Lipids

Lipids are hydrophobic, nonpolar molecules.

• They are soluble in nonpolar solvent.

• They are insoluble in polar solvents, such as water

They are isolated from the other biological molecules by extracting them with nonpolar solvents.

Categories based on biochemical function:

•  Energy-storage lipids ((triacylglycerol)

• Protective-coating lipids (biological waxes)

• Membrane Lipids (phospholipids, spingolipids, cholesterol)

• Emulsification lipids (bile acids)

• Messenger lipids (steroid hormones and  eicosanoids)

Categories based on saponification

·        Saponifiable lipids – converted to smaller molecules  through hydrolysis

o   Ex:  Triacylglycerols, glycerophospholipids, spingophospholipids, spingoglycolipids, biological waxes

·        Nonsaponifiable lipids –cannot be broken up into smaller units since they do not react with water

o   Ex: Cholesterol, bile acids, Steroid hormones, eicosanoids

Fatty Acids

Fatty Acids-  naturally occuring monocarboxylic acids

Fatty acids contain a carboxylic acid group

• They have a polar end in solution

However, they also contain a long hydrocarbon tail

• Which overall, makes them nonpolar.

Fatty acids typically contain between 12 and 20 carbons

• The number is usually always even

• The nonpolar tails interact with London forces.

• Rarely found free in nature but as part of lipids

Fatty Acids

·        The shortest descriptions (shorthand system/notation)of fatty acids include only the number of carbon atoms and double bonds in them (e.g. C18:0 or 18:0). 

o   C18:0 means that the carbon chain of the fatty acid consists of 18 carbon atoms and there are no (zero) double bonds in it, whereas C18:1 describes an 18-carbon chain with one double bond in it. 

·        Each double bond can be either in a cis- or trans- conformation and in a different position with respect to the ends of the fatty acid, therefore, not all C18:1s, for example, are identical. 

o   If there is one or more double bonds in the fatty acid, it is no longer considered saturated, rather it makes it mono- or polyunsaturated.

Unsaturated fatty acids are of similar form, except that one or more alkenyl functional groups exist along the chain, with each alkene substituting a singly- bonded " -CH2-CH2-" part of the chain with a doubly-bonded "-CH=CH-" portion (that is, a carbon double bonded to another carbon).

The two next carbon atoms in the chain that are bound to either side of the double bond can occur in a cis or trans configuration.

cis/trans-Delta-x or cis/trans-Δ^x: The double bond is located on the xth carbon-carbon bond, counting from the carboxyl terminus. The cis or trans notation indicates whether the molecule is arranged in a cis or trans conformation.

The cis or trans notation indicates whether the molecule is arranged in a cis or trans conformation.

Saturated fatty acids do not contain any double bonds or other functional groups along the chain.

·        The term "saturated" refers to H, in that all carbons (apart from the carboxylic acid [-COOH] group) contain as many hydrogens as possible. 

·        In other words, the omega (ω) end contains 3 hydrogens (CH₃-) and each carbon within the chain contains 2 hydrogen.

·        A cis configuration means that the two  connected carbons (on the C=C bond)  are on the same side of the double bond.

·        The rigidity of the double bond freezes its conformation and, in the case of the cis isomer, causes the chain to bend and restricts the conformational freedom of the fatty acid.

Omega-x or ω-x : A double bond is located on the xth carbon-carbon bond, counting from the ω, (methyl carbon) end of the chain. Sometimes, the symbol ω is substituted with a lowercase letter n, making it n-6 or n-3.

Melting points for saturated fatty acids:

The more double bonds the chain has in the cis configuration, the less flexibility it has. When a chain has many cis bonds, it becomes quite curved in its most accessible conformations. For example, oleic acid, with one double bond, has a "kink" in it, 

while linoleic acid, with two double bonds, has a more pronounced bend.

 Linolenic acid, with three double bonds, favors a hooked shape. 

The effect of this is that in restricted environments, such as when fatty acids are part of a phospholipid in a lipid bilayer, or triglycerides in lipid droplets, cis bonds limit the ability of fatty acids to be closely packed and therefore could affect the melting temperature of the membrane or of the fat.

Normally the double bonds are cis

• This lowers the melting points for fatty acids containing double bonds. (London forces)

A trans configuration, by contrast, means that the next two carbon atoms are bound to opposite sides of the double bond. As a result, they don't cause the chain to bend much, and their shape is similar to straight saturated fatty acids.

