Leukotriene A4 hydrolase: a zinc metalloenzyme.
Purified human leukotriene A4 hydrolase is shown to contain 1 mol of zinc per mol of enzyme, as determined by atomic absorption spectrometry. The enzyme is inhibited dose-dependently by the chelating agents 8-hydroxy-quinoline-5-sulfonic acid, and 1,10-phenanthroline with KI values of about 2 and 8 x 10(-4) M, respectively, whereas dipicolinic acid and EDTA are ineffective in this respect. The inhibition by 1,10-phenanthroline is time-dependent, and at a concentration of 5 mM, 50% inhibition of enzyme (3 x 10(-7) M) occurs after about 15 min. The zinc atom of leukotriene A4 hydrolase can be removed by dialysis against 1,10-phenanthroline which results in loss of enzyme activity. The catalytic activity is almost completely restored by the addition of stoichiometric amounts of Zn2+ or Co2+.
Haeggström
J Z
JZ
Department of Physiological Chemistry, Karolinska Institute, Stockholm, Sweden.
Wetterholm
A
A
Shapiro
R
R
Vallee
B L
BL
Samuelsson
B
B
D000595:Amino Acid Sequence; D000626:Aminopeptidases / Q000378:metabolism; D001051:Apoenzymes / Q000097:blood*; D003035:Cobalt / Q000097:blood; D004851:Epoxide Hydrolases / Q000097:blood*; D006801:Humans; D007668:Kidney / Q000201:enzymology; D007700:Kinetics; D007962:Leukocytes / Q000201:enzymology*; D008666:Metalloendopeptidases / Q000097:blood*; D008969:Molecular Sequence Data; D013054:Spectrophotometry, Atomic; D013379:Substrate Specificity; D013820:Thermolysin / Q000378:metabolism; D015032:Zinc / Q000097:blood*
D001051:Apoenzymes; D003035:Cobalt; D004851:Epoxide Hydrolases; D000626:Aminopeptidases; D008666:Metalloendopeptidases; D013820:Thermolysin; D015032:Zinc; C043134:leukotriene A4 hydrolase