Membrane glycerophospholipids

Excitatory Amino Acid Receptors and Their Association with Neural Membrane Glycerophospholipid Metabolism... 

Farooqui A. A., Horrocks L. A., and Farooqui T. (2007a). Interactions between neural membrane glycerophospholipid and sphingolipid mediators a recipe for neural cell survival or suicide. J. Neurosci. Res. 85 1834-1850. 

Fig. 1. Structures of membrane glycerophospholipids. R1 and Ft2 represent hydrocarbon chains of fatty acids.

Roles Fatty acids have four major biological roles 1. They are components of membranes (glycerophospholipids and sphingo- lipids) 2. Several proteins are covalently modified by fatty acids 3. They act as energy stores (triacylglycerols) and fuel molecules 4. Fatty acid derivatives serve as hormones and intracellular second messengers. 

Voelker, D. R. 2003. New perspectives on the regulation of inter-membrane glycerophospholipid traffic. J. Lipid Res. 44 441-449. 

Glutamate-mediated calcium influx results in stimulation arachidonic acid release from neural membrane glycerophospholipids. This release is catalyzed by CPLA2 and PLC/DAG-lipase pathway (McIntosh et al., 1998 Schuhmann et al., 2003 Shohami et al., 1987, 1989 Wei et al., 1982 Dhillon et al., 1996 Homayoun et al., 1997, 2000). Arachidonic acid release occurs in traumatic as well as fluid percussion models of brain injury (FPI). Enzymic oxidation of arachidonic acid generates prostaglandins, leukotrienes, and thromoboxanes whereas non-enzymic oxidation produces isoprostanes and ROS which include superoxide and hydroxyl radicals (Farooqui and Horrocks, 2007). 

Neural membrane glycerophospholipids are synthesized from three dietary components polyunsaturated fatty acids, uridine monophosphate (UMP), and choline (Farooqui and Horrocks, 2007). Administration of above nutrients increases the level of glycerophospholipids, specific pre- or postsynaptic proteins, and the number of dendritic spines - a requirement for new synapse formation (Wurtman et al., 2009 Kamphnis and Wurtman, 2009). These effects are markedly enhanced when animals receive all three compounds together. This multi-nutrient approach in animals has also been shown to decrease A plaque burden, improve learning and memory through increased cholinergic neurotransmission, and have a neuroprotective effect in several mouse models of AD (Wurtman et al., 2009 ... 

The initial step in eicosanoid production by CYPs, COX, and LOX enzymes is liberation of polyunsaturated fatly acids (PUFAs), such as AA, from plasma membranes. Fatty acids in vivo are primarily esterified to the sn-2 position of cell membrane glycerophospholipids [1]. These fatly acids act as important structural components that regulate membrane fluidity and permeability. Storage of phospholipid-bound fatly acids in the membrane also provides a reservoir for lipids during the initial step in eicosanoid biosynthesis [1,4,5]. Physiological stressors such as ischemia or inflanunation can activate phosphohpase A2 (PLA2) enzymes that cleave AA from the phospholipid and make it available for oxidative metabolism by the three major enzyme systems (Fig. 13.1) [6-9]. 

C14 0 Tetradecanoic acid Myristic acid Named after the nutmeg Myristica fragrans, found in membrane glycerophospholipids... 

PA is a metabolic intermediate in the biosynthetic/degradation pathways of more complex glycerophospholipids. It usually represents less than 1% of total membrane lipids but plays a critical role in signal transduction, due to the xmique ionization properties of its phosphate group (see Chapter 3). Membrane glycerophospholipids are derived from PA by condensation with an organic alcohol (general formula X-OH). Phosphatidylcholine (PC), the most abundant membrane lipid, results from the condensation of choline with PA (Fig. 1.14). 

Similarly, you can write the structures of phosphatidylethanolamine PE and phosphatidyl-serine PS (Fig. 1.16). Now you know how to write the structure of the three main membrane glycerophospholipids. At pH 7, both PC and PE are zwitterions (i.e., bear a positive and a negative charge). In contrast, PS has one positive and two negative charges, so that this lipid is globally anionic. ... 

Phosphatidic acid is a key intermediate metabolite in the S5mthesis pathways of all membrane glycerophospholipids, including phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), as well as phosphatidylinositol (PI) and its phosphorylated... 

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