Lipids  Protective-coating Lipids (biological waxes)

 soluble in organic solvents but not in water Fatty acids

 Lipos (fat)  Long, unbranched carbon chains with carboxylic group at one end
 can be extracted by nonpolar solvents (ether and chloroform)  Classifications:
 Refers to a collection of organic molecules of varying chemical composition  Length of the Carbon Chain
 Are grouped together on the basis of their solubility in nonpolar solvents o Long-chain, medium-chain, short-chain
 Not polymers  Degree of Unsaturation
o Saturated, Unsaturated (Mono, Poly)
Biologic Functions:  Location of Double Bonds
o Omega-3 Fatty Acid, Omega-6 Fatty Acid (6 carbons away from the methyl end or
 Energy Source CH3 )
o When oxidized, each gram of fat releases 9 kcal of energy, or more than twice the energy
released by oxidation of a gram of carbohydrate a. Short-Chain Fatty Acids
 Energy Storage  Less than 6 carbons (penthanoic / valeric)
o In the form of triglycerides (TAG) in adipocytes  From the indigestible food sources (colon)
 Cell Membrane Structural Components b. Medium-Chain Fatty Acids
o Phosphoglycerides, sphingolipids, cholesterol, and steroids make up the basic structure of all  8-10 carbons
cell membranes c. Long-Chain Fatty Acids
 More than 12 carbons (dodecanoic acid)
Q: Why do lipids release more energy than carbohydrates or protein?
- Because of its structure
Types of fatty acids
Acetyl – coenzyme A
- Product of lipids, carbohydrate and protein metabolism , substrate of ATP production a. Saturated Fatty acids (puno)
- Substrate for the citric acid cycle  Each C being “saturated” with H
 General Formula: CH3(CH2)nCOOH
 Hormones  Contains single bonds
o Steroid Hormones (nonpolar in nature)
 Vitamin Absorption Examples:
o Dietary fat serves as a carrier of the lipid – soluble vitamins (ADEK)
o Non polar they have difficulty to be ingested or to be absorbed in the intestinal cells  Lauric Acid
 Protection
o fats as shock absorber (cushions)
 Insulation
o subcutaneous fat (natural blanket from cold weather)
 Myristic acid (14; added to proteins – myristilation)
Classification:

 Energy Storage Lipids (triacylglycerols)

 Membrane Lipids (phospholipids, sphingoglycolipids, and cholesterol)
 Emulsification Lipids (bile acids)
 Palmitic acid
 Messenger Lipids (steroid hormones and eicosanoids)
  Stearic acid

 are identified by position of the double bond nearest the methyl end (CH3) of the carbon
chain; this is described as an omega number;
 Capric acid
 If PUFA has first double bond 3 carbons away from the methyl end = omega 3 FA
 6 carbons from methyl end = omega 6 FA

b. Unsaturated Fatty acids

 Composed of at least one carbon-to-carbon double bond
Isomers (same molecular formula but different
 Almost are in the cis (Latin – on the same side) configuration

c. Monounsaturated
 Composed of one carbon-to-carbon double bond

Example:

 Oleic acid – Monounsaturated fatty acid

d. Polyunsaturated Fatty acids

 Composed of more than one carbon-to-carbon double bond

structural arrangement) of fatty acids

a. Cis
  More prevalent
 Hydrogen at the same side of the double bond  A neutral glyceride – adipocyte
 “kink” at the double bond site  Triester: glycerol + fatty acids
 Naturally occurring  Forms:
 Simple
b. Trans (opposite side of)  Mixed
 No “kink”(bends) at the double bond site  Triglyceride
 Hydrogen on the opposite side of the double bond
 Occur in partially hydrogenated food a. Neutral glycerides
 Produced after the esterification (joining together through dehydration of glycerol and fatty
Physical properties of fatty acids acid) of glycerol with a fatty acid
 Esterification may occur at one, two, or all three positions, producing:
a. Saturated
 Monoglycerides – 1 fatty acid added to the glycerol backbone
 Fit closely together allowing dispersion forces between the carbon chains  Diglycerides
 High melting point  Triglycerides – most important and main storage form of lipids in man (adipocytes)
 Solid at room temperature

b. Unsaturated
 Cannot stack closely due to double bond
 Fewer interactions between carbon chain
 Liquid at room temperature

