Lecture: Structure and Functions of Lipids

i. Review the grouping of lipids (Fatty acids, acylglycerols,

phosphoacylglycerols, sphingolipids, steroids)

ii. Discuss the structure and the biomedical importance of fatty acids and
cholesterol
1. Free Fatty Acids
a. long, hydrophobic, hydrocarbon chain
b. negatively charged carboxyl group at physiological pH
c. in humans: even number, 16-20 carbons (longer in the brain)
d. detergent character
e. inside of cells esterified in mainly TAGs or membrane lipids
2. Cholesterol
a. found in both leaflets of plasma membrane
b. regulates & stabilizes correct fluidity of PM. Imp due to changed
fatty acid fluidity at diff. temps
c. Hypercholesterolemia- increased blood levels of low-density
lipoproteins (LDLs)
i. Leads to fibrofatty atheroma and Coronary Heart Disease
(CHD)
d. can be used for de novo synthesis of steroid hormones (only in
steroidogenic cells)
i. Adrenal cortex
1. Cortisol, aldosterone, androgens
ii. Ovaries
1. Estradiol
iii. Testes
1. Testosterone

iii. Describe fatty acid structure and discuss the melting points related to
chain length and desaturation and relate its significance in humans
1. Mp of fatty acids
a. increases (stiffer) with chain length
b. decreases with the degree of unsaturation (double bonds)
i. NOTE: degrees of unsaturation trumps length

PALMITATE 16:0 63°C

STEARATE 18:0 70°C
OLEIC ACID 18:1 13°C (monounsat.)
LINOLEIC ACID 18:2, ω-6 -9°C (polyunsat.)
α-LINOLENIC ACID 18:3, ω-3 -17°
ARACHIDONIC ACID 20:4, ω-6 -50°C
EPA (EICOSAPENTAENOIC ACID) 20:5, ω-3 -17°C
DHA (DOCOSAHEXAENOIC ACID) 22:6, ω-3 -45 TO -50°C
 iv. Discuss the biological importance of dietary essential fatty acids and
describe in detail the structures of linoleic acid ( 6) and -linolenic acid
( 3)

Importance of dietary essential fatty acids

 Precursors of physiological important fatty acids
 Components in biological membranes, modifying the fluidity by themselves
or by longer fam members (20:4, ω-6/Arachidonic acid and 22:6,ω-3/DHA)
 Pass through BBB
 Arachidonic acid, EPA, and DHA found in breast milk and ability to enter
developing brain in infants
 Deficiencies rares, can lead to scaly dermatitis, hair loss, poor wound healing,
visual and neurological abnormalities
 TPN (total parenteral nutrition) intravenous form to administer dietary
essential acids

Linoleic acid ( 6) and -linolenic acid ( 3) are dietary EFA’s

o Linoleic Acid (18:2 6)  Arachidonic Acid (20:4 6)
 Eicosanoids are synthesized from a fatty acid with 20 carbons
(prostaglandins, thromboxane, leukotrienes)
o α-Linoleic Acid (18:3 3) EPA (20:5 3)  DHA( 22:6 3)
 The -3 fatty acids are important for brain, vision, &
cardiovascular health
 DHA in phospholipids of the brain provides a high fluid
microenvironment. DHA is important for brain functions and
the visual cycle in the retina.

v. Discuss the grouping of fatty acids into the ω-6 and ω-3 families and
describe in general the synthesis of arachidonic acid and of
docosahexaenoic acid (DHA)

Elongation occurs at C#1, the carboxyl carbon (COOH)

ω-family is determined by counting backwards from methyl end (last carbon)

vi. Describe the structures and functions of triacylglycerols, and distinguish

between phospholipids and glycolipids with examples for each

TAGS
o Totally nonpolar
o Glycerol backbone
o Abt 40% of normal diet
o Main storage form of fatty acids
o Synthesis mainly occurs in the liver, adipose tissue, lactating mammary glands
and intestinal mucosal cells
Glycerolipids and Sphingolipids are Polar Lipids found in human membranes.

GLYCEROLIPIDS
 Lipids containing phosphate are phospholipids
 Most phospholipids contain a glycerol backbone (glycerophospholipid)
 Pos1-saturated fatty acycl ester
 Pos2-unsaturated fatty acyl ester
 Pos3-binds the phosphoryl group with the specific head group
 ***exception is: Sphingomyelin, which is a phosphor-sphingolipid**

SPHINGOLIPIDS
 Lipids containing sugars are glycolipids
 Glycolipids contain a sphingosine backbone (glycosphingolipids)
 Sphingosine with a fatty acid joined to its amino group is named ceramide
 Can be grouped into neutral or acidic glycolipids

vii.

