Lipids of Physiologic Significance:

Include: fats, steroids, waxes, oils related more by physical than structural
qualities
Relatively insoluble in water
Soluble in nonpolar solvents eg. Ether
Imp dietary constituents: high energy & fat-soluble vitamins & essential fatty acids
Fat: stored in adipose tissue heat insulation under skin and some organs
Nonpolar lipids: electrical insulators Rapid propagation of APs in myelinated neurons
Lipoproteins: transport lipids in blood
Lipids can be simple or complex:
SIMPLE lipids: esters of fatty acid with various alcohols
FATS: esters of F.As with glycerol (oils =fats in liquid state)
Waxes: esters of F.As with higher molec weight monohydric alcohols
COMPLEX lipids: have added groups to the simple lipids
Phospholipids: contain a phosphoric acid residue in addition to F.As and alcohol. Frequently
contain Nitrogenous bases eg. Glycerophospholipids:alchol is glycerol and sphingolipids:
alcohol is sphingosine
Glycolipids (glycosphingolipids GSLs ) lipids containing F.A, sphingolipid and carbohydrate
Others: sulfolipids, aminolipids
Precursor and derived lipids: F.As, Glycerol, steroids, fatty aldehydes, ketone bodies,
hydrocarbons, lipid soluble vitamins, other alcohols and hormones
Neutral lipids: uncharges eg, acylglycerols, cholesterol and cholesteryl esters

Most fatty acids are found in the body as esters in fats and oils.
But also in unesterified form as Free Fatty Acids used for transportation in the plasma
Fatty acids in natural fats contain even number of carbon atoms
Chain may be saturated or unsaturated
Unsaturated Fatty acids may be further subdivided:
1. Monounsaturated one double bond
2. Polyunsaturated 2 or more double bonds. Divided into 2 groups w-3 or w-6 depending on
where 1
st
double bond occurs.
3. Eicosanoids powerful hormone-like molecules in most mammalian tissues. Are derived from
eicosa (20-carbon) polyenoic F.As. Comprise: prostanoids, leukotrienes (LTs),
prostaglandins(PGs), prostacyclins (PGIs) and thromboxanes (TXs)
Prostaglandins: exist in mammalian tissue and act as local hormones with important physiologic and
pharmacologic activities. Are Synthesized in vivo by cyclization of the center of the carbon chain of
eicosanoic polyunsaturated F.As and form a cyclopentane ring. Eg arachidonic acid(synth from linoleic
acid). Prostaglandins mediate inflammation, pain, induce sleep and regulate blood coagulation and
reproduction.
Thromboxanes: similar but have the cyclopentane ring interrupted by an O atom (oxane ring). Have
thrombus forming potential
Leukotrienes and lipoxins: formed via lipoxygenase pathway. Presence of 3 or 4 conjugated double
bonds. Leukotrienes cause bronchoconstriction and potent proinflammatory agents an play a part in
asthma.

Unsaturated Fatty acids: show geometric isomerism. CIS and Trans isomerism
Some bonds rotate at higher temperatures - in natural Fatty Acids nearly all double bonds are in CIS
rotation
Trans-fatty acids present in some foods as by product of saturation of fatty acids in hydrogenation of
natural oils margarine. Unhealthy diabetes mellitus and cardiovascular disease
CIS double bond places a KINK in linear structure interfereing with close packaging of chain. Ie lower
melting point.
Melting points increase with chain length and decrease with unsaturation
Membrane lipids which must be fluid at all times are more unsaturated than storage lipids
Lipids in tissues that are exposed to cooling are more unsaturated eg hibernators

Triglycerides main storage form for Fatty Acids. (esters of glycerol and FAs)ENERGY STORE
Carbons 1 and 3 in glycerol are not identical eg. Enzymes distinguish glycerol is always phosphorylated
on sn-3 by glycerol kinase and gives glycerol-3-phosphate not glycerol -1-phosphate
In humans triglycerides are formed in adipose tissue (solid form) and are degraded to glycerol and F.As
and released into plasma for metablolism.
Saponification ester bond hydrolyzed by a strong base NaOH forming glycerol and F.As. one of the
products (sodium salt of fatty acid) is SOAP.
Phospholipids main lipid constituents of membranes. They are derivatives of phosphatidic acid
phosphate is esterified with OH of an alcohol. Phosphate acts as a bridging diester to link to a polar
nirtrogenous compound most commonly choline, ethanolamine or serine. Lecithin (phosphotidylcholine)
Phosphatidylcholines (lecithins) in Cell membranes large proportion of bodys choline.
Choline is important in nervous transmission Ach and as a store of labile methyl groups

Complex lipids:
Glycerophospholipids and sphingolipids
Found either embedded in membranes or in circulating lipoproteins
Sphingolipids almost exclusively on Plasma membranes and carry carbs facing exteriorly recognition
Glycerophospholipids are saponifiable (except plasmalogens)
Sphingolipids contain no alkali-labile ester bonds.

