Fats and oils

 Naturally occurring mixtures of triacylglycerols
 How are they different?
 The type of fatty acid present on its triglyceride molecule

Dietary Oil of Fat

c. Water solubility
 Longer chains are not totally soluble in water, shorter chain can be slightly soluble in water
(the degree of its non – polarity is also short)

d. Melting points
 Longer lengths has higher melting point and more double bonds has lower melting points

I. ENERGY STORAGE LIPIDS (triglycerides or triglycerol)

Are all fats bad? - More intake of omega 6 fatty acids the enzymes will be more focused in synthesizing the biologically
important omega 6 fatty acids
 Omega-3 - There will be less focus in synthesizing omega 3 fatty acids
o Eicosopentaenoic acid (EPA) – cardio protective effects and reduce inflammation
o Docosahexaenoic acid (DHA) – healthy eyesight, good brain function and prevent alzheimers Can the body synthesize omega 3 and 6?
disease - Provided that they have a modifiable pre-cursor containing the omega 3 or 6 double bond
o Alpha-linolenic acid (ALA) – some in small amounts can be converted to EPA and DHA
 flaxseed--most, canola (rapeseed), soybean, walnut, wheat germ
 body can make some EPA and DHA from ALA – if dili ma convert kay sources of
energy
 Omega-6
o corn, safflower, cottonseed, sesame, sunflower
o Linoleic acid – used to produce arachidonic acid (pre-cursor of chemical messengers in the
body

Essential fatty acids

 Linoleic acid
 Arachidonic acid (eicosanoids)
 Linolenic acid
 Eicosapentaenoic acid (EPA)
 Docosahexaenoic acid (DHA)

Chemical reactions of lipids

a. Esterification
o Fatty acids react with alcohols to form esters and water
Why is a ratio needed?
- The enzyme needed for the synthesis of omega fatty acids are the same
 d. Hydrogenation
o Used in the food industry to convert polyunsaturated vegetable oils into saturated solid
fats
o Can also occur in alkenes with a metal catalyst (platinum) to form an alkane

b. Hydrolysis (breaking down of ester with the aid of water to form fatty acids)
o Producing fatty acids from esters
o Opposite of esterification

Partial hydrogenation
 Carried out to add hydrogen to some, but not all, double bonds in polyunsaturated oils
 In this way liquid vegetable oils are converted into solid form (Crisco and margarine)

e. Oxidation
o Oxygen as oxidizing agent
o Production of aldehyde and carboxylic acid
c. Saponification
o “rancid” odor
o base-catalyzed hydrolysis of an ester
o Can be avoided
o the product of this reaction, an ionized salt, is a soap
by antioxidants
o have a long uncharged hydrocarbon tail and a negatively charged terminus (the
(by neutralizing
carboxylate terminus), they form micelles that dissolve oil and dirt particles
oxidizing agent or
o Hydrolysis of ester linkages
by reducing the
o Reaction with base
oxidizing agent)
o Pang break sa ester bond or the fatty acids are the bases: NaOH and KOH
o Product formed are fatty acid salts
o Product of saponification specifically 3 fatty acid salts will form a micelle; aggregate of
amphipathic molecules
o Micelle cleans up dirt by attracting the
non-polar dirts by its hydrophobic tail and
allows the dirt to be washed way
 Phosphatidylcholine (lecithin)
 An amphipathic molecule
 Similar to that of soap and detergent molecules
 Component of cell membranes
 Major phospholipid in pulmonary surfactant (surface active agents - which help reducing surface
tension of liquids; keep alveoli open for the entry of air)
 Found in egg yolks and soybeans
 As emulsifying agent in ice cream

Phosphatidylethanolamine (cephalin) – cell membrane of the platelets

 Serves as platform for the clotting factors to react to (cephalin will react or interact ang clotting factors
II. MEMBRANE LIPIDS to work for coagulation or hemostasis)
 Similar in general structure to lecithin
a. Phospholipids  Amine group bonded to the phosphoryl group is the only difference
 are group of lipids that are phosphate esters (are formed from the combination reaction of alcohol and b. Sphinglolipids
inorganic acid – H3PO4)  Are lipids that are not derived from glycerol
 components of phospholipid:  Amphipathic and structural components of cellular membranes
 fatty acid(s)  Derived from sphingosine (long chain, N-containing alcohol)
 phosphate group  Sphingomyelins
 platform molecule  Glycosphingolipids

