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  • Whitley Vistisen posted an update 1 month, 3 weeks ago

    In cultured fibroblasts, plasma membrane transportof free B is calcium independ ent and is sensitive to sulfhydryl inactivation. Sensit ivity to diva lent cationsmay prove to be adistingu ish ing charac ter istic. Sub sequentmovement of B requiresbind ing of B I to a specific periplasmicpro te in. AlthoughtheK, for lysosomal tran sport of B is small compa red to tho se ofotherlysosomal systems, it is relatively large comparedto ex tracellu lar concen trations of B and is several orders of magnitude grea ter than the K. TheK, of these sys tems must, however, be considered in the contextof the proka ryotic and lysosomal env ironmen ts. In contrast, when B is deposited in lysosomesit has a lready been concen tra ted by the in te raction of several high aff inity systems.Itis conceivableth atin sometissues lysosomes serve as in tracellu lar cellular reser voirs of B I and th ata relatively high K, fortran sport is a contr ibuting mechanism forB regulation.Thesi tu ation is appa rently diffe rent in cultu red fib rob lastswhere a lkalin izing agents a re necessary to demonst ra te accumu lation of B in lysosomes.While this may ind ica te that the kinetics of lysosomaltran sport a re tissue specific,theratesof up take and deg radation of the tran scoba lam in I I B I complex and even the numbers of lysosomes may also vary among tissues.We observed a significant overshoot in the uptakeof B at a buffer pH of. F luorescent probe stud ies were not cons is tentwithdiss ipation ofthepH grad ient dur ing B I up take although we cannotexcludethepossibility of small changes in pH. Asimilar overshoot has been observedwi th pro ton grad ien tmed ia ted lysosomaltr an sport of acidic sugars. Tran sport a long thepro ton gr adient en sures th at these produc ts of macromolecular deg radation a re delivered to thecytoplasm.Our results are cons is tentwi th a lysosomal B, carrier th atis sensitive to the pro ton grad ient.The se stud ies have notruledoutthepossibilitiesth atproton move mentor pH induced conformational changes in the carr ier play a role in tran sport. Re sultswi th CCCP while consistentwi th dependence on the pro ton grad ient must be in te rp re ted wi th caution in view of a recent report that CCCP di rectly inh ibits thelysosomal pho spha te carr ier. One other sys tem, the lysosomal cyst ine carr ier, exh ibits the cha rac terist ics ofpH dependence and st imu lation by cations. In this case, tr an sport isst imu la ted by a var ie ty ofdiva lent cations, tr i va lent cations, and polyamines. Itwillbe interest ing to dete rm ine whether themagnesium dependentB IZ system hassimilar properties. Watkins, D, and Rosenblatt, D. S. Am. J. Hum. Genet. Rosenblatt, D. S, Laframboise, R, Pichette, J, Langevin, P, Cooper, B. A, and Costa, T. Ped ia tr ics, Biologic treatments for psoriasis are rarely associated with adverse events. The neurological adverse effects of tumor necrosis factor inhibitors include headache, demyelinating events in the central or peripheral nervous system, and aseptic meningitis.