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Titolo:
Abnormal sodium stimulation of carnitine transport in primary carnitine deficiency
Autore:
Wang, YH; Meadows, TA; Longo, N;
Indirizzi:
Emory Univ, Dept Pediat, Div Med Genet, Atlanta, GA 30322 USA Emory Univ Atlanta GA USA 30322 iat, Div Med Genet, Atlanta, GA 30322 USA
Titolo Testata:
JOURNAL OF BIOLOGICAL CHEMISTRY
fascicolo: 27, volume: 275, anno: 2000,
pagine: 20782 - 20786
SICI:
0021-9258(20000707)275:27<20782:ASSOCT>2.0.ZU;2-0
Fonte:
ISI
Lingua:
ENG
Soggetto:
ORGANIC CATION/CARNITINE TRANSPORTER; GLUCOSE-GALACTOSE MALABSORPTION; NA+/PROLINE TRANSPORTER; ESCHERICHIA-COLI; OCTN2; COTRANSPORTER; MUTATIONS; RESIDUES; IDENTIFICATION; CATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
26
Recensione:
Indirizzi per estratti:
Indirizzo: Longo, N Emory Univ, Dept Pediat, Div Med Genet, 2040 Ridgewood Dr, Atlanta, GA 30322 USA Emory Univ 2040 Ridgewood Dr Atlanta GA USA 30322 a, GA 30322 USA
Citazione:
Y.H. Wang et al., "Abnormal sodium stimulation of carnitine transport in primary carnitine deficiency", J BIOL CHEM, 275(27), 2000, pp. 20782-20786

Abstract

Primary carnitine deficiency is an autosomal recessive disorder of fatty acid oxidation characterized by hypoketotic hypoglycemia and skeletal and cardiac myopathy. It is caused by mutations in the sodium-dependent carnitinecotransporter OCTN2, The majority of natural mutations identified in this and other Na+/solute symporters introduce premature termination codons or impair insertion of the mutant transporter on the plasma membrane. Here we report that a missense mutation (E452K) identified in one patient with primary carnitine deficiency did not affect membrane targeting, as assessed withconfocal microscopy of transporters tagged with the green fluorescent protein, but reduced carnitine transport by impairing sodium stimulation of carnitine transport. The natural mutation increased the concentration of sodium required to half-maximally stimulate carnitine transport (K-Na) from the physiological Value of 11.6 to 187 mM. Substitution of Glu(452) with glutamine (E452Q), aspartate (E452D), or alanine (E452A) caused intermediate increases in the K-Na. Carnitine transport decreased exponentially with increased K-Na. The E452K mutation is the first natural mutation in a mammalian cotransporter affecting sodium-coupled solute transfer and identifies a noveldomain of the OCTN2 cotransporter involved in transmembrane sodium/solute transfer.

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Documento generato il 11/07/20 alle ore 11:18:18