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Kinetoplastea such as trypanosomatid parasites contain specialized peroxisomes that uniquely contain enzymes of the glycolytic pathway and other parts of intermediary metabolism and hence are called glycosomes. Their specific enzyme content can vary strongly, quantitatively and qualitatively, between different species and during the parasites' life cycle. The correct sequestering of enzymes has great importance for the regulation of the trypanosomatids' metabolism and can, dependent on environmental conditions, even be essential. Glycosomes also play a pivotal role in life-cycle regulation of Trypanosome brucei, as the translocation of a protein phosphatase from the cytosol forms part of a crucial developmental control switch. Many glycosomal proteins are differentially phosphorylated in different life-cycle stages, possibly indicative for unique forms of activity regulation, whereas many kinetic activity regulation mechanisms common for glycolytic enzymes are absent in these organisms. Glycosome turnover occurs by autophagic degradation of redundant organelles and assembly of new ones. This may provide the trypanosomatids with a manner to rapidly and efficiently adapt their metabolism to the sudden, major nutritional changes often encountered during the life cycle. This could also have helped facilitating successful adaptation of kinetoplastids, at multiple occasions during evolution, to their parasitic life style.

One current challenge in metabolic systems biology is to map out the regulation networks that control metabolism. From progress in this area, we conclude that non-transcriptional mechanisms (e.g. metabolite-protein interactions and protein phosphorylation) are highly relevant in actually controlling metabolic function. Furthermore, recent results highlight more functions of enzymes and metabolites than currently appreciated in genome-scale metabolic reconstructions, thereby adding another level of complexity. Combining experimental analyses and modeling efforts we are also beginning to understand how metabolic behavior emerges. Particularly, we recognize that metabolism is not simply a dull workhorse process but rather takes very active control of itself and other cellular processes, rendering true system-level understanding of metabolism possibly more difficult than for other cellular systems.