A combined transcriptomic, proteomic and metabolic analysis provided an overview of the main changes occurring in gene expression during maize kernel development. It allowed identifying genes expressed at each developmental stage and the shift occurring from one stage to the other. A major change occurred at the transition from lag phase where final grain size is established to grain filling where starch and protein are accumulated in the endosperm storage tissue. Although the expression of enzymes involved in storage product synthesis is dominant in the accumulation phase, the proportion of protein destination and protein synthesis gene products is still important. Detailed proteomic analysis of metabolism shows an upsurge of the pyruvate-Pi-dikinase (PPDK) in the late filing period (21 DAP onwards) that is interpreted as a switch in the starch/protein balance. This hypothesis is based on biochemical arguments involving the negative effect of PPi on the ADP-glucose pyrophosphorylase (Agpase), a key-enzyme of starch synthesis, and the role of phosphoenolpyruvate (PEP) in aromatic amino acid synthesis. It is substantiated by the data on the Opaque-2 gene encoding a transcription factor with pleiotropic effect affecting lysine content and carbohydrate metabolism, thus acting indirectly on starch/amino acid ratio. The direct effect of O2 on PPDK gene expression provides a clue for explaining the competition between C and N metabolisms. This epistatic relationship between PPDK and O2 is further supported by quantitative and association genetics.