A constraint-based modelling approach to metabolic dysfunction in Parkinson's disease.

One of the hallmarks of sporadic Parkinson's disease is degeneration of dopaminergic neurons in the pars compacta of the substantia nigra. The aetiopathogenesis of this degeneration is still not fully understood, with dysfunction of many biochemical pathways in different subsystems suggested to be involved. Recent advances in constraint-based modelling approaches hold great potential to systematically examine the relative contribution of dysfunction in disparate pathways to dopaminergic neuronal degeneration, but few studies have employed these methods in Parkinson's disease research.

Identification of active elementary flux modes in mitochondria using selectively permeabilized CHO cells.

Metabolic compartmentation is a key feature of mammalian cells. Mitochondria are the powerhouse of eukaryotic cells, responsible for respiration and the TCA cycle. We accessed the mitochondrial metabolism of the economically important Chinese hamster ovary (CHO) cells using selective permeabilization.

Non-stationary 13C metabolic flux analysis of Chinese hamster ovary cells in batch culture using extracellular labeling highlights metabolic reversibility and compartmentation.

Background: Mapping the intracellular fluxes for established mammalian cell lines becomes increasingly important for scientific and economic reasons. However, this is being hampered by the high complexity of metabolic networks, particularly concerning compartmentation.

Results: Intracellular fluxes of the CHO-K1 cell line central carbon metabolism were successfully determined for a complex network using non-stationary 13C metabolic flux analysis.

Dynamics of growth and metabolism controlled by glutamine availability in Chinese hamster ovary cells.

The physiology of animal cells is characterized by constantly changing environmental conditions and adapting cellular responses. Applied dynamic metabolic flux analysis captures metabolic dynamics and can be applied to industrially relevant cultivation conditions. We investigated the impact of glutamine availability or limitation on the physiology of CHO K1 cells in eight different batch and fed-batch cultivations.

Eukaryotic metabolism: measuring compartment fluxes.

Metabolic compartmentation represents a major characteristic of eukaryotic cells. The analysis of compartmented metabolic networks is complicated by separation and parallelization of pathways, intracellular transport, and the need for regulatory systems to mediate communication between interdependent compartments. Metabolic flux analysis (MFA) has the potential to reveal compartmented metabolic events, although it is a challenging task requiring demanding experimental techniques and sophisticated modeling.