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María Ángeles Pajares

Figure 6. Actualized version of the model proposed for redox regulation of MATs. The proposal includes the most significant data
regarding normal liver (left) and damaged liver (right). Mean GSH/GSSG ratios in each situation are included, together with the changes
detected in expression due to gene methylation or stabilization/destabilization of the mRNAs. Effects on the proteins include those
derived from increased levels of the cofactors, altered association patterns and subcellular distribution rendering finally, high or low SAM
levels in normal and damaged livers respectively.

Redox regulation is probably the best-known samples and tools are available. In the near future, work in
mechanism controlling MAT function in disease states, but this field will require a larger effort on the solution of
still questions regarding how copper exerts its effects on structures, the role of post-translational modifications, the
these enzymes remain unsolved. Additionally, the role of identification of protein-protein interactions and
other actors in redox stress, such as NAD+/NADH or development of imaging techniques able to evaluate
NADP+/NADPH ratios, should be explored in the whole subcellular levels of metabolites. Null mice models are
methionine cycle and special attention should be paid on valuable tools for the development of the field, but certain
subcellular distribution. The number of enzymes of this aspects concerning the proteins themselves cannot be
pathway found in the nucleus is increasing (SAHH, analyzed in animals that lack their expression. Subcellular
GNMT, MATs) and their role in this compartment is localization and its relationship with pathology lay within
underexplored. Possibilities such as moonlighting this category.
activities cannot be forgotten, neither the protein-protein
interactions in which they might be involved. 7. ACKNOWLEDGEMENTS

6. CONCLUSION The work reviewed in this manuscript has been
supported by grants of the Ministerio de Economía y
In the last 20 years our group has developed protocols Competitividad (PB94-0087, PM97-0064, BMC2002-
and tools for the study of MATs and the methionine cycle 00243, BMC2005-00050, BFU2008-00666/BMC,
and, as a result of this effort, new data have been obtained BFU2009-08977/BMC) and Fondo de Investigación
both in vitro and in vivo. Altogether, these results have Sanitaria (FIS 01/1077, C03/08, PI05/0563).
shown the existence of new levels of regulation for MATs
that might be key for understanding their role in disease, 8. REFERENCES
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242 @Real Academia Nacional de Farmacia. Spain