Platelet-activating factor acetylhydrolase (PAF-AH).
Platelet-activating factor (PAF) is one of the most potent lipid messengers involved in a variety of physiological events. The acetyl group at the sn-2 position of its glycerol backbone is essential for its biological activity, and its deacetylation induces loss of activity. The deacetylation reaction is catalyzed by PAF-acetylhydrolase (PAF-AH). A series of biochemical and enzymological evaluations revealed that at least three types of PAF-AH exist in mammals, namely the intracellular types I and II and a plasma type. Type I PAF-AH is a G-protein-like complex consisting of two catalytic subunits (alpha1 and alpha2) and a regulatory beta subunit. The beta subunit is a product of the LIS1 gene, mutations of which cause type I lissencephaly. Recent studies indicate that LIS1/beta is important in cellular functions such as induction of nuclear movement and control of microtubule organization. Although substantial evidence is accumulating supporting the idea that the catalytic subunits are also involved in microtubule function, it is still unknown what role PAF plays in the process and whether PAF is an endogenous substrate of this enzyme. Type II PAF-AH is a single polypeptide and shows significant sequence homology with plasma PAF-AH. Type II PAF-AH is myristoylated at the N-terminus and like other N-myristoylated proteins is distributed in both the cytosol and membranes. Plasma PAF-AH is also a single polypeptide and exists in association with plasma lipoproteins. Type II PAF-AH as well as plasma PAF-AH may play a role as a scavenger of oxidized phospholipids which are thought to be involved in diverse pathological processes, including disorganization of membrane structure and PAF-like proinflammatory action. In this review, we will focus on the structures and possible biological functions of intracellular PAF-AHs.
Arai
Hiroyuki
H
Graduate School of Pharmaceutical Sciences, University of Tokyo, Hongo-Bunkyo-ku, Tokyo 113-0033, Japan. harai@mol.f.u-tokyo.ac.jp
Koizumi
Hiroyuki
H
Aoki
Junken
J
Inoue
Keizo
K
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000818:Animals; D020134:Catalytic Domain; D006801:Humans; D008223:Lymphoma / Q000201:enzymology; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008958:Models, Molecular; D010741:Phospholipases A / Q000737:chemistry / Q000378:metabolism*; D013379:Substrate Specificity
D008869:Microtubule-Associated Proteins; D010741:Phospholipases A; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C084102:PAFAH1B1 protein, human