pH-dependent release of catecholamines from tyrosine hydroxylase and the effect of phosphorylation of Ser-40.
Bovine adrenal tyrosine hydroxylase (TH) is isolated in a partially inhibited state with the feed-back inhibitors adrenaline and noradrenaline tightly coordinated to high-spin (S = 5/2) Fe(III) at the active site. In addition to the charge-transfer interaction with iron, an additional charged group in the polypeptide chain, with an apparent pKa of about 5.3 at 4 degrees C, is involved in the binding of catecholamines. Protonation of this group increases the pseudo-first order rate constant for the dissociation of the TH-[3H]noradrenaline complex more than 100-fold at 4 degrees C. At pH 7.0 and 30 degrees C, phosphorylation of Ser-40 causes a 6-fold increase in the rate constant for this dissociation.
Haavik
J
J
Department of Biochemistry, University of Bergen, Norway.
Martínez
A
A
Flatmark
T
T
D000311:Adrenal Glands / Q000201:enzymology*; D000818:Animals; D001665:Binding Sites; D002417:Cattle; D004837:Epinephrine / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D009638:Norepinephrine / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D012694:Serine / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
D012694:Serine; D014446:Tyrosine 3-Monooxygenase; D009638:Norepinephrine; D004837:Epinephrine