Lipids and Fatty Acids

Lipids Overview

• Lipids function in cellular energy storage, membrane composition, signaling, and other processes
• Fatty acids are water-insoluble hydrocarbons used for energy storage
• Membrane lipids have hydrophobic tails and polar head groups

Storage lipids

• They include Triacylglycerols
• They are used for energy storage

Fatty Acids

• Act as hydrocarbon derivatives
• Oxidation results in CO2 and H2O
• They are carboxylic acids with hydrocarbon tails ranging from 4 to 36 carbons (C4 to C36)
• Can be saturated or unsaturated
• Chain length and number of bonds separated by colon in nomenclature
• Carbon numbering starts at the carboxyl carbon
• Position of double bonds are indicated by Δ with superscript number
• Even numbers of carbon atoms in an unbranched chain of 12 to 24 carbons
• Monounsaturated fatty acids usually have a double bond between C-9 and C-10 (Δ9)
• Polyunsaturated fatty acids typically have double bonds at Δ12 and Δ15
• Double bonds in polyunsaturated fatty acids usually separated by a methylene group
• Double bonds are usually in the cis configuration
• Poorly soluble in water because of nonpolar hydrocarbon chain
• Increased chain length decreases solubility
• Carboxylic acid group is polar and ionized at neutral pH
• Saturated fatty acids have a waxy consistency at room temperature
• Unsaturated fatty acids are oily liquids at room temperature
• The extent of packing depends on the degree of saturation

Polyunsaturated Fatty Acids

• Contain more than one double bond in their backbone
• Omega-3 (ω-3) fatty acids have a double bond between C-3 and C-4 from the most distant carbon (ω)
• Omega-6 (ω-6) fatty acids have a double bond between C-6 and C-7 relative to ω

Triacylglycerols

• The simplest lipids, are constructed from fatty acids
• Composed of three fatty acids linked to a single glycerol via ester linkages
• Can be simple (one kind of fatty acid) or mixed (two or three different fatty acids)
• Hydrophobic and non-polar
• Vertebrates store them as lipid droplets in adipocytes (fat cells)
• Plants store them in seeds

Lipases

• Enzymes catalyze hydrolysis of stored triacylglycerols
• They release fatty acids for export to sites of use as fuel
• Adipocytes and germinating seeds contain these enzymes

Triacylglycerols vs Carbohydrates (Advantages and Disadvantages as Stored Fuels)

• Carbon atoms of fatty acids are more reduced, yielding more energy through oxidation
• Triacylglycerols are hydrophobic and unhydrated; organisms avoid carrying extra water weight
• Lipids are highly reduced, hydrophobic, and insoluble, which makes them difficult to transport
• Carbohydrates are hydrophilic, soluble, and quick energy sources
• Carbohydrates are hydrophilic and cannot be stored due to significant water attached

Additional Triacylglycerol Functions

• Seals, walruses, and penguins have ample padding providing insulation
• Hibernating animals, like bears, accumulate reserves for insulation and energy storage

Partial Hydrogenation

• Partial hydrogenation improves shelf life and stability
• Oxidative cleavage of double bonds in unsaturated fatty acids to aldehydes and carboxylic acids causes lipid-rich food to become rancid
• Process converting many cis double bonds to single bonds:
  • Improves shelf life and stability and melting temperature
  • Converts some cis double bonds to trans double bonds

Trans Fatty Acids

• Increased dietary intake of trans fatty acids is linked to cardiovascular disease
• Raise levels of triacylglycerols and LDL ("bad") cholesterol in the blood
• Lower levels of HDL ("good") cholesterol

Saponification

• Soap is prepared from fats

Biological Waxes

• Serve as energy stores and water repellents
• Esters of long-chain (C14 to C36) saturated and unsaturated fatty acids with long-chain (C16 to C30) alcohols
• Higher melting point than triacylglycerols
• Water-repellant properties
• Firm consistency

Structural Lipids in Membranes

• There are four types - phospholipids, glycolipids, sterols
• Biological membranes are double layers of lipids that act as barriers to polar molecules and ions

Membrane Lipids

• Amphipathic: one end of the molecule is hydrophobic and the other hydrophilic
• Hydrophobic regions associate with each other
• Hydrophilic regions associate with water

Phospholipids

• Regions composed of two fatty acids joined to glycerol or sphingosine

Glycolipids

• Contain a simple sugar or a complex oligosaccharide at the polar ends

Sterols

• Compounds characterized by a rigid system of four fused hydrocarbon rings

Glycerophospholipids (Phosphoglycerides)

• Membrane lipids with two fatty acids attached in ester linkage to the first and second carbons of glycerol
• Have a highly polar or charged group attached through phosphodiester linkage to the third carbon
• Can be of a wide variety
• Usually contain a C16 or C18 saturated fatty acid at the C-1 position
• Usually contains a C18 or C20 unsaturated fatty acid at the C-2 position

