Lack of regulation of aromatic L-amino acid decarboxylase in intact bovine chromaffin cells.
Aromatic l-amino acid decarboxylase (AADC) is the second enzyme in the catecholamine biosynthetic pathway, and its activity is generally considered not to be limiting, and therefore not involved, in regulating flux through this pathway. Recent studies showing that its activity can be regulated in vivo and that the enzyme can be phosphorylated and activated in vitro have raised the possibility that AADC may play more than an obligatory role in catecholamine biosynthesis. In the present study, the phosphorylation and activity of AADC was evaluated relative to that of tyrosine hydroxylase (TH; the first and rate-limiting enzyme in the pathway) in intact bovine chromaffin cells. Treatment of chromaffin cells with elevated potassium, acetylcholine, phorbol dibutyrate, forskolin, or okadaic acid each increased 32P incorporation into TH (after metabolic labeling of ATP pools with 32P(i)) and TH activity. In contrast, as measured in matched samples, 32P incorporation into AADC was not detected and none of the treatments altered AADC activity. Thus, that AADC can be phosphorylated and activated in vitro has questionable physiological significance.
Waymire
Jack C
JC
Department of Neurobiology and Anatomy, University of Texas Houston Medical School, Houston, Texas, USA.
Haycock
John W
JW
D000109:Acetylcholine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D020536:Enzyme Activators / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019319:Okadaic Acid / Q000494:pharmacology; D010703:Phorbol Esters / Q000494:pharmacology; D010761:Phosphorus Radioisotopes; D010766:Phosphorylation; D011188:Potassium / Q000494:pharmacology; D011233:Precipitin Tests; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D020536:Enzyme Activators; D004791:Enzyme Inhibitors; D010703:Phorbol Esters; D010761:Phosphorus Radioisotopes; D005576:Colforsin; D019319:Okadaic Acid; D000255:Adenosine Triphosphate; D014446:Tyrosine 3-Monooxygenase; D001142:Aromatic-L-Amino-Acid Decarboxylases; D000109:Acetylcholine; D011188:Potassium