In vitro and in vivo inhibition of lysyl oxidase byaminopropionitriles
作者:
KennethR. Wilmarth,
JohnR. Froines,
期刊:
Journal of Toxicology and Environmental Health
(Taylor Available online 1992)
卷期:
Volume 37,
issue 3
页码: 411-423
ISSN:0098-4108
年代: 1992
DOI:10.1080/15287399209531680
出版商: Taylor & Francis Group
数据来源: Taylor
摘要:
Inhibition of lysyl oxidase (protein‐lysine 6‐oxidase, EC 1.4.3.13) decreases the rate of collagen and elastin cross‐link formation and produces osteolathyrism in animals. Organic nitriles, including ß‐aminopropionitrile (BAPN), have been shown to irreversibly inhibit lysyl oxidase in vitro. Both BAPN and 3,3'‐iminodipropionitrile (IDPN) have been shown to produce osteolathyric changes when administered to animals. To date compounds that have been reported to inhibit this enzyme possess a primary amine functional group. In this study a series of primary and substituted aminopropionitriles was studied for their ability to inhibit lysyl oxidase activity both in vitro and in vivo. Our results show that of the compounds tested, BAPN was the most potent inhibitor of the enzyme. Reversible inhibition of lysyl oxidase in vitro was found with two secondary aminonitriles, IDPN and monomethy‐laminopropionitrile (MMAPN). There was no inhibition of enzyme activity associated with the tertiary compound 3,3'‐dimethylaminopropionitrile (DMAPN) or propionitrile, a compound lacking an amine functional group. IDPN was found to produce a slight irreversible inhibition of the enzyme both in vitro and in vivo. Pretreatment of rats with pargyline, an inhibitor of monoamine oxidase, was found to increase the inhibitory potential of BAPN (p < .1). Pargyline pretreatment did not alter the inhibitory potential for any of the other aminonitriles tested. These results suggest that the presence of a primary amino functional group is not a strict requirement for inhibition of lysyl oxidase. In addition, reversible and irreversible mechanisms of inhibition may be involved in the production of osteolathyric changes associated with IDPN exposure.
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