Cell membrane
Highly fluid dynamic structures
Asymmetric lipid bilayer; distinct inner and outer surfaces
Electrically polarized ( negative inside)
Plasma membranes:
closed compartments that define cell bodies
Selective Permeability & act as a barrier between in and out
^^Specific proteins: Transporters and Ion channels
Exchanges material by exocytosis and endocytosis
Gap junctions adjacent cells exchange materials
Imp: Cell-Cell Interactions and Transmemrane signaling
Form specialized components within the cell shape organelles
Membranes internalize and compartmentalize body water
Body water: ICF and ECF (intra/extra-cellular)
Intracellular Fluid: 2/3 of body water
Provides specialized environment for the cell: make, store and utilize energy
Perform special functions repair itself to replicate
Rich in K+ ; Mg2+ ; and Phosphate is major anion
Higher Protein conc than ECF
Extracellular Fluid: 1/3 body water (plasma and interstitial components).
Delivery system: Nutrients Oxygen Ions and minerals Hormones
Removes: CO2 Wastes Toxic or detoxified materials
Rich in Na+ ; Ca2+ ; and Cl- major anion
Higher Glucose Conc than ICF

Membranes develop PUMPS to maintain internal microenvironment
Membranes are sheetlike structures noncovalent assemblies

Phospholipids: 2 classes found in membranes: 1
st
: phosphoglycerides
2
nd
: composed of sphingomyelin
Phosphoglycerides are more common
Consists of a Glycerol backbone to which are attached 2 Fatty acids and a phosphorylated alcohol
The fatty acids: usually 16-18 Carbons; unbranched and saturated or unsaturated with one or more CIS
double bonds
Phospholipids Composed of sphingolmyelin: contain sphingosine backbone and F.A attached by amide
linkage to amino grp of sphingosine forming CERAMIDE.
Primary hydroxyl group of sphingosine is esterified to phosphorylcholine forming sphingomyelin.
Imp in myelin sheaths

Glycosphingolipids (GSLs)
Sugar-containing lipids built on a backbone of ceramide: include galactosyl- and glucosyl- ceramide and
gangliosides.
Sterols
Most common is cholesterol in plasma membranes but sometimes in mitochondria, Golgi and nuclear
membranes. Intercalates among the phospholipids with OH grp at surface affects the fluidity
All membrane lipids can be separate by Column, thin-layer and gas-liquid chromatography and
structures established by mass spectrometry.
MEMBRANE LIPIDS ARE AMPHIPATHIC
Contain both hydrophobic and hydrophilic regions. Membrane becomes more fluid with more
unsaturated FAs as more kinks and less tightly packed
DETERGENTS = amphipathic molecules similar to phospholipids. Some used to solubilize proteins.
Hydrophobic part of detergent binds to hydrophobic part of proteins and displaces the bound lipids.
Polar end of the detergent then brings protein into solution as detergent-protein complexes.
MEMBRANES FORM BILAYERS Phospholipids arrange into micelles in water with hydrophobic regions
shielded by the polar heads. However in membrnes they form LIPID BILAYERS not micelles. Sheet with
hydrophobic regions shielded from surrounding aqueous environment. This membrane is impermeable
to water soluble molecules as they do not pass through insoluble hydrophobic core.
Lipid bilayers formed by self-assembly hydrophobic interactions

