Relationships among carbohydrate intermediate metabolites and DNA damage and repair in yeast from a systems biology perspective

Glucose and fructose are major dietary carbohydrates that are essential for general metabolism. The elevated consumption of these two monosaccharides by the human population is related to the development of pluri-metabolic syndromes (e.g., diabetes mellitus and obesity). Glucose and fructose are metabolized by specific biochemical pathways to generate energy and metabolites. Many of these metabolites are mono- and bi-phosphorylated compounds, which renders them likely to generate reactive carbonyl species (RCS). Under physiological conditions, RCS react non-enzymatically with macromolecules and small molecules by means of Maillard reactions, forming stable glycated/fructated compounds called advanced glycation end products (AGEs). DNA and dNTPs are prone to react with RCS, forming DNA- and dNTP-AGEs, and many of these compounds are genotoxic and/or mutagenic. Unfortunately, little is understood about the genotoxicity and/or mutagenicity of carbohydrate intermediate metabolites or their interactions with DNA repair and carbohydrate metabolic-associated proteins. To elucidate these associations between carbohydrate metabolic pathways, DNA repair mechanisms, and dNTP-/DNA-AGEs, a systems biology study was performed by employing algorithms to mine literature data and construct physical protein-protein interactions. The results obtained in this work allow us to construct a model suggesting that yeast carbohydrate metabolic-associated enzymes activate different mechanisms for DNA repair and dNTP synthesis and act during DNA replication to protect the genome against the effects of RCS. (C) 2008 Elsevier B.V. All rights reserved.