Sulphydryl group control of sodium-lithium countertransport kinetics: a membrane protein control abnormality in essential hypertension.
Erythrocyte sodium-lithium countertransport (SLC) is an obligatorily coupled equimolar exchange of intracellular sodium or lithium with extracellular sodium or lithium. SLC is partially inhibited by N-ethylmaleimide (NEM) but only when a transported ion (sodium of lithium) is present in the extracellular medium. In essential hypertensive patients with a strong family history of hypertension the Km of SLC for extracellular sodium was lower and Vmax tended to be higher than in normal controls, but the ratio Vmax/Km gave a much clearer distinction between the two groups. After NEM treatment, the remaining SLC activity in normal individuals had a lower Vmax and Km for sodium but Vmax/Km was not affected. In essential hypertensives the remaining SLC activity after NEM again had lowered Vmax and Km but in these patients the Vmax/Km was much lower than in untreated erythrocytes and was then the same as in normal controls. On the assumption that NEM reacts with a -SH group on a membrane protein that regulates SLC, and that the ratio Vmax/Km reflects a rate constant for binding extracellular sodium to the unloaded carrier, the results suggest that (a) essential hypertensives have an increased rate of sodium binding to the transporter and (b) this is due to abnormal behaviour of a membrane -SH group.
Thomas
T H
TH
Department of Medicine (Nephrology), Freeman Hospital, Newcastle-upon-Tyne, UK.
Rutherford
P A
PA
West
I C
IC
Wilkinson
R
R
D000293:Adolescent; D000328:Adult; D017920:Antiporters / Q000097:blood*; D004912:Erythrocytes / Q000378:metabolism; D005033:Ethylmaleimide / Q000494:pharmacology*; D006801:Humans; D006973:Hypertension / Q000235:genetics / Q000378:metabolism*; D007700:Kinetics; D008094:Lithium / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry; D008875:Middle Aged; D012964:Sodium / Q000378:metabolism*
D017920:Antiporters; D008565:Membrane Proteins; C045885:sodium-lithium countertransporter; D008094:Lithium; D012964:Sodium; D005033:Ethylmaleimide