The Phosphobase Methylation Pathway in Caernorhabditis elegans: A New Route to Phospholipids in Animals

Soon      Goo Lee; Joseph      M. Jez

Abstract

Parasitic nematodes are a major cause of human health problems with an estimated 1 billion people infected worldwide by these organisms. Identifying biochemical targets that differ between the parasite and host species is essential for finding effective new anti-parasitic molecules. The free-living nematode Caenorhabditis elegans is a powerful model system for experiments in genetics and developmental biology needed to achieve this goal; however, in-depth understanding of metabolic processes in this organism is limited as it still contains unexplored biochemical pathways. Eukaryotes, including nematodes and humans, share many similar metabolic pathways, which makes specific targeting of nematode parasites challenging. Recent studies suggest that C. elegans and other nematodes may use a plant-like pathway as the major biosynthetic route to phosphatidylcholine. In this pathway, a pair of phosphoethanolamine methyltransferases (PMT) catalyze the sequential methylation of phosphoethanolamine to phosphocholine, which can be incorporated into phosphatidylcholine. RNAi experiments demonstrate that both PMT are required for normal growth and development of C. elegans. Because the PMT are highly conserved across nematode parasites of humans, livestock, and plants, as well as in protozoan parasites, understanding how these enzymes function and the identification of inhibitors will aid in the development of new anti-parasite compounds of potential medical, veterinary, and agricultural value.

Keywords: Caernorbabditis elegans, nematode, phosphobase methylation, phospholipids, methyltransferase, phosphoethanolamine, phosphocholine, phosphatidylserine decarboxylase, phosphodimethylethanolamine, phosphatidylcholine