As acids, the carboxylic acid group in fatty acids can react with a base to produce a carboxylate ion

• By donating its proton (H⁺) to the base the fatty acid becomes negatively charged.

In most naturally occurring unsaturated fatty acids, each double bond has 3n carbon atoms after it, for some n, and all are cis bonds. 

Most fatty acids in the transconfiguration (trans fats) are not found in nature and are the result of human processing (eg, hydrogenation).

Trans Fats and the Body

• The human body is capable of synthesizing most fatty acids from 

               carbohydrates or other fatty acids.

• Humans do not synthesize sufficient amounts of fatty acids that 

               have more than one double bond.

• More than one double bond fatty acids are called essential fatty acids and they must be provided by the diet.  

Omega-n acids

n: the position of the first double bond

Linoleic acid is called an omega-6 acid, because of the position of the first C=C in the nonpolar chain.

Linolenic acid is called an omega-3 acid, because of the position of the first C=C in the nonpolar chain.

The differences in geometry between the various types of unsaturated fatty acids, as well as between saturated and unsaturated fatty acids, play an important role is biological processes, and in the construction of biological structures (such as cell membranes).

ENERGY STORAGE LIPIDS: TRIACYLGLYCEROLS

Triacylglycerols are:

• Fats and oils (are stored in the body).

• Triesters of glycerol.

• Produced by Fischer esterification.

• Formed when the hydroxyl groups of glycerol react with the carboxyl groups of fatty acids.

Produced by esterification of glycerol (a trihydroxyl alcohol).

Simple triacylglycerols have three identical fatty acid side chains.

Mixed triacylglycerols have two or three different fatty acids.

Triglycerides

·        Saturated triacylglycerols contain only saturated fatty acids.

·        Monounsaturated triacylglycerols have 1 C=C  bond.

·        Polyunsaturated triacylglycerols have many C=C bonds.

·        Increasing the number of double bonds in the fatty acid chain decreases the melting point of the triacylglycerol.

Fat: is a triacylglycerol that is solid at room temperature.

Made by more saturated fatty acids (Saturated triacylglycerols). Meat, milk, butter and cheese (animal sources).

Oil: is a triacylglycerol that is liquid at room temperature.

Made by more unsaturated fatty acids (Unsaturated triacylglycerols). Corn, cotton seed, safflower and sunflower (plant sources).

Both are colorless, odorless, and tasteless.

Fat & Health

·        Fats are used to build cell membranes, insulate the body, and store energy for later use.

·        It is recommended that no more than 20-35% of a person’s caloric intake should come from lipids.

·        A high intake of saturated triacylglycerols is linked to heart disease.

·        Saturated fats stimulate cholesterol synthesis in the liver, which can lead to cholesterol plaques building up inside arteries.

·        The result is high blood pressure, heart attack, and even stroke.

·        Unlike other vegetable oils, oils from palm and coconut trees are very high in saturated fats.

·        Unsaturated triacylglycerols (omega-3 fatty acids from fish) lower the risk of heart disease by decreasing the level of cholesterol in the blood.

·        However, if the double bond of the unsaturated triacylglycerol is trans, the beneficial effect is lost.

·        Trans fats, which are primarily synthesized instead of naturally occurring, act like saturated fats and increase the cholesterol levels in the blood.

•  Hydrogen adds to the double bonds of unsaturated fats (using transition metal catalyst such as Ni).

•  Melting point is increased.

·        Liquid oils are converted to semi-solid fats.

Reactions of Triglycerides

Hydrogentation

Hydrolysis

Triacylglycerols are hydrolysis (split by water) in the presence of strong acid or lipase (digestive enzyme). 

Metabolism of tricaylglycerols

·        Humans store energy as triacylglycerols in adipose cells below the surface of the skin, in the breast area, and surrounding internal organs.

·        The number of adipose cells is constant; weight gained or lost causes them to swell or shrink, but not decrease or increase in number.

·        To metabolize triacylglycerols for energy, the esters are hydrolyzed by enzymes called lipases.

·        Complete metabolism of a triacylglycerol yields CO₂, H₂O, and a great deal of energy. 