 Phosphatidylcholine (PC) aka Lecithin

 Phospholipid
 Major component of membrane lipids
 Overall charge is 0
 In PM, mainly outer leaflet
 Can be formed by:
 Hepatocytes using dietary choline
 3x methylation of PE
 provides monolayer in lipoproteins
 secreted by liver into bile for cholesterol transport and dietary lipid digestion
 provides lung surfactant in alveoli of lung
 modification to dipalmitoyl-PC
 used for synthesis of sphingomyelin (which also has phosphoryl choline head
group)
 PC is precursor for the
lipid part of lung surfactant
(90% lipid, 10%
protein)
released by alveolar Type II cells by active transport by specific
ABC-transporters.
 Two esterified saturated fatty acids, palmitates, are needed in order to
generate an extra- cellular fluid that prevents alveolar collapse during
exhalation.
 Mainly dipalmitoyl-phosphatidylcholine (disaturated) is released together
with monosaturated PC
 Phosphatidylethanolamine (PE)
 Phospholipid
 Major component of membrane lipids
 Overall charge is 0
 In PM, mainly inner leaflet
Plasmalogen
 Phospholipid analogues
 Contain long-chain fatty alcohol ether linkage at carbon-1 of the glycerol
backbone
 Fatty alcohol group has a double bond between its carbons 1 and 2 (vinyl-
ether)
 PC analogue mainly found in the heart
 PE analogue mainly found in nerve tissue
 Phosphatidylserine (PS)
 Overall negative charge
 Inner leaflet of PM
 Exposure on surface of cells is an early event of apoptosis leading to removal
by macrophages
 Phosphatidylinositol (PI)
 Inner leaflet of PM
 Contains arachidonic acid which can be released for eicosanoid synthesis
directly by phospholipase A2 or indirectly by phospholipase C (PLC)
 Can be phosphorylated to PIP2 and cleaved by PLC to generate the second
messengers DAG and inositol triphosphate (IP3)
 PIP2  cleaved by PLC  DAG and IP3
o In the Ca++ second messenger system
o IP3 releases from PM and binds to receptor that opens ER calcium
ion channel
 Cardiolipin
 Special phospholipid (antigenic)
 In eukaryotes, mainly in inner mitochondrial membrane; also found in
bacteria
 Needed for respiratory complexes of electron transport chain
 Aka di-phosphatidylglycerol
 Contains 4 fatty acyl esters, mainly linoleic acid
 antibodies raised against Treponema pallidum (bacterium that causes
Syphilis) recognize this antigenic phospholipid
 Deficiency of cardiolipin leads to BARTH’S SYNDROME, rare but severe
cardiomyopathy
 Sphingolipids
 Polar membrane lipids, found mostly in outer leaflet of PM
 Serve in intercellular communication, as antigenic determinant of ABO blood
groups
 Form myelin sheath surrounding nerves of CNS and PNS
 Synthesis starts with palmitoyl CoA and serine with coenzyme, pyridoxal
phosphate (PLP)
 N-acyl-sphingosine (ceramide) is precursor formed forall sphingolipids
o Ceramide
 Found on top layer of skin as barrier to help retain moisture,
together with cholesterol and fatty acids
 Decreased levels of ceramides can lead to eczema and dryness

of skin
 Sphingomyelin
 Major structural phospholipid in nerve tissues, RBCs, and ocular lenses
 Insulator of nerve fibers as part of myelin sheath
 Involved in signal transduction
 Lipid rafts in PM
 May lead to apoptosis after cleavage to ceramide
 PC is used to form sphingomyelin (heads are the same)
 Multiple sclerosis (demyelination)
 Neiman-Pick disease (lysosomal storage disease)
 Glycosphingolipids (cerebrosides and globosides)
 Antigenic, neutral
o Cerebrosides
 Ceramide and one sugar
o Globosides
 Ceramide and 2+ sugars
 Both found in brain and peripheral nervous tissue, with high
concentration in myelin sheath
 Degradation of all sphingolipids takes places in lysosomes. Defective
degradation leads to lysosomal storage disease, sphingolipidoses.

viii. Discuss role of lung surfactant in respiratory distress syndrome

-In preterm infants, deficiency of lung surfactant can lead to RDS

-Lung maturity of fetus is predicted by lecithin/sphingomyelin ratio
Ratio > or = 2 is related to maturity
-RDS also found in adults due to damage of cells producing lung surfactant
 COMPOSITION FUNCTION
phosphatidylcholine

phosphatidylethanolamine

plasmalogens

phosphatidylserine

phosphatidylinositol

cardiolipin

sphingomyelin

Cerebrosides

globosides

gangliosides