Sphingolipids

• Large class of membrane phospholipids and glycolipids
• Have a polar head group and two nonpolar tails, but contain no glycerol
• Contain one molecule of the long-chain amino alcohol sphingosine or one of its derivatives

Ceramides

• Structural parent of all sphingolipids
• C-1, C-2, and C-3 of sphingosine are structurally analogous to the three carbons of glycerol in glycerophospholipids
• When fatty acid is attached in amide linkage to the –NH2 on C-2
• Similar to diacylglycerol

Sphingomyelins

• Subclass of sphingolipids
• Contain phosphocholine or phosphoethanolamine as their polar head group

Gangliosides

• Have oligosaccharides as their polar head groups and 1+ residues of N-acetylneuraminic acid (Neu5Ac) at the termini
  • 1 sialic acid residue = GM (M for mono-) series
  • 2 sialic acid residues = GD (D for di-) series
  • 3 sialic acid residues = GT (T for tri-) series (and so on)

Sphingolipids at Cell Surfaces

• prominent in the plasma membranes of neurons

Human Blood Groups

• (O, A, B) are determined in part by the oligosaccharide head groups of glycosphingolipids

Sterols

• Structural lipids present in the membranes of most eukaryotic cells

Steroid Nucleus

• Consists of four fused rings
• It is almost planar
• Relatively rigid

Cholesterol

• Major sterol in animal tissues
• Amphipathic
• Polar head group and nonpolar hydrocarbon body
• Membrane constituent
• Similar to stigmasterol in plants and ergosterol in fungi

Steroid Hormones

• Regulate gene expression

Bile Acids

• Polar derivatives of cholesterol that emulsify dietary fats in the intestine
• Aid in making them more readily accessible to digestive lipases

Vitamin D

• Regulates calcium uptake

Lipids as Signals, Cofactors, and Pigments - Phosphatidylinositol

• Phosphatidylinositol (PI) and its phosphorylated derivatives regulate cell structure and metabolism

Phosphatidylinositol 4,5-Bisphosphate (PIP2)

• Found in the cytoplasmic face of plasma membranes
• Acts as a reservoir of messenger molecules released in response to extracellular signals
• Phospholipase C hydrolyzes PIP2 to IP3 and diacylglycerol (intracellular messengers)

Ceramide and Sphingomyelin

• Potent regulators of protein kinases
• Involved in the regulation of cell division, differentiation, migration, and programmed cell death

Eicosanoids

• Four major classes include prostaglandins, thromboxanes, and leukotrienes

Prostaglandins

• Class of eicosanoids with a five-carbon ring
• Stimulate contraction of the smooth muscle of the uterus
• Affect blood flow to specific organs, the wake-sleep cycle, and the responsiveness of certain tissues to hormones
• Elevate body temperature and cause inflammation and pain

Thromboxanes

• Act as Class of eicosanoids with a six-membered ring containing an ether
• Produced by platelets (also called thrombocytes)
• Act in the formation of blood clots and reduction of blood flow to the site of a clot

Leukotrienes

• Class of eicosanoids that contain three conjugated double bonds
• Leukotriene D4 induces contraction of the smooth muscle lining the airways to the lung
• Overproduction causes Anthemic attack

Vitamins

• Compounds essential to the health of humans and other vertebrates that cannot be synthesized

Fat-soluble Vitamins

• Are the groups A, D, E, and K

Vitamin D3 (Cholecalciferol)

• Formed in the skin from 7-dehydrocholesterol in a photochemical reaction driven by UV sunlight
• Is not biologically active until converted by enzymes in the liver and kidney to calcitriol

Vitamin D Deficiency

• Leads to defective bone formation and the disease rickets

Vitamin A1 (All-Trans-Retinol)

• Involved in processes of development, cell growth and differentiation, and vision
• Can be stored for some time in the body

Vitamin A Deficiency

• In pregnant women, leads to congenital malformations and growth retardation in the infant
• In adults, leads to dryness of skin, eyes, and mucous membranes, and night blindness

Golden Rice

• Is genetically engineered in beta-carotene

Vitamin E

• Collective name for a group of lipids called tocopherols

Tocopherols

• Hydrophobic compounds containing a substituted aromatic ring and a long isoprenoid side chain
• Associate with cell membranes, lipid deposits, and lipoproteins
• Acts as biological antioxidants

Vitamin E Deficiency

• Causes scaly skin, muscular weakness, and wasting, and sterility
• Very rare in humans
• Principal symptom: fragile erythrocytes

Vitamin K

• Contains an aromatic ring that undergoes a cycle of oxidation and reduction
• Forms active prothrombin, a blood plasma protein essential in blood clotting

Vitamin K Deficiency

• Results in slow blood clotting and increased risk of bleeding
• Extremely uncommon in humans