Advances in the Biosynthetic Pathways and Application Potential of Plasmalogens in Medicine.

Yulong Zhou,Ning Yu,Zhaonan Yang,Jie Zhao,Bing Tian,Zhenming Xie

doi:10.3389/fcell.2020.00765

Abstract

Plasmalogens are a special class of polar glycerolipids containing a vinyl-ether bond and an ester bond at sn-1 and sn-2 positions of the glycerol backbone, respectively. In animals, impaired biosynthesis and regulation of plasmalogens may lead to certain neurological and metabolic diseases. Plasmalogens deficiency was proposed to be strongly associated with neurodegenerative and metabolic diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD), and appropriate supplement of plasmalogens could help to prevent and possibly provide therapy of these diseases. Plasmalogens evolved first in anaerobic bacteria with an anaerobic biosynthetic pathway. Later, an oxygen-dependent biosynthesis of plasmalogens appeared in animal cells. This review summarizes and updates current knowledge of anaerobic and aerobic pathways of plasmalogens biosynthesis, including the enzymes involved, steps and aspects of the regulation of these processes. Strategies for increasing the expression of plasmalogen synthetic genes using synthetic biology techniques under specific conditions are discussed. Deep understanding of plasmalogens biosynthesis will provide the bases for the use of plasmalogens and their precursors as potential therapeutic regimens for age-related degenerative and metabolic diseases.

Highlights

Plasmalogens (1-O-alk-1 -enyl 2-acyl glycerol phospholipids and glycolipids), called plasmenyl phospholipid and plasmenyl glycolipids, are a special group of polar lipids, accounting for approximately 18–20 mol% of the total phospholipids in cell membranes of almost all mammalian
Serum plasmalogen levels have been used to diagnose and successfully stratify Alzheimer’s disease (AD) patients (Wood et al, 2015). These illustrate the importance of comprehensive understanding of the functions and biosynthesis of plasmalogens, which might be developed as a potential medicine for AD
For the branch of PtdGro synthesis, CDP-DAG is converted to phosphatidylglycerol 3-phosphate (PGP) by PGP synthase (PgsA) and the 3-phosphate can be removed by a PGP phosphatase (PgpA or PgpB) to generate PtdGro (Dowhan, 1997)

Summary

INTRODUCTION

Plasmalogens (1-O-alk-1 -enyl 2-acyl glycerol phospholipids and glycolipids), called plasmenyl phospholipid and plasmenyl glycolipids, are a special group of polar lipids, accounting for approximately 18–20 mol% of the total phospholipids in cell membranes of almost all mammalian They are the constituents of biomembranes, which has a diversity of functions such as cell homeostasis, signaling and neural transmission (Ferlay et al, 2015; Dean and Lodhi, 2018). Serum plasmalogen levels have been used to diagnose and successfully stratify AD patients (Wood et al, 2015) These illustrate the importance of comprehensive understanding of the functions and biosynthesis of plasmalogens, which might be developed as a potential medicine for AD. The significance of recently found important genes and strategies for increasing the production and application potential of plasmalogens in medicine are discussed

PLASMALOGENS BIOSYNTHESIS IN ANAEROBIC BACTERIA

Function descriptions

CONCLUSION

Findings

AUTHOR CONTRIBUTIONS