Marques-Porto Rafael, Lebrun Ivo, Pimenta Daniel C
CAT/CEPID, Instituto Butantan, Av Vital Brasil, 1500, São Paulo - SP, 05503-900, Brazil.
Comp Biochem Physiol C Toxicol Pharmacol. 2008 May;147(4):424-33. doi: 10.1016/j.cbpc.2008.01.011. Epub 2008 Feb 5.
Snake venom proteome variation is a well-documented phenomenon, whereas peptidome variation is still relatively unknown. We used a biological approach to explore the inhibitory activities present in the whole venom of Bothrops jararaca that prevents the venom self-proteolysis and/or digestion of the glandular tissue. Although snake venom metallopeptidases have long been known from the biochemical up to the clinical point of view, the mechanisms by which these enzymes are regulated in the reptile's venom gland remain fairly unknown. We have successfully demonstrated that there are three synergistic weak inhibitory mechanisms that are present in the crude venom that are able to abolish the metallopeptidase activity in situ, namely: (i) citrate calcium chelation; (ii) acidic pH and; (iii) enzymatic competitive inhibition by the tripeptide Pyroglutamyl-lysyl-tryptophan. Taken together, these three factors become a strong set-up that inhibits the crude venom metallopeptidase activity as well as a purified metallopeptidase from this same venom. However, this inhibition can be totally reverted by dilution into an optimal pH solution, such as the blood.
蛇毒蛋白质组的变异是一个有充分文献记载的现象，而肽组变异仍相对不为人知。我们采用生物学方法来探究巴西矛头蝮全毒液中存在的抑制活性，这种活性可防止毒液自身蛋白水解和/或腺组织消化。尽管从生化角度到临床角度，蛇毒金属肽酶早已为人所知，但这些酶在爬行动物毒腺中的调节机制仍相当不清楚。我们已成功证明，粗毒液中存在三种协同的弱抑制机制，能够原位消除金属肽酶活性，即：（i）柠檬酸钙螯合；（ii）酸性pH值；以及（iii）三肽焦谷氨酰-赖氨酰-色氨酸的酶竞争性抑制。综合起来，这三个因素形成了一个强大的组合，可抑制粗毒液金属肽酶活性以及来自同一毒液的纯化金属肽酶。然而，通过稀释到最佳pH值溶液（如血液）中，这种抑制作用可完全逆转。
