Porcine liver aminopeptidase B. Substrate specificity and inhibition by amino acids.
Porcine liver aminopeptidase B[EC 3.4.11.6] is highly specific for hydrolysis of beta-naphthylamides of basic L-amino acids; the Km values for L-arginine beta-naphthylamide and L-lysine beta-naphthylamide were 0.035 and 0.12 mM, respectively. The enzyme was inhibited by various alpha-amino acids. Among basic amino acids, L-homoarginine and L-arginine were the most potent inhibitors, L-lysine and L-norarginine (alpha-amino-gamma-guanidinobutyric acid) being less inhibitory. Hydrophobic amino acids also inhibited the enzyme competitively. This suggests that there is a hydrophobic region that binds the side chain of the substrates or inhibitors in the specificity site of the enzyme. Studies on the inhibitions by L-arginine derivatives showed that blocking of the alpha-carboxyl or the alpha-amino group reduced the inhibitory effect of L-arginine. Porcine liver aminopeptidase B was not inhibited by puromycin, whereas bestatin inhibited the enzyme competitively with a Ki value of 1.4 X 10(-8) M. This enzyme had no kinin-converting activity.
D000596:Amino Acids / Q000494:pharmacology*; D000626:Aminopeptidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology; D006709:Homoarginine / Q000494:pharmacology; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D008099:Liver / Q000201:enzymology*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D013552:Swine
D000596:Amino Acids; D006709:Homoarginine; C029772:arginine beta-naphthylamide; D001120:Arginine; D000626:Aminopeptidases; C019721:aminopeptidase B; D007930:Leucine; C012211:ubenimex