Glycerolipids Glycerol - 3 - phosphate

FIGURE 25.18 Synthesis of glycerolipids in eukaryotes begins with the formation of phosphatidic acid, which may be formed from dihydroxyace-tone phosphate or glycerol as shown. 

Glycerolipids are derivatives of glycerol and fatty acids. Most brain glycerolipids are derivatives of phos-phatidic acid (PtdOH), which is diacylated sn-glycerol-3-phosphate. The notation sn refers to stereochemical... 

Figure 21-3 Major pathways of synthesis of fatty acids and glycerolipids in the green plant Arabidopsis. The major site of fatty acid synthesis is chloroplasts. Most is exported to the cytosol as oleic acid (18 1). After conversion to its coenzyme A derivative it is converted to phosphatidic acid (PA), diacylglycerol (DAG), and the phospholipids phosphatidylcholine (PC), phosphatidylinositol (PI), phosphatidylglycerol (PG), and phosphatidylethanolamine (PE). Desaturation also occurs, and some linoleic and linolenic acids are returned to the chloroplasts. See text also. From Sommerville and Browse.106 See also Figs. 21-4 and 21-5. Other abbreviations monogalactosyldiacylglycerol (MGD), digalactosyldiacylglycerol (DGD), sulfolipid (SL), glycerol 3-phosphate (G3P), lysophosphatidic acid (LPA), acyl carrier protein (ACP), cytidine diphosphate-DAG (CDP-DAG).

In cell extracts we have been unable to detect glyceraldehyde 3-phosphate dehydrogenase, glycerol kinase or glyceraldehyde kinase, consistent with a non-phosphorylated glycerol as the glycerolipid precursor [2,16]. 

L.E. Hammond, P.A. Gallagher, and S. Wang, et al., Mitochondrial glycerol-3-phosphate acyltransferase-deficient mice have reduced weight and liver triacylglycerol content and altered glycerolipid fatty acid composition. Mol. Cell. Biol., 2002, 22, 8204-8214. 

In the plastids, acyltransferases provide a direct route for entrance of acyl groups from ACP to membrane lipids. Since this is the standard pathway for phosphatidic acid synthesis in E. coli and cyanobacteria, both the enzymes of phosphatidic acid synthesis in plastids and the glycerolipid backbones they produce are termed prokaryotic . In both chloroplasts and non-green plastids, the glycerol-3-phosphate acyltransferase is a soluble enzyme that, unlike the E. coli enzyme, shows preference for 18 1-ACP over 16 0-ACP. The lysophosphatidic acid acyltransferase, which is a component of the inner envelope of plastids, is extremely selective for 16 0-ACP. The presence of a 16-carbon fatty acid at the... 

Fig. 5. Biosynthesis of membrane phospholipids from alkyldihydroxyacetone-P (alkyl-DHAP), the first detectable intermediate formed in the biosynthetic pathway for ether-linked glycerolipids. Enzymes catalyzing the reactions are (1) NADPH alkyl-DHAP oxidoreductase, (II) acyl-CoA 1 -alkyl-2-lyso-sn-glycero-3-phosphate acyltransferase, (III) l-alkyl-2-acyl-in-glycero-3-phosphate phosphohydrolase, (IV) ATP 1-alkyl- /i-glycerol phosphotransferase, (V) CDP-choline l-alkyl-2-acyl-sn-glycerol cholinephosphotransferase (dithiothreitol-sensitive), (VI) CDP-ethanolamine l-alkyl-2-acyI-sn-glycerol ethanolaminephosphotransferase, and (VII) acyl-CoA 1 -alkyl-2-acy 1-OT-glycerol acyltransferase.

Total syntheses of glycerolipids using protective groups for both the glycerol and phosphate groups usually start with l,2-isopropylidene-5 n-glycerol. This is readily obtained by oxidative cleavage of the bis-acetonide of D-manni-... 

The low incorporation of [%[-glycerol into tumoral lipids would indicate a decrease of the glycerophosphate pathway for the glycerolipid biosynthesis. Nevertheless a lack in the glycerol activation to sn-glycerol-3-phosphate by the tumdral tissue cannot be ruled out. 

Figure 3.3 Enzyme systems associated with glycerolipid formation, (a) Glycerol kinase (EC 2.7.1.30) (b) glycerol-3-phosphate acyltransferase (EC 2.3.1.15) (GPAT) (c) 1-acyl-glycerol-3-phosphate acyltransferase (EC 2.3.1.51) (LPAAT) (d) phosphatidate phosphatase (EC 3.1.3.4) (e) diacylglycerol acyltransferase (EC 2.3.1.20) (DAGAT) (f) cholinephosphotransferase (EC 2.7.8.2) (CPT) (g) 1-acylglycerophosphocholine acyltransferase (EC 2.3.1.23).

Glycerol 3-phosphate acyl transferase (G3P-AT) and 1-acylglycerol 3-phosphate acyl transferase (LPA-AT), which catalyse the first two steps in course of de novo biosynthesis of glycerolipids, are known enzymic activities not only of plastids and microsomes (Frentzen 1986) but also of mitochondria from higher plants (Douce 1971, Vick and Beevers 1977, Sparace and Moore 1979). In mitochondria of castor bean endosperm the two enzymic activities were localized in both the inner and outer membrane (Sparace and Moore 1979), but little is known about the enzymic properties. 

Acyl-(acyl-carrier protein) glycerol-3-phosphate acyl transferase (glycero-P acyltransferasc) in higher-plant chloroplasts transfers the acyl group from acyl-(acyl-carrier protein) to the C-1 position of glycerol 3-phosphate to synthesize 1-acylglycerol 3-phosphate. Since this reaction is the first step of glycerolipid synthesis in the chloroplasts, it is of special interest to study this enzyme. 

Zufferey and Mamoun 2005. The initial step of glycerolipid metabolism in Leishmania major promastigotes involves a single glycerol-3-phosphate acyltransferase enzyme important for the synthesis of triacylglycerol but not essential for virulence. Molecular Microbiology, 56 800-810. 

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