Biochemistry Lipids

Lipids are:
marginally insoluble in water but readily soluble in choroform or acetone
Two main groups:
Open-chain Amphipathic compounds
fatty acids
triacylglycerols
sphingolipids
phosphoacylglycerol
glycolipids
Cyclic
Sterols, steroid hormones , bile acids
Fatty Acids
carboxylic ggroup at polar end - hydrophilic
hydrocarbon chain at nonpolar tail - hydrophobic
amphipathic
Carboxyl can ionize under proper conditions
Fatty acids contain even numbered carbon atoms and are typically unbranched
rarely found free in nature, but form parts of commonly occurring lipids
** short hand for fatty acids number of carbons:number of double bonds- position of d.bond
Unsaturated & Saturated Fatty Acids
Unsaturated Fatty Acids
presence of carbon-carbon double bonds
stereochemistry in the double bonds are usually cis rather than trans
cis puts a kink in the longchain hydrocarbon tail
fatty acids do not normally have conjugated double bond system
have lower melting points compared to saturated
Plant oils have higher proportions of unsaturated fatty acids compared to animal fats
Hydrogenation process of adding hydrogen across the double bond of unsaturated
fatty acid to produce saturated counterparts
Essential Fatty Acids polyunsaturated fatty acids (Linolenic, Linoleic, arachidonic)

Triacylglycerols
Glycerol -contains three hydroxyl groups
Triacylglycerol / triglyceride
results when All three alcohol groups of glycerol forms ester bonds with fatty acids
do not occur as membrane components
accumulate in adipose tissue (fat cells)
provide means of storing fatty acids, particularly in animals
serves as concentrated stores of metabolic energy
Lipases enzymes capable of hydrolyzing ester linages of triglycerides
Saponification
Triacylglyceride + Base (NaOH or KOH) = Glycerol + Fatty acid salts
Hard soaps formed with addition of NaOH
Phosphoacylglycerols
One alcohol group esterified by a phosphoric acid rather than a carboxylic acid
important components of biological membranes
markedly amphipathic due to highly hydrophilic heads and non-polar hydrophobic tails
phosphoric acid is triprotic and can form more than one ester linkage
can form ester bonds to glycerol and to some other alcohol phosphatidyl ester
Phosphatidyl ester classification depends on the nature of the second alcohol esterified to
the phosphoric acid
Phosphatidyl ethanolamine (cephalin)
phosphatidyl serine
phsphatydyl choline
phosphatidyl inositol
phosphatidyl glycerol
diphosphatidyl glycerol
Waxes and Sphingolipids
Waxes complex mixtures of esters of long-chain carboxylic acids and long chain alcohols
serves as protective coating for both plants and animals
serves also as energy storage and water impermeable coating
long chain carboxylic acid + long chain alcohol
Sphingolipids do not contain glycerol instead they have sphingosine a long chain amino
alcohol
found in both plants and animals; abundant in the nervous systematic
sites of biological recognition
simplest class are ceramides one fatty acid linked to amino group of sphingosine via
amide bond
Sphingomyelins primary alcohol group of sphingosine esterified to phosphoric acid
amphipathic
occur in cell membranes in the nervous system

Glycolipids
carbohydrate bound to an alcohol grup of a lipid via glycosidic bond
often found as markers on cell membranes
play ar large role in tissue and organ specificity
ceramides parent components for glycolipids
Cerebrosides common sugars are glucose or galactose
found in nerve and brain cell membrane
glucocerebroside
galactocerebroside
Ganglioside are glycoplipids that contains more than three sugars

Steroids

fused-ring system of three six-membered rings + one five-membered ring

derivatives of cyclopentanoperhydrophenanthrene
sterols have an OH on carbon 3, and an aliphatic of 8C chain on carbon 17
includes hormones. Estrogen , androgen, progesterone, mineralcorticoids
Cholesterol squalenes cyclizes to form cholesterol
only hydrophilic group is the single OH
molecule is highly hydrophobic
cholesterol is widespread in biological membranes except in prokaryotic cell
presence of which in membranes can modify role of membrane-bound proteins
Precursor of other steroids and of vitamin D3
plays a role in atherosclerosis, a condition which lipid deposits block blood vessels