Saponification (Basic Hydrolysis)

·        Is the process of forming “soaps”  (salts of fatty acids).

·        Is the reaction of a fat with a strong base (NaOH).

·        Splits triacylglycerols into glycerol and the salts of fatty acids. 

·        With KOH or the oils that are polyunsaturated gives softer soaps (liquid soaps).

·        Soaps are typically made from lard (from hogs), tallow (from cows or sheep), coconut oil, or palm oil.

·        All soaps work in the same way, but have different properties depending on the lipid source, length of C chain, and degree of unsaturation.

Soaps

·        Hydrophobic part: nonpolar

·        Hydrophilic part: polar (remains in contact with environment)

When soap is mixed with dirt (grease, oil, and …), soap micelles “dissolve” these nonpolar, water-insoluble molecules.

Oxidation

Oxidation breaks double bonds, producing aldehyde or carboxylic acid products. (Oil turning rancid)

Protective-coating lipids: Biological Waxes

Wax is an ester of saturated fatty acid and long chain alcohol.

Waxes

For example, shown below is the formation of spermaceti wax, isolated from the heads of sperm whales.

Because of their long nonpolar C chains, waxes are very hydrophobic.

They form protective coatings:

•  In plants, they help prevent loss of water and damage from pests.

•  In humans and animals, provide waterproof coating on skin and fur.

Hydrolysis reaction: like other esters, waxes are hydrolyzed.

Membrane lipids: Phospholipids and Glycolipids

Phospholipids and Glycolipids are the stuff that biological membranes are made of.

·        Like the soaps, these molecules are highly aphipathic, and when mixed with water spontaneously form membranes that are described as lipid bilayers.

There are two types of phospholipids

Glycerophospholipids

·        The Glycerophospholipids have a structure similar to triglycerides, with one of the fatty acids replaced with a phosphate.

·        There is usually an additional alcohol attached to the other side of the phosphate

“Phosphotidyl-” refers to everything but the X

Phospholipids

• Phospholipids are used commercially as emulsifying agents.

  • An emulsifying agent stabilizes an emulsion.

  • An emulsion is a colloidal suspension of one liquid in another.

  • An example is mayonnaise, which is a colloidal suspension of oil and water.

• Lecithin, which is another name for the phospholipid phosphotidylcholine, is used as an emulsifying agent in mayonnaise and other prepared foods.

Sphingophospholipids

• The sphingolipids function similarly to the glycerophospholipids, but structurally they are different.

• There is not glycerol core

• The glycerol and one of the fatty acids found in glycerophospholipids is replaced with a molecule called sphingosine.

• The sphingolipids are found in the myelin membranes that insulate the nerve cells.

• Some sphingolipids use sugars for the alcohol portion of the molecule

• These are called glycolipids.

Cell Membrane

    Fluid mosaic model

Semipermeable: selected nutrients can enter and waste products can leave.

·        Peripheral proteins are embedded within the membrane and extend outward on one side only.

·        Integral proteins extend through the entire bilayer.

·        Sometimes carbohydrates are attached to the exterior of the cell forming glycolipids and glycoproteins.

Transport Across a Cell Membrane

·        Simple Diffusion: Small molecules like O₂ and CO₂ can diffuse through the cell membrane, traveling from higher to lower concentration.

·        Facilitated Transport: Larger polar molecules (glucose) and ions (Cl^- and HCO₃^-) travel through integral protein channels.

·        Active Transport: Other ions, Na⁺, K⁺, and Ca²⁺, move against the concentration gradient; this required energy input.

Steroids

Steroids have:

·        A steroid nucleus which is 4 carbon rings.

·        Attached groups that make the different types of compounds.

·        No fatty acids.

Cholesterol

• Is the most abundant steroid in the body.

• Insoluble in water (need a water soluble carrier).

• Has methyl CH₃- groups, alkyl chain, and -OH attached to the steroid nucleus.

 Cholesterol

• Is obtained from meats, milk, and eggs. 

• Is synthesized in the liver from fats, carbohydrates and proteins.

• Is needed for cell membranes, brain and nerve tissue, steroid hormones, and Vitamin D.

• Clogs arteries when high levels form plaque (because it is insoluble in blood).

• No cholesterol in vegetable and plants.

