Dynamics of sulfur amino acids in mammalian brain: assessment of the astrocytic-neuronal cysteine interaction by a mathematical hybrid model.
A mathematically hybrid model was used to analyze three mechanisms by which cysteine could be produced in the brain to be used as preferential substrate in the synthesis of neuronal glutathione. In that way, the fluxes of sulfur-compounds at the brain-blood barrier were integrated with their transport in astrocytes and neurons, and with their metabolism in astrocytes. We concluded that cysteine, in contrast with its precursor cystine, would not be taken up from the blood at the blood-brain barrier, but instead it must be lost continuously from astrocytes. Cysteine efflux is produced because the uptake of cystine in astrocytes is much greater than their cysteine demand to synthesize glutathione, hypotaurine and taurine. Once in the interstitial parenchyma, cysteine would be taken for the neurons, as backwardly by the endothelial cells. Remarkably, a close sulfur-macro balance can be maintained only if the surplus of the produced cysteine is transferred from the endothelial cells to the blood together with significant amounts of other sulfur-compounds, probably taurine and hypotaurine. In addition, the results obtained shown that alternative mechanisms of cysteine generation (i.e., nonenzymatic-thiol-disulfide exchange reaction, enzymatic cleavage of the glutathione effluxed from astrocytes) are not quantitatively significant under physiological conditions, in situ.
Guebel
Daniel V
DV
Biotechnology Counseling Services, Av San Martín 4927, (1417) Buenos Aires, Argentina.
Torres
Néstor V
NV
D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001812:Blood-Brain Barrier / Q000502:physiology; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D003545:Cysteine / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D008433:Mathematics; D008959:Models, Neurological; D009474:Neurons / Q000378:metabolism*; D013457:Sulfur Compounds / Q000737:chemistry / Q000378:metabolism; D013654:Taurine / Q000737:chemistry / Q000378:metabolism
D013457:Sulfur Compounds; D013654:Taurine; D005978:Glutathione; D003545:Cysteine