Biological Membranes
Natural Bilayers are Assymetric
do not only separate cells from external environment but also play a role in transport of
substances in and out of cells
facilitates cell cell communication
self sealing, selectively permeable to polar solutes, flexible
micelles are single layer of fatty acids
enzymes are found in membranes and depend on this environment for their function
Archaeal membranes
fatty acids joined to glycerol by ether linkage rather than ester
branched alkyl side chains
Phosphoglyceride are amphipathic molecules and are principal lipid components of
membranes
Difference between lipid bilayer and cell membrane
Cell membranes contain proteins as well as lipids
20% - 80% of cell membrane weight is protein
Glycolipids are also part of the lipid component of biological membranes
Steroids are present in eukaryotes
Cholesterol found in animal membranes
Phytosterol a lipid similar to cholesterol is found in plants
Bilayer arrangement held together by van der Waals and hydrophobic interaction
Polar heads contains charged groups
Interior contains Non-polar hydrocarbons consists of saturated and unsaturated chains of
fatty acids, and fused ring system of cholesterol
Bulkier molecules are outside, smaller molecules occur in the inenr layer

Effect of the Composition of Bilayer to properties

Arrangement of hydrocarbon can be ordered and rigid or disordered and fluid
Bilayer is curved, molecules of inner layer are more tightly packed
Bulkier molecules such as cerebrosides are found at the outer layer
Saturated Fatty acids linear arrangement, compact, contributes to rigidity
Unsaturated Fatty Acids presence of kink contributes to disorder, makes it more
fluid

Animal Membrane contains more saturated, cholesterol. More rigid than plants
Plant Membrane contains polyunsaturated fatty acids. More fluid than animals.
Plant sterols can act as natural cholesterol blockers
Prokaryotic Membrane - do not have appreciable amount of steroids thus making it
the most fluid
Heat Increases disorder , transition temperature is higher in rigid membranes
compared to less rigid membranes. Also increases fluidity and mobility
Cholesterol enhances order and rigidity, stabilizes the extended straight-chain
arrangement of saturated fatty acids via van der walls interaction.
Cholesterol can also increase fluidity by inserting between membrane lipids and
prevent close packing

Kinds of Membrane Proteins

Proteins can be attached to membrane in many ways
Proteins can be anchored to lipids via covalent bonds from cysteines or free amino groups
Myristoyl and Palmitoyl are common anchors, creates a Thioester linkage with Cys
Peripheral Proteins surface of the membrane
usually bound to the charged head groups of lipid bilayers by polar interactions,
electrostatic interaction, or both
can be removed by raising the ionic strength of the medium
Integral Proteins within the lipid bilayer
removal is much difficult. treatment with detergents or extensive sonication are usually
required. These treatments frequently denature proteins
Membrane proteins have a variety in function.
Transport Proteins help move substances in & out of the cell
Receptor Proteins plays a role in the transfer of extracellular signals, such as those
carried by hormones or neurotransmitters, into the cell
enzymes are tightly bound to membranes, such as those responsible for aerobic
oxidation, found in specific parts of mitochondrial membranes
Fluid Mosaic Model
allows lateral movement but not rotation through the membrane
components in the membrane exists side-by-side as separate entities
proteins float in the bilayer and can move along the plane of the membrane
Lipids are sorted into assemblages known as rafts
rafts become building blocks on which membrane specificity is based
Membrane Functions
three important functions take place in membranes
Transport - semipermeable barriers
transport through which is facilitated by the bilater or by membrane proteins
Uniport, Symport, Antiport
Catalysis - enzymatic action takes place on membrane
Receptor Property - proteins bind specific biologically important substances that trigger
biochemical responses in the cells
Transport
Passive Transport substance moves from higher concentration or lower concentration
follows the concentration gradient
does not expend energy
Simple Diffusion molecule moves directly through the membrane with no
interaction with other molecules
Oxygen, nitrogen, and carbon dioxide can pass via simple diffusion
Facilitated Diffusion makes use of carrier proteins without the use of energy
rate of transport gives a hyperbolic curve
Active Transport - substances move against the concentration gradient
requires energy ATP
presence of carrier proteins