Membrane proteins maintain transmembrane concentrations:
Channels(for ions and small molecules) and
Transporters (for larger molecules)
Membrane phospholipids act as solvent for proteins, allowing them to function.
The alpha helical structure of proteins minimizes hydrophilic character of peptide bonds. Proteins are
therefore amphipathic with hydrophilic regions protruding of the membrane. Some proteins are
anchored to membrane by covalent linkages to certain lipids: Palmitate and myristate are F.As involved.
Most membrane proteins can be separated from each other using SDS-PAGE (sodium dodecylsulfate
polyacrylamide gel electrophoresis) technique separating proteins according to molecular mass. SDS is
a powerful detergent disrupting protein-lipid interactions and solubilizes membrane proteins. Also
disrupts protein-protein interactions, unfolding them.
MEMBRANES = Dynamic Structures
Lipids and proteins in membranes undergo turnover.
Lipids and some proteins exhibit lateral diffusion in their membrane (some proteins do not as
they are attached to actin cytoskeleton)
Transverse movements of lipids is extremely slow
MEMBRANES = Asymmetric
Inside different to outside due to unique orientations of proteins and carbohydrates are attached to the
outer proteins
Regional heterogeneities - macroscopically: villous membranes of mucosal cells
Microscopically: gap junctions, tight junctions and synapses smaller local asymmetries
Inside/outside asymmetry of phospholipids: choline-containing phospholipids are in outer membrane
aminophospholipids are more often on inner layer.
Phospholipids therefore have limited slow transverse flip flop movement.
Translocases FLIPPASES transfer vertain phospholipids(phosphotidylcholine) from inner to outer
leaflet
Further asymmetry: in GSLs and glycoproteins the suger parts protrude outwards absent from inner
INTEGRAL AND PERIPHERAL PROTEINS
Most are integral
interact extensively with phospholipids and
require use of detergents for solubilization
They span entire bilayer.
And are usually globular and amphipathic (two hydrophilic heads with a hydrophobic region)
Peripheral proteins: -
Do not interact with hydrophobic cores of bilayer
Do not require use of detergent for release
Bound to hydrophilic regions of integral proteins and phospholipid
Can be released with salt solutions of high ionic strength eg.ANKYRIN peripheral protein
bound to inner aspect of integral protein band 3 of RBC memb.
SPECTRIN cytoskeletal structure within RBC and is bound to ankyrin to maintain biconcave
shape of erythrocyte.
ARTIFICIAL MEMBRANE SYSTEMS mixtures of phospholipids which can be treated to form LIPOSOMES
FLUID MOSAIC MODEL OF MEMBRANE STRUCTURE
Proposed by Singer and Nicholson in 1972 icebergs floating in a sea
Phospholipids can move in the plane of the membrane lateral diffusion
Fluidity depends on the lipid composition of the membrane. As fluidity increases so does its permeability
to water and other hydrophilic molecules and lateral mobility of integral proteins increases.
Eg Insulin receptor: as conc of unsaturated fatty acids in the membrane increases fluidity increases and
the receptor binds to more insulin
SPECIALIZED STRUCTURE iN PLASMA MEMBRANES:
Lipid rafts: specialized areas of outer membrane layer richer in cholesterol sphingolipids and
certain proteins. IMP for Signal transduction
Caveolae may derive from lipid rafts. Contain CAVEOLIN-1 protein. Appear as flask-like
indentations of membrane. Proteins detected in caveolae: folate receptor, the endothelial
nitric oxide synthase eNOS,
and components of signal transduction eg insulin receptor and some G proteins.
Tight junctions below apical surfaces of epithelial cells and prevent diffusion of
macromolecules between cells. Composed of: occluding,claudins,junctional adhesion
molecules.
Desmosomes, adherens junctions and microvilli not described here
Hormones can regulate facilitated diffusion by changing the no. of transporters available
Insulin increases glucose transport in fat and muscle by recruiting transporters from an
intracellular reservoir. Also AA transport in liver and other tissues.
Glucocorticoid hormone enhances transport of AAs into liver for gluconeogenesis
Growth hormone increases AA transport in all cells
Estrogen increases AA transport in uterus
Most AA transporters are Na+ symporters

















Fat Soluble Vitamins:
Vitamin A
^^Generic term for retinal, retinol and retinoic acid Retinoids
The provitamin of vitamin A is -carotene which is water-soluble.
-carotene is converted to all-trans retinal by action of -carotene dioxygenase in small intestine
Vitamin A is stored in liver in the form of retinol and retinyl esters (retinol palmitate) bound to cystolic
retinol binding proteins (CRBP). Retinol is excreted from the liver bound to serum retinol-binding protein
(RBP).
Retinoic acid is thought to be transported to all cells bound to albumin or a specific retinoic acid binding
protein (RABP). Retinol is taken into cells by a membrane receptor.
Retinoic acid is a signaling molecule which interacts wth ligand-activated transcription factors, nuclear
retinoid receptors. The retinoic acid receptors (RAR) bind all-trans and 9-cis retinoic acid
while rexinoid receptors (RXR) bind the 9-cis isomer only. These receptors can form heterodimers.
RXR receptors can also interact with other nuclear receptors eg vitamin D3, thyroid hormones or
peroxisome proliferator-activated receptors(PPARs). Retinoic acid also has a role in growth and
development of CNS.
Dark green and yellow vegetables are good sources of -carotene.
Conversion of carotenoids to vitamin A is rarely 100% efficient and
Liver stores a 1 year supply of vitamin A.
Liver egg yolk and milk are good sources of preformed vitamin A.