NEW FUNCTION OF PHOSPHOLIPASE A

脑细胞内血小板活化因子乙酰水解酶（PAF-AH）亚型I是由相互同源的α1和α2亚基组成的复杂酶家族的成员，这两个亚基都具有催化活性，以及B亚基。我们先前证明，一种催化亚基α1的表达是发育调节的，导致在脑发育期间催化复合物从α1/α2转换（Manya，H.，Aoki，J.，Watanabe，M.，阿达奇，T.，Asou，H.，Inoue，Y.，Arai，H.，和Inoue，K.（1998）J.Biol.Chem.273，18567 - 18572）。在这项研究中，我们探讨了三种可能的催化二聚体，α1/α2和α2/α2同源二聚体的生化差异，表现出不同的底物特异性，从α1/α2异源二聚体，这两个都表现出类似的底物特异性。在1-O-烷基-2-乙酰基磷脂中，α2/α2同二聚体水解PAF和1-O-烷基-2-乙酰基-sn-甘油基-3-磷酸磷脂酰乙醇胺（AAGPE）的效率最高。相比之下，α1/α1和α1/α2水解1-O-烷基-2-乙酰基-sn-甘油基-3-磷酸磷脂酸（AAGPA）的效率高于PAF。AAGPE是这些酶的最差底物。β亚基与所有三种催化二聚体结合，但以催化二聚体组成依赖性方式调节酶活性。β亚基强烈促进α2/α2同源二聚体的酶活性，但抑制α1/α1同源二聚体的酶活性，而对α1/α2异源二聚体的酶活性影响不大。最近在孤立的无脑序列患者中鉴定出的（His 149至Arg 149）突变体β丧失了与催化复合物结合或调节其酶活性的能力。PAF-AH亚型I的酶活性可以通过改变催化亚基的组成和操纵β亚基以多种方式调节。

Brain intracellular platelet-activating factor acetylhydrolase (PAF-AH) isoform I is a member of a family of complex enzymes composed of mutually homologous α1 and α2 subunits, both of which account for catalytic activity, and the b subunit. We previously demonstrated that the expression of one catalytic subunit, α1, is developmentally regulated, resulting in a switching of the catalytic complex from α1/α2 during brain development (Manya, H., Aoki, J., Watanabe, M., Adachi, T., Asou, H., Inoue, Y., Arai, H., and Inoue, K. (1998) J. Biol. Chem. 273, 18567 - 18572). In this study, we explored the biochemical differences in three possible catalytic dimers, α1/α2, and α2/α2 homodimer exhibited different substrate specificity from the α1/α2 heterodimer, both of which showed similar substrate specificity. The α2/α2 homodimer hydrolyzed PAF and 1-O-alkyl-2-acetyl-sn-glycero-3-phosphophatidylethanolamine (AAGPE) most efficiently among 1-O-alkyl-2-acetyl-phospholipids. In contrast, both α1/α1 and α1/α2 hydrolyzed 1-O-alkyl-2-acetyl-sn-glycero-3-phosphophatidic acid (AAGPA) more efficiently than PAF. AAGPE was the poorest substrate for these enzymes. The β subunit bound to all three catalytic dimers but modulated the enzyme activity in catalytic dimer composition-dependent manners. The βsubunit strongly accelerated the enzyme activity of the α2/α2 homodimer but rather suppressed the activity of the α1/α1 homodimer and had little effect on that of the α1/α2 heterodimer. The (His 149 to Arg 149) mutant β, which has been recently identified in isolated lissencephaly sequence patients, lost the ability to either associate with the catalytic complexes or modulate their enzyme activity. The enzyme activity of PAF-AH isoform I may be regulated in multiple ways by switching the composition of the catalytic subunit and by manipulating the β subunit.