Primary Active Transport

driven by ATP
Na-K pump, moving potassium ions into cell and simultaneously removing soidum
ions out
K is higher inside a cell than outside, Na higher outside the cell than inside
Process transports 3 Na ions out of the cell for every 2 K ions into the cell
Secondary Active Transport
example is the galactoside permease in bacteria
Driven by Hydrogen gradient
Membrane Receptors
interaction between receptor proteins and active substance is similar with with enzymesubstrate recognition
inhibition of action of the protein is possible by inhibitors
Receptors are usually oligomeric proteins
Many receptors are integral proteins
Cell signaling G proteins which requires hyddrolysis of GTP to operate
in cholera, G proteins are permanently activated.
Causes unregulated active transport of Na, leading to water and electrolyte loss, and
to diarrhea
an important type of receptor is for Low-density Lipoprotein, principal carrier of
cholesterol in bloodstream, consists of cholesterol, phosphoglycerides, and proteins
Excess of cholesterol inhibits synthesis of LDL receptors
IF There are Too little receptors for LDL , the level of cholesterol in blood stream increases
Gap Junctions
allow ions and small molecules to flow between communicating cells
Cell to cell channels
passageway of contiguous cells
made up of 12 molecules of connexin
Figures. Inhibition of LDL receptors & Gap Junction

Lipid Soluble Vitamins and their Functions

these vitamins are hydrophobic
Vitamin A
unsaturated hydrocarbon B-carotene is precursor of vitamin A
also known as Retinol
-carotene is converted to vitamin A whenever it is required
Vitamin A derivative plays a role in vision when bound to opsin
Vitamin A has an alcohol group that is enzymatically oxidized to an aldehyde , forming
Retinal.
Aldehyde group of Retinal forms imine,
Retinal + opsin = Rhodopsin
primary chemical event of vision in rod cells is absorption of light by rhodopsin
Vitamin D
structurally related compounds that are involved in calcium and phosphorus metabolism
regulation
Vitamin D3 - most abundant form in circulatory
formed from cholesterol by ultraviolet radiation from the sun
Increases synthesis of a Calcium binding protein, which increases dietary calcium in the
intestines
Deficiency of vitamin D can lead to rickets
Vitamin E
- tacopherol is the most active form of Vitamin E
Antioxidant good reducing agent, and reacts with oxidizing agents before they are able to
attack other biomolecules
protect important compounds including vitamin A from degradation
capable of removing, very reactive and dangerous substances known as free radicals
free radicals have at least one unpaired electron, accounting for its high degree of
reactivity
Vitamin K
important factor in blood-clotting process
Koagulation
long unsaturated hydrocarbon side consists of repeating isoprene units (terpenes are
hydrocarbons in multiples of five)
number of isoprene unites and degree of saturation makes a difference

Prostoglandins & Leukotrienes

Prostoglandins derived from fatty acids, first detected in seminal fluid
metabolic precursor of all prostaglandins is arachidonic acid
possibly useful in pharmaceutical industry due to the many physiological effects of
the compound
control of blood pressure, stimulation of smooth-muscle contraction, induction of
inflammation
Aspirin inhibits the synthesis prostaglandins in blood platelet
Prostaglandins are known to inhibit the aggregation of platelets
Leukotrienes derived also from arachidonic acid, and are found in leukocytes
constriction of smooth muscles, especially in lungs
Synthesis of leukotriene C causes Asthma Attacks
Drugs that inhibit Leukotriene C , are now used in the treatment of asthma