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Titolo:
Two-step mechanism of phlorizin binding to the SGLT1 protein in the kidney
Autore:
Oulianova, N; Falk, S; Berteloot, A;
Indirizzi:
Univ Montreal, Fac Med, Dept Physiol, Membrane Transport Res Grp, Montreal, PQ H3C 3J7, Canada Univ Montreal Montreal PQ Canada H3C 3J7 rp, Montreal, PQ H3C 3J7, Canada
Titolo Testata:
JOURNAL OF MEMBRANE BIOLOGY
fascicolo: 3, volume: 179, anno: 2001,
pagine: 223 - 242
SICI:
0022-2631(20010201)179:3<223:TMOPBT>2.0.ZU;2-J
Fonte:
ISI
Lingua:
ENG
Soggetto:
D-GLUCOSE COTRANSPORT; BORDER-MEMBRANE-VESICLES; AFFINITY NA+/GLUCOSE COTRANSPORTER; RAPID FILTRATION APPARATUS; EPITHELIAL-CELL LINES; SUGAR-TRANSPORT; RADIATION-INACTIVATION; PROXIMAL TUBULE; INTESTINAL NA+; SODIUM;
Keywords:
transport kinetics; inhibitor binding mechanisms; cotransport models; rapid filtration technique; membrane vesicles (rabbit kidney cortex);
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
65
Recensione:
Indirizzi per estratti:
Indirizzo: Berteloot, A Univ Montreal, Fac Med, Dept Physiol, Membrane Transport Res Grp, CP 6128,Succursale Ctr Ville, Montreal, PQ H3C 3J7, Canada Univ Montreal CP 6128,Succursale Ctr Ville Montreal PQ Canada H3C 3J7
Citazione:
N. Oulianova et al., "Two-step mechanism of phlorizin binding to the SGLT1 protein in the kidney", J MEMBR BIO, 179(3), 2001, pp. 223-242

Abstract

The relationships between phlorizin binding and Nac-glucose cotransport were addressed in rabbit renal brush-border membrane vesicles. At pH 6.0 and 8.6, high affinity phlorizin binding followed single exponential kinetics. With regard to phlorizin concentrations, the binding data conformed to simple Scatchard kinetics with lower apparent affinities of onset binding (K-di= 12-30 mum) compared to steady-state binding (K-de = 2-5 muM)? and the first-order rate constants demonstrated a Michaelis-Menten type of dependencewith K-m values identical to K-di. Phlorizin dissociation from its receptor sites also followed single exponential kinetics with time constants insensitive to saturating concentrations of unlabeled phlorizin or D-glucose, but directly proportional to Na+ concentrations. These results prove compatible with homogeneous binding to SGLT1 whereby fast Na+ and phlorizin addition on the protein is followed by a slow conformation change preceding further Na+ attachment, thus occluding part of the phlorizin-bound receptor complexes. This two-step mechanism of inhibitor binding invalidates the recruitment concept as a possible explanation of the fast-acting slow-binding paradigm of phlorizin, which can otherwise be resolved as follows: the rapid formation of an initial collision complex explains the fast-acting behavior ofphlorizin with regard to its inhibition of glucose transport however, because this complex also rapidly dissociates in a rapid filtration assay, the slow kinetics of phlorizin binding are only apparent and reflect its slow isomerization into more stable forms.

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Documento generato il 17/01/21 alle ore 18:20:55