Sphingomyelins
 located throughout the body, but are particularly important structural lipid components of nerve cell
membranes
 found in abundance in the myelin sheath (fast transmission from nerve cell to nerve cell)
 proper cerebral function and nerve transmission

Glycosphingolipids
 include the cerebrosides, sulfatides, and gangliosides
Phosphoglycerides  also built on a ceramide backbone structure, which is a fatty acid amide derivative of sphingosine
 Most abundant membrane lipids and derived from glycerol-3-phosphate
 Also known as glycerophospholipid Q: what makes glycosphingolipids different from sphingomyelins?
 At C-3 the phosphoryl group is joined to glycerol by a phosphoester bond - Instead of phosphate group and amino alcohol connected to the carbon in sphingosine, the connected
 Phosphatidate is carbohydrate group or a saccharide
o simplest phosphoglyceride contains a free phosphoryl group
Cerebrosides
 are characterized by the presence of a single monosaccharide head group
 Glucocerebroside – found in the membranes of macrophages
o Consists of ceramide bonded to the hexose glucose
 Galactocerebroside – found almost exclusively in the membranes of brain cells
o Consists of ceramide joined to the monosaccharide galactose
Sulfatides
  Sulfolipid  enzymes need to have a proper arrangement to its substrate for it to be activated / for it to
 Sulfated galactocerebroside act
 Important for the functionality of myelin sheaths  fat globules: if their arrangement is also disturbed or not proper, the enzyme lipase cannot
 Abundant at the terminal end of the myelin sheaths located at the nodes of ranvier and also important act upon the lipids
for signal transduction  what makes the emulsifying agent capable of degrading the globule into smaller fat units?
Through its amphipathicity (polar and non-polar ends)
Gangliosides
 firstly isolated from ganglion (collection of neuron cell bodies of the peripheral nervous system) cells
 cell membrane component that regulates signal transduction
 oligosaccharides to polysaccharides

c. Cholesterol
 steroid
 cannot be a source of energy
 buffer of membrane fluidity (bidirectional regulator of membrane fluidity; in high
temperatures cholesterol raises the melting point of the phospholipid bilayer; at  Difference between Cholic,
low temperature the cholesterol prevents the crystallization or clustering of 12 – deoxycholic and 7 –
phospholipids and prevents it to be too solid or too rigid of the cell membrane at deoxycholic acids is the
low temperatures) absence or presence of hydrogen group; “ic” carboxylic names; isopropyl end will be
 precursor substance for other biologically important compounds replaced by the carboxylic functional group of the carboxylic acid
 Can also exist in an esterified form called cholesteryl ester, with the hydroxyl group  bile salts are added with ions (sodium and potassium); more ionic – readily mixable with
conjugated by an ester bond to a fatty acid water
 No polar groups making them very hydrophobic  bile salts are excreted from the bile (mixture of bile salts, electrolytes and biliary cholesterol)
 Biliary cholesterol
d. Steroids - protective effect on liver sinuses against the toxic effects of bile salts
 an isoprenoid or terpenoid (pre cursor is isoprene – organic molecule composes of - rate is dependent on the cholesterol intake; more cholesterol intake, more
5 carbons with alternating double bonds; modified to produce various structures biliary cholesterol
 compounds whose precursor molecules are isoprene  During fasting, the liver will increase biliary cholesterol synthesis and excretion
 the plants produce isoprene to protect from thermal stresses and atinobacteria can  If there is more biliary cholesterol than bile salts, the excess cholesterol will accumulate or
utilize the isoprene as a fuel source crystallize that leads to gal stones (cholesterol that crystallized by increased live excretion of
biliary cholesterol)
III. EMULSIFICATION OF LIPIDS: BILE SALTS
• are amphipathic derivatives of cholesterol IV. MESSENGER LIPIDS: STEROID HORMONES
• synthesized in the liver and stored in the gallbladder  Hormones
 Cholate - Released in the body
 Chenodeoxycholate - Chemical messenger
 emulsifying agent – whose polar hydroxyl groups interact with water and whose hydrophobic - Biochemical substance produced by a ductless gland that has a messenger
regions bind to lipids (helps 2 immiscible liquids to be mixed macroscopically) function
 dietary lipids need to be emulsified in order to be absorbed - Activating some genes that are needed for certain protein protection
 fat globules are broken down  Steroid hormone
 too big to be acted upon by lipase (degradation of lipids) - Cholesterol-derivative hormone
 Sex hormones
 - Hormones which control reproduction and secondary sex characteristics - Increases blood pressure and heart rate
- Estrogens, Androgens, Progestins  Aldosterone
- A mineralocorticoid
- Regulates the levels of sodium and potassium in the body
 Progesterone
- Role in menstrual cycle, pregnancy and embryogenesis
 Estradiol
- Type of estrogen
- Menstrual cycle
- Increased level will result to the maturation of egg cells and its release from the
mature follicle (it houses the egg cells before they are released from the ovaries)
 Testosterone
- Male sex hormone
- Muscle mass development, bone growth and fat metabolism

