Chapter 2 Section 2 LIPIDS
1. Simple lipids: Esters of fatty acids with alcohols; sub-groups are fats (fatty acids + glycerol) and waxes (fatty acids + monohydric alcohols of high molecular weight)
2.3.4. PHOSPHOLIPIDS
Phospholipids are predominantly membrane lipids in both prokaryotes and eukaryotes, required for both membrane structure and function. They are fatty acyl esters characterized by the presence of a phosphate residue. Depending on the nature of the alcohol residue present, phospholipids are of two main types: phosphoglycerides (glycerol) and sphingomyelins (sphingosine).
Phosphoglycerides
The parent compound of the phosphoglycerides is phosphatidic acid in which a phosphate residue is located on C-3 of a diglyceride. The acyl group on C-1 is generally saturated (C16-C18), while C-2 bears an unsaturated fatty acid (C18-C20). The presence of the phosphate group makes phosphatidic acid a chiral, highly charged and polar compound.
Fig 2.2.14 A. Structural formulae of L-Phosphatidic acid.
choline ethanolamine serine inositol
Fig 2.2.14 B. Alcohol moieties attach to phosphatidic acid giving phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine or phosphatidylinositol
(Source: Murray et al, 2003, p 115 fig 14-8)
A second –OH group of the phosphate residue can be esterified with another highly polar alcohol moiety (shaded blue) to give a phosphatidyl derivative. In the common phosphoglycerides, this substituent group is choline, ethanolamine, serine, inositol, glycerol phosphate or even another phosphatidyl group. A phosphodiester bond thus links the glyceride backbone with the substituent group. Note that any given phosphoglyceride (e.g. phosphatidylcholine) actually represents a molecular species, all members of which have the same overall structure but differ in their specific fatty acyl constituents.
The phosphoglycerides are internal zwitterions. The alcohol moiety determines the sign and magnitude of the charge. At neutral pH, phosphatidylcholine and phosphatidylethanolamine are
cationic, phosphatidylinositol is anionic while phosphatidylserine is neutral. This is of great significance in determining the permeability properties of cell membranes which face a continuous bombardment of diverse molecules.
Most phosphoglycerides are amphipathic, with a highly polar, hydrophilic “head” represented by the phosphate group or its derivatives on C-3, and two non-polar, hydrophobic “tails” of acyl esters on C-1 and C-2. The non-polar parts of phosphoglyceride molecules tend to associate together, while the polar parts interact with the aqueous environment of body fluids. Hence, the phospholipids tend to self-orient at liquid-water interfaces, a property of tremendous biological significance in membranes and other lipid assemblies.
A. ‘Clothes peg’ shape of a phosphoglyceride B. Phosphoglycerides in a membrane bilayer
Fig 2.2.15. A. ‘Clothes peg’ shape of a phosphoglyceride showing polar ‘head’ and non-polar ‘tails’
B. Orientation of phosphoglyceride molecules in a membrane bilayer. Polar ‘heads’ are directed outwards towards the aqueous medium while non-polar tails are directed inwards.
(Source: A. Lodish et al, 2003,; B. Murray et al, 2003, p 418 fig 41-5)
The different phosphoglycerides have their own unique and varied distribution in cells, tissues and organs. Phosphatidylcholine (lecithin) is the most abundant membrane lipid. It is also a major source of choline (for acetylcholine) and labile methyl groups. Dipalmitoyl lecithin is a major constituent of surfactant in the lungs; its absence causes respiratory distress syndrome, particularly in the newborn. Phosphatidylethanolamine (cephalin) and phosphatidylserine are also important membrane constituents in most tissues. Diphosphatidylglycerol (cardiolipin) is required for cytochrome oxidase and for phosphate transport in the inner mitochondrial membrane. Inositol phospholipid interacts with supramolecular protein complexes in cell signalling. It is the source of phosphatidylinositol 3,4,5-triphosphate (IP3) and diacylglycerol (DAG) which are 2nd messengers in hormone action.
Plasmalogens are a group of phosphoglycerides in which the acyl residue on C-1 is replaced by an alkenyl chain, attached by an ether bond. The alcohol moiety is ethanolamine, choline, serine or inositol. Plasmalogens constitute 50% of phospholipids in the heart and 10% of those in the brain and muscle. Ether-linked phospholipids are not hydrolyzed by phospholipases and this may be of biological significance. Thus, tetraether lipids in membranes of archebacteria are stable at
atherosclerosis. Phospholipases in snake and insect venom cause hemolysis by hydrolyzing membrane phospholipids.
CH2O C H2 N H+ 3 CH2 OP-
O O 2O C H C H C O R' O
O C R
H C H
CH2O.
CH2O OC H2 2+ N(
CH OP-
O
C O
C R C
O R' O
)3 3
Phosphatidylethanolamine Phosphatidylcholine (lecithin)
C H2OC H C HR C H
C O R' O
CH2O N H+ 3 C H2CH2 OP-
O O
. R
CH2O C O
C H
)3 H3 CH2O OC H2 2+
N(
CH OP-
O
C O
H
Ethanolamine plasmalogen Lysolecithin
A. B.
Fig 2.2.16. Comparison of the structures of (A) phosphatidylethanolamine and ethanolamine plasmalogen and (B) phosphatidylcholine and lysolecithin (the altered groups are indicated in pink).
All lipids which are acyl esters of the amino alcohol sphingosine (= 4-sphigenene), are referred to as sphingolipids. The attachment of a single fatty acyl residue to sphingosine, gives ceramide, the parent compound of all sphingolipids. Sphingolipids with phosphate groups are sphingomyelins, while those with sugar substituents and no phosphate group are glycosphingolipids. We will deal with the sphingomyelins under “phospholipids” and take up the glycosphingolipids under “glycolipids”.
Sphingosine Ceramide
acy l group
choline
O CH3( CH2)12CH CH CH CH N
OH H
CH2
O O P O-
CH2CH2N+ ) ( CH3 3 C
O R
phosphoric diester
A. Sphingomyelin
Sphingosine Ceramide
acy l group
CH3( CH2)12CH CH CH CH N OH H
CH2
C O
CH( OH () CH )2 21CH3
Galactose
B. Glycosphingolipid (acyl group from cerebronic acid)
Fig 2.2.17. Comparative structures of a sphingomyelin and a glycosphingolipid (cerebroside).
Sphingomyelins
A sphingomyelin is obtained by attachment of phosphocholine or phosphoethanolamine to ceramide. Its polar ‘head’ is the phosphocholine moiety, while the two non-polar ‘tails’ are the hydrocarbon chains of the acyl group and sphingosine. Take a look at the unexpected similarity in shape of a sphingomyelin molecule to a phosphoglyceride.
Fig 2.2.18. Chemical and space-filling models of phosphoglyceride (left) and sphingomyelin (right) to show similarity in shape (Source: Nelson and Cox, 2005, p 354 fig 10-13)
Sphingomyelins are present in neural tissues. They constitute the myelin sheath, which electrically insulates an axon. De-myelination causes a debilitating disease called multiple sclerosis.
Sphingomyelins are also potent regulators of protein kinases and are involved in cell division, differentiation, migration and apoptosis.