Lipoproteins

Water-soluble form of lipids (soluble in blood) 

·        Spherical particles

·        Polar surface and nonpolar inner

Transporting lipids through the bloodstream to tissues where they are stored, Used for energy, or to make hormones.

Lipoproteins

·        VLDL: very-low-density lipoprotein (Triglycerides and Cholesterol)

·        LDL: low-density lipoprotein (bad Cholesterol) (Cholesterol)

·        HDL: high-density lipoprotein (good Cholesterol) (Cholesterol)

·        Chylomicrons: Triglycerides and Cholesterol

Recommended levels are: HDL > 40 mg/dL, LDL < 100 mg/dL, total serum cholesterol < 200 mg/dL.

Messenger Lipids

Steroid Hormones

·        A hormone is a molecule that is synthesized in one part of an organism, which then elicits a response at a different site.

Two types of steroids hormones:

1.      Sex hormones

Estrogens & progestins in females

The estrogens estradiol and estrone control development of secondary sex characteristics, regulate the menstrual cycle, and are made in the ovaries.

The progestin progesterone is called the “pregnancy hormone”; it is responsible for the preparation of the uterus for implantation of a fertilized egg.

Androgens in males

Testosterone and Androsterone are androgens made in the testes.

·        They control the development of secondary sex characteristics in males.

2.      Adrenal Cortical Steroids

·        Synthetic androgen analogues, called anabolic steroids, promote muscle growth.

·        They have the same effect as testosterone, but are more stable, so they are not metabolized as quickly.

·        They have come to be used by athletes and body builders, but are not permitted in competitive sports.

·        Prolonged use of anabolic steroids can cause physical and psychological problems.

Examples of anabolic steroids

Adrenal Cortical Steroids

·        Aldosterone regulates blood pressure and volume by controlling the concentration of Na⁺ and K⁺ in body fluids.

·        Cortisone and cortisol serve as anti-inflammatory agents, which also regulate carbohydrate metabolism.

Cortisone

Cortisone are used to suppress organ rejection after transplant surgery and to treat many allergic and autoimmune disorders.

·        Prolonged use of these steroids can have undesired side effects, including bone loss and high blood pressure.

·        Prednisone, a synthetic alternative, has similar anti-inflammatory properties but can be taken orally.

Eicosanoids

Prostaglandins and Leukotrienes are two types of eicosanoids (20 C atoms derived from the fatty acids).

·        All eicosanoids are very potent compounds, which are not stored in cells, but rather synthesized in response to external stimulus. 

·        Unlike hormones they are local mediators, performing their function in the environment in which they are synthesized.

Prostaglandins

Prostaglandins are carboxylic acids that contain a five-membered ring and have a wide range of biological activities.

Prostaglandins are responsible for inflammation.

·        Aspirin and ibuprofen relieve pain and inflammation by blocking the synthesis of these molecules.

·        Prostaglandins also decrease gastric secretions, inhibit blood platelet aggregation, stimulate uterine contractions, and relax smooth muscles.

·        There are two different cylcooxygenase enzymes responsible for prostaglandin synthesis called COX-1 and COX-2.

Prostaglandins

·        COX-1 is involved in the usual production of prostaglandins.

·        COX-2 is responsible for additional prostaglandins in inflammatory diseases like arthritis.

·        Nonsteroidal anti-inflammatory drugs (NSAIDs) like aspirin and ibuprofen inactivate both COX-1 and -2, but increase risk for stomach ulcer formation.

·        Drugs sold as Vioxx, Bextra, and Celebrex block only the COX-2 enzyme without affecting gastric secretions.

Leukotrienes

·        Asthma is characterized by chronic inflammation, so inhaled steroids to reduce this inflammation are commonly used.

·        Leukotrienes are molecules that contribute to the asthmatic response by constricting smooth muscle of the lung.

·        New asthma drugs act by blocking the synthesis of leukotriene C₄, which treat the disease instead of just the inflammation symptoms.

Emulsification Lipids: Bile acids

Bile acid – a cholesterol derivative  that functions as a lipid-emulsifying agent in the aqueous environment  of the digestive track

·        Bile is a dark green to yellowish brown fluid, produced by the liver of most vertebrates, that aids the digestion of lipids in the small intestine. In humans, bile is produced continuously by the liver

Primary bile acids are those synthesized by the liver. Secondary bile acids result from bacterial actions in the colon.