V. MESSENGER LIPIDS: EICOSANOIDS

 Eicos (Greek) “20”
a. Adrenocorticoid Hormones
 Affect cells that are within its reach
- Produced by the adrenal gland
 Easily degraded by the body once produced
- A.k.a Supra renal gland (located above the kidney)
 20 C long fatty acid
- Adrenal cortex (where it synthesizes the steroid hormones)
- Mineralocorticoids – zona glomerulosa  Arachidonic acid
- Glucocorticoids – zona fasciculata - metabolic precursor of eicosanoids
- Sex hormones – zona reticularis  Potent but has short life
 Functions:
- Inflammation
- Pain and fever
- Blood pressure
- Blood clotting
- Reproductive functions
- Sleep/wake cycle
a. Prostaglandin
o Product of enzymatic modification of the arachidonic acid
o Affects the removal of the double bond in 8 – 9 and 11 – 12 carbon, 8 carbon is merged to
the 12-carbon making a pentane
o Classes of eicosanoids playing role in many different bodily functions: gastric juice
production, mucus production, initiation of fever and initiating inflammation and pain
o Causes blood vessels to dilate to increase blood flow in the area where the inflammation
 Cortisol and corticosterone are glucocorticoids (regulate or increase the pressure of glucose
occurs
in the bloodstream
o Tendency to attack the nerve endings present in that area and thus cause pain
 Cortisol
o Isolated from the prostate glands
- Chronic stress hormone
- Increased at times of stress
b. Leukotrienes
 o Presence of conjugated (the presence of double bonds are alternate) double bonds o Antiatherogenic (pick up excess or residue cholesterol present in the blood stream towards
o Trienes: refers to the 3 conjugated double bonds the liver for excretion)
o Leuko: produced by leukocytes or WBC 2. Apo B
o Released to initiate allergic responses o Is a large protein with MW 500 kD
o Principal protein on LDL, VLDL, and Chylomicrons
c. Thromboxane o Apo B-100 and Apo B-48

