Platelet-activating factor acetylhydrolase.
Platelet-activating factor (PAF) is one of the most potent lipid mediators and is involved in a variety of physiological events. The acetyl group at the sn-2 position of its glycerol backbone is required for its biological activity, and deacetylation of PAF induces loss of activity. The deacetylation reaction is catalyzed by PAF-acetylhydrolase (PAF-AH). A series of biochemical and enzymological studies have revealed that there are at least three types of PAF-AH in mammals, namely the intracellular type I and II and plasma type. Type I PAF-AH is a G-protein-like complex 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 circumstantial evidence is accumulating supporting the idea that the catalytic subunits are also involved in microtubule function, it is still not known what role PAF plays in the process and whether PAF is a native 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 roles as scavengers of oxidized phospholipids which are thought to be involved in diverse pathological processes, including disorganization of membrane structure and PAF-like proinflammatory actions. In this chapter, author focuses on the structures and possible biological functions of intracellular PAF-AHs.
Arai
Hiroyuki
H
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Japan. harai@mol.f.u-tokyo.ac.jp
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000818:Animals; D001921:Brain / Q000201:enzymology; D020134:Catalytic Domain; D019281:Dimerization; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008223:Lymphoma / Q000201:enzymology; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D010741:Phospholipases A / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity
D007527:Isoenzymes; D008869:Microtubule-Associated Proteins; D010972:Platelet Activating Factor; D021122:Protein Subunits; D010741:Phospholipases A; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C084102:PAFAH1B1 protein, human