Paraoxonase polymorphism in rabbits.
Paraoxonase in serum and liver of rabbits and cattle was investigated. In serum the two substrates paraoxon and phenylacetate are exclusively hydrolyzed by alpha-lipoprotein-bound paraoxonase. In rabbit liver paraoxon is hydrolyzed only by paraoxonase, while phenylacetate is hydrolyzed by paraoxonase (20%) and additionally by an organophosphate sensitive carboxylesterase (B-Esterase), which is responsible for 80% of total liver phenylacetate hydrolysis. Phenyl acetate hydrolysis by B-Esterase of rabbit liver was shown to be inhibited by paraoxon and by mipafox covalently in a time and concentration dependent manner. Rabbit serum exhibits by far the highest serum paraoxonase activity (2.6 +/- 0.66 U/ml) of all vertebrate species tested up to now, while rabbit liver contains only 0.5 +/- 0.2 U/g fresh weight. In cattle extremely high paraoxonase activity is found in liver (2.8 U/g), while bovine serum contains only 0.2 U/g. The paraoxonase activity ratio (hydrolysis rate paraoxon: phenylacetate x 1000) in cattle does not show interindividual variation (activity ratio 4.0 +/- 0.4, correlation coefficient 0.996, P < 0.001). In contrast, the paraoxon/phenylacetate hydrolysis ratio of rabbit paraoxonase in serum as well as in liver does vary considerably between individuals. In cross-bred rabbits paraoxonase activity ratios from three to ten are found. In a strain of pure-bred New Zealand White rabbits three polymorphic serum paraoxonase phenotypes could be clearly differentiated by the activity ratio. By analogy with the human paraoxonase polymorphism, the rabbit paraoxonase isotypes were classified as paraoxonase A (activity ratio 3.8-4.3), AB (ratio 5.5-6.0) and B (ratio 7.3-8.6). The corresponding frequencies of the three isotypes were 40, 35 and 25%.
Department of Biochemistry, Georg-August-University, Göttingen, Germany.
R
R
Zech
R M
RM
Severin
J M
JM
Chemnitius
K
K
Nebendahl
D000818:Animals; D043303:Aryldialkylphosphatase; D043182:Carboxylesterase; D002265:Carboxylic Ester Hydrolases / Q000097:blood / Q000235:genetics / Q000378:metabolism; D002417:Cattle; D004950:Esterases / Q000097:blood* / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D006868:Hydrolysis; D007527:Isoenzymes / Q000097:blood / Q000235:genetics / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D008297:Male; D010261:Paraoxon / Q000097:blood / Q000378:metabolism; D010648:Phenylacetates / Q000378:metabolism; D011110:Polymorphism, Genetic; D011817:Rabbits
D007527:Isoenzymes; D010648:Phenylacetates; D004950:Esterases; D002265:Carboxylic Ester Hydrolases; D043182:Carboxylesterase; D043303:Aryldialkylphosphatase; C025136:phenylacetic acid; D010261:Paraoxon