( PK ); inhibition of GAPDH; increased glycolytic flux; no alteration
in mitochondrial complexes
suggest that it may not be a metabolic disease but, rather, a conformational one. In
fact, various genetic mutations that alter this enzyme have been identified; these
mutations result in decrease in the catalytic activity and likely in its oligomerization
state. However, the mutations do not affect energy metabolism but result in
accumulation of dihydroxyacetone phosphate followed by its chemical conversion
into the toxic methylglyoxal. This results in the formation of advanced glycation
end products and aberrant protein-protein interactions. Such interactions result in
proteins sticking to microtubules and in the formation of aggregation-prone
proteins, a typical trait of molecular conformational disorders.
7.5 Concluding Remark
In the cytoskeletal sensor hypothesis it has been proposed recently that the cyto-
skeleton senses and integrates the general metabolic activity of the cell (Norris
et al. 2013 ). This potency of the cytoskeleton is related to the association of
metabolic enzymes with the cytoskeleton which results in the mutual ultrastructural
and functional changes presented in this chapter. These changes could be influenced
by the nature of the nucleotides and intermediate metabolites. The evaluation by
mathematical modeling of these complex processes at the molecular level, including
MT dynamics coupled with ligand-mediated enzyme associations, will contribute
enormously to our understanding the moonlighting functions of the enzyme-
cytoskeleton ensemble. Work on this hypothesis is in progress in our laboratory.