Glutathione, S-substituted glutathiones, and leukotriene C4 as substrates for peptidylglycine alpha-amidating monooxygenase.
Glutathione, S-substituted glutathiones, and leukotriene C4 as substrates for peptidylglycine alpha-amidating monooxygenase.
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谷胱甘肽、S-取代的谷胱甘肽和白三烯 C4 作为肽基甘氨酸 α-酰胺化单加氧酶的底物。
DOI：
10.1016/s0003-9861(02)00730-0
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发表时间：
2003
影响因子：
3.9
通讯作者：
Merkler,DavidJ
中科院分区：
文献类型：
--
作者：
Miller,LauraAaron;Baumgart,LauraE;Chew,GeoffreyH;deLong,MitchellA;Galloway,LamarC;Jung,KyungWoon;Merkler,KathleenA;Nagle,AdvaitS;Poore,DerekD;Yoon,CheolHwan;Merkler,DavidJ
大多数肽激素的C-末端α-酰胺部分是在双功能肽基甘氨酸α-酰胺化单加氧酶（PAM）催化的反应中，通过甘氨酸延伸的前体的翻译后切割产生的。谷胱甘肽和S-烷基化谷胱甘肽具有C-末端甘氨酸，因此是PAM的潜在底物。PAM与谷胱甘肽、一系列S-烷基化谷胱甘肽和白三烯C4的加成导致O2的消耗和相应酰胺化肽和乙醛酸的产生。该反应分两步进行，中间形成C-末端α-羟基甘氨酸延伸肽。酰胺化谷胱甘肽（γGlu-Cys-amide）是谷胱甘肽S-转移酶的相对较差的底物，V/K值为谷胱甘肽的1.3%。含有倒数第二个疏水或含硫氨基酸的肽底物对PAM催化的酰胺化表现出最高的（V/K）appvalues。S-烷基化谷胱甘肽在倒数第二个位置结合了这两种功能，S-癸基谷胱甘肽在本报告中描述的底物中具有最高的（V/K）appof。
The C-terminal α-amide moiety of most peptide hormones arises by the posttranslational cleavage of a glycine-extended precursor in a reaction catalyzed by bifunctional peptidylglycine α-amidating monooxygenase (PAM). Glutathione and the S-alkylated glutathiones have a C-terminal glycine and are, thus, potential substrates for PAM. The addition of PAM to glutathione, a series of S-alkylated glutathiones, and leukotriene C4results in the consumption of O2and the production of the corresponding amidated peptide and glyoxylate. This reaction proceeds in two steps with the intermediate formation of a C-terminal α-hydroxyglycine-extended peptide. Amidated glutathione (γGlu-Cys-amide) is a relatively poor substrate for glutathione S-transferase with a V/K value that is 1.3% of that for glutathione. Peptide substrates containing a penultimate hydrophobic or sulfur-containing amino acid exhibit the highest (V/K)appvalues for PAM-catalyzed amidation. The S-alkylated glutathiones incorporate both features in the penultimate position with S-decylglutathione having the highest (V/K)appof the substrates described in this report.