Analysis of a Lipid Biosynthesis Protein Family and Phospholipid Structural Variations

Michihiro Tanaka [1](
Yuki Moriya [1](
Susumu Goto [1](
Minoru Kanehisa [1][2](

[1]Bioinformatics Center, Institute for Chemical Research, Kyoto University, Uji, Kyoto 611-0011, Japan
[2] Human Genome Center, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan


Glycerophospholipids are major structural lipids in cellular membrane systems and play key roles as suppliers of the first and second messengers in the signal transduction and molecular recognition processes. The distribution of lipid components differs among organelles and cells. The distribution is controlled by two pathways in lipid metabolism: de novo and remodeling pathways. Glycerophospholipids including arachidonic and stearic acids are mostly produced in the remodeling pathway, whereas lipid chains are reconstructed from those synthesized in the de novo pathway. Recently lysophospholipid acyltransferases have been isolated as key enzymes in the remodeling pathway, and the substrate specificity has been investigated in terms of the chemical substructures of glycerophospholipids, such as the type of head groups and the length of aliphatic chains. These experimental studies have been reported for specific organisms, and only two representative sequence motifs are known for acyltransferases: a general pattern and the pattern for membrane-bound O-acyltransferase (MBOAT). Here we attempt to correlate the sequence patterns and the substrate specificity of lysophospholipid acyltransferases in 89 eukaryotic genomes in order to understand the roles of this enzyme family and underlying glycerophospholipid structural variations. Using phylogenetic and domain analyses, the lysophospholipid acyltransferase family was divided into 18 subtypes. Furthermore, we examined the occurrence of identified subtypes in eukaryotic genomes, and found the expansion of these subtypes in vertebrates. These findings may provide clues to understanding structural variations and distributions of glycerophospholipids in different organisms.

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Japanese Society for Bioinformatics