VI. PROTECTIVE – COATING LIPIDS: BIOLOGICAL WAXES a. Apo B-100

 Waxes - Is found on LDL and VLDL
- pliable, water-repelling substances used to protect and produce polished - Ligand for the LDL receptor
surfaces - Critical in the uptake of LDL in cells
a. Biological Waxes - Synthesized in the liver
- Monoester of a long-chain fatty acid and long chain alcohol b. Apo B-48
- Example: Lanolin - Exclusively found in chylomicrons
b. Mineral Waxes - Can also be found covalently linked to Apo A, a plasminogen (possibility to clot blood
- Mixture of long chain alkanes and trap fats to that clot) -like protein that is found in a proatherogenic
- Example: Paraffin - LPP particle called lipoprotein (a) [LP(a)]
LIPOPROTEIN - Synthesized in the intestines
- Classification (based on ultracentrifugation) 3. Apo E
 Chylomicrons [chylos] o Found in LDL, VLDL,and HDL
 Very-low-density LPP [VLDL] o Serves as a ligand for the LDL receptor and the chylomicron remnant receptor
 Low-density LPP [LDL] a. Apo E2
 High-density LPP [HDL] - Binds poorly to the cells
- The bigger the lipoprotein, the bigger its core (there are more lipids that are less dense than dense - Higher blood lipid levels
proteins) b. Apo E3
- Efficient ligand present in the cell
APOLIPOPROTEIN - Binds properly and greatly to cell
- Primarily located on the surface of lipoprotein particles c. Apo E4
- Functions: - Affect LPP metabolism because they differ in their ability to interact with the
 Help maintain the structural integrity of LPP LDL receptor
 Serve as ligands for cell receptors - Increase risk for Alzheimer’s disease
 As activators and inhibitors of the various enzymes that modify LPP particles
- Contain a structural motif called an amphipathic helix CHYLOMICRONS
- Are protein segments arranged in coils so that the hydrophobic amino acid residues interact with lipids - Contain apo B-48
- Helix containing hydrophilic amino acid faces away from the lipids and toward the aqueous - Account for the turbidity of postprandial plasma
environment  Readily float to the top of stored plasma and form a creamy layer
 chylous, turbid, milky, cloudy, lipemic plasma/serum
1. Apo A-I - largest lipoproteins and least dense of all lipoproteins
o Major protein on HDL  “the larger the lipoprotein, the larger the core, the larger the lipid content and the larger
o Frequently used as an index of the amount of the antiatherogenic HDL present in plasma lipid content, the less dense the particle is”
o Prevention of atherogenesis or formation of fat plaques in the arterial walls - Produced by the intestine, where they are packaged with absorbed dietary lipids
 Once enter the circulation, TAG and cholesteryl esters are hydrolyzed by lipase
  Are transformed into chylomicron remnant particles, which are taken up by remnant o Most active form in removing excess cholesterol from peripheral cells
receptors in the liver o Acquire additional lipid, cholesteryl esters, and TAG form a core region between the central
- Deliver dietary (exogenous) lipids to hepatic and peripheral cells lipid bilayer, which transforms into spherical HDL (predominant form in plasma)
b. Spherical HDL
How does chylomicrons deliver or deposit its triglyceride to the adipocytes and lipid liver cells? o HDL2
- Through lipoprotein lipase (enzyme present in the extracellular surfaces of the tissues) absorbed by - Larger in size and richer in lipid than HDL3
heparan sulfate - May be more efficient in delivering lipids to the liver
o HDL3
VERY LOW DENSITY LIPOPROTEIN (smaller than chylomicrons) - Smaller in size and less lipids
- Contain apo B-100, apo E, and apo C - Apo A1 and A2
- Produced by the liver Electrophoresis
- Rich in TAG like chylomicrons - Separation of molecules base on their charge and size
- Readily reflect light
- Account for most of the turbidity observed in fasting hyperlipidemic plasma specimens but do not form
a top, creamy layer
- Major carriers of endogenous (hepatic derived) triglycerides
- Transfer TAG from the liver to peripheral tissue
- Excess dietary intake of CHO, saturated fatty acids, and trans fatty acids enhances the hepatic synthesis
of TAG, thus, increases VLDL production

LOW DENSITY LIPOPROTEIN

- Contains apo B-100 and apo E
- More cholesterol-rich than other apo B- containing lipoproteins
- Primarily form as a consequence of the lipolysis of VLDL
- Readily taken up by cells via the LDL receptor
 Accounts for the reason that elevated LDL levels promote atherosclerosis
- Significantly smaller than VLDL and chylomicrons
 Can infiltrate into the extracellular space of the vessel wall, where it can be oxidized and
taken up by macrophages
 Become filled up with intracellular lipid drops and turn into foam cells
 an early precursor of atherosclerotic plaques

HIGH DENSITY LIPOPROTEIN

- Smallest and the most dense
- Synthesized by both the liver and intestine
- Can exist either as disk-shaped or as spherical-shaped particles
- Little to no lipid content
- Lipid content = cholesteryl esters

a. Discoidal HDL (Nascent HDL)

o Contains 2 molecules of apo A-I
o Represent newly secreted HDL