Inhibition of hyaluronidases and chondroitinases by fatty acids.
The inhibitory effects of various fatty acids on three hyaluronidases (h-ST, h-SH and h-SD) and four chondroitinases (c-ABC, c-B, c-ACI and c-ACII) were examined, and their structure-activity relationships and mechanism of action were studied. The fatty acids used in this experiment showed various inhibitory activities against the enzymes. None of the fatty acids did not inhibit h-ST and h-SH. The saturated fatty acids (C10:0 to C22:0) showed very weak or no inhibition against h-SD, c-ABC, c-B, c-ACI and c-ACII but the unsaturated fatty acids (C14:1 to C24:1) with one double bond strongly inhibited the enzymes, and the inhibitory potency increased with increase in carbon chain length of the fatty acids. In contrast, the increase in number of double bonds caused a decrease in inhibitory potency against the enzymes. The position of the double bond and the stereochemistry of the cis-trans form of oleic acid (C18:1) did not influence the inhibitory potency against the enzymes. Carboxyl and hydroxyl groups in the fatty acid molecule were concerned in the inhibition of c-ACI. Among the fatty acids, eicosatrienoic acid (C20:3) generally inhibited h-SD, c-ABC, c-B and c-ACI, and nervonic acid (C24:1) was a potent inhibitor of c-ACII, and the fatty acids inhibited the enzymes in a noncompetitive manner.
Suzuki
Keitarou
K
Laboratory of Pharmaceutical Microbiology, Faculty of Pharmaceutical Sciences, Kumamoto University, Japan.
Terasaki
Yoshikazu
Y
Uyeda
Masaru
M
D000818:Animals; D001426:Bacterial Proteins; D002810:Chondroitinases and Chondroitin Lyases / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D005227:Fatty Acids / Q000737:chemistry / Q000494:pharmacology*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D006821:Hyaluronoglucosaminidase / Q000037:antagonists & inhibitors*; D020128:Inhibitory Concentration 50; D007700:Kinetics; D012756:Sheep; D013329:Structure-Activity Relationship
D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D005227:Fatty Acids; D005231:Fatty Acids, Unsaturated; D006821:Hyaluronoglucosaminidase; D002810:Chondroitinases and Chondroitin Lyases