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Prog Lipid Res. 1999 Jan;38(1):1-48.

Structure and functional properties of diacylglycerols in membranes.

Author information

1
Departamento de Bioquímica, Universidad del País Vasco, Bilbao, Spain.

Abstract

1. 1,2-Diacyl-sn-glycerols (DAG) are minor components of cell membranes (about 1 mole% of the lipids) and yet they are potent regulators of both the physical properties of the lipid bilayer and the catalytic behaviour of several membrane-related enzymes. 2. In the pure state DAG's present a considerable polymorphism, with several crystalline phases in addition to the neat fluid phase. The most stable crystalline phase is the so-called beta' phase, a monoclinic crystalline form with orthorhombic perpendicular subcell chain packing, in which both acyl chains lie parallel to each other in a hairpinlike configuration about the sn-1 and sn-2 glycerol carbon atoms. The molecules are organized in a bilayer, with the glycerol backbone roughly parallel to the plane of the bilayer, and the acyl chains tilted at approximately 60 degrees with respect to that plane. Acyl chain unsaturation, and particularly a single cis unsaturation, impairs chain packing in mixed-chain DAG's, and this results in an increased number of metastable crystalline phases. 3. DAG's mix with phospholipids in fluid bilayers when their melting temperature is below or close enough to the melting temperature of the bilayer system. When incorporated in phospholipid bilayers, the conformation of DAG is such that the glycerol backbone is nearly perpendicular to the bilayer, with the sn-1 chain extending from the glycerol Cl carbon into the hydrophobic matrix of the bilayer and the sn-2 chain first extending parallel to the bilayer surface, then making a 90 degrees bend at the position of the sn-1 carbonyl to become parallel to the sn-1 chain. DAG's are located in phospholipid bilayers about two CH2 units deeper than the adjacent phospholipids. DAG's mix nonideally with phospholipids, giving rise to in-plane separations of DAG-rich and -poor domains, even in the fluid state. DAG molecules also increase the separation between phospholipid headgroups, and decrease the hydration of the bilayer surface. Also, because the transversal section of the DAG headgroup is small when compared to that of the acyl chains, DAG favours the (negative) curvature of the lipid monolayers, and DAG-phospholipid mixtures tend to convert into inverted nonlamellar hexagonal or cubic phases. 4. A number of membrane enzyme activities are modulated (activated) by DAG, most notably protein kinase C, phospholipases and other enzymes of lipid metabolism. Protein kinase C activation (and perhaps that of other enzymes as well) occurs as the combined result of a number of DAG-induced modifications of lipid bilayers that include: changes in lipid headgroup conformation, interspacing and hydration, changes in the bilayer propensity to form inverted nonlamellar phases, and lateral phase separations of DAG-rich and -poor domains. Among the DAG-activated enzymes, phospholipases C show the peculiarity of yielding the activator DAG as their reaction product, and this allows the self-induced transition from a low- to a high-activity status. 5. DAG's induce or enhance membrane fusion in a number of ways, mainly through partial dehydration of the bilayer surface, increase in lipid monolayer curvature and perhaps lateral phase separation. DAG-increased fusion rates have been demonstrated in several instances of cation-induced fusion of model membranes, as well as in Ca(2+)-induced fusion of chromaffin granules with plasma membrane vesicles. Also phospholipase C has been shown to induce vesicle aggregation and fusion through the catalytic generation of DAG in the bilayers. A rather general property of DAG is that it promotes vesicular or interparticle aggregation. 6. In the living cell, DAG is often generated through phospholipid degradation in response to an extracellular agonist binding a specific receptor in the cell surface. DAG is said to act as an intracellular second messenger. (ABSTRACT TRUNCATED).

PMID:
10396601
DOI:
10.1016/s0163-7827(98)00021-6
[Indexed for MEDLINE]

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