Using L-cysteate and tcysteinesulfinate as model substrates, we characterize here a transport system, both in culturerda t hepatocytes and human skin fibroblasts, serving for thea nions glutamate and aspartate, but not for the dipolar species glutamic and aspartic acids. This system appears to be accompanied by a second, lower affinity system for the anionic forms, which is also Na’-dependent; this lower affinity system applies at least to glutamate. These systems show the usual degree of preference for L- over D-glutamate and, in the fibroblast, for L- over DL-a-aminoadipate. D-ASpartate proved nearly as inhibitory to the uptake of Lcysteate or t-aspartate, however, as did L-aspartate itself, a comparison recalling a similar stereoselective anomaly discovered by Pall in Neurospora (Pall, M. (1976) Biochim Biophys. Acta 211, 513-520). We conclude that this anomaly arises from the ability of the two substrate carboxylate groups tob ond in the spatial order eithera # for the L-isomer or &a for the D-isomer and also to bond in the order a,y for L-glutamate, but scarcely in the order y,a for D-glutamate. A major lack of inhibition by D-cysteate, whichm ight be expected to bind like aspartate in the inverted order, shows, however, that thetw o anionic groups are not recognized in identical manners by the two corresponding subsites, Precedent for a chemical difference in these two subsites is available from transport systems for neutral aand p-amino acids. A strong transporti nhibition of the hepatocyte system by 3-aminoglutarate shows that an a,a relation between the amino group and eitheor f the carboxylate groups of the anionic amino acid is not required. The above anomaly in stereoselectivity is compared with a corresponding one, applying to the reactions of aspartic acid and asparagine, versus glutamic acid and glutamine, with System L for neutral amino acid transport in the Ehrlich cell. A weak pHdependent inhibition of the uptake of anionic amino acids by cysteine can be associated with its unique mode of conversion to an anionic species.
|Tipologia ministeriale:||Articolo su rivista|
|Appare nelle tipologie:||1.1 Articolo su rivista|