Chapter 10: Lipids

Fatty acids are water-insoluble hydrocarbons used for cellular energy storage.

10.1: Storage Lipids

Membrane lipids are composed of hydrophobic tails attached to polar head groups.

Fats and oils used as stored energy are derivatives of fatty acids

fatty acids are carboxylic acids with hydrocarbon tails ranging from 4 to 36 carbons long (C4 to C36)

oxidation of fatty acids to CO2 and H2O is highly exergonic

can be saturated or unsaturated

can be branched or unbranched

fatty acid nomenclature

for unbranched:

the chain length and number of double bonds, separated by a colon

numbering begins at the carboxyl carbon

positions of double bonds are indicated by delta and a superscript number

common patterns:

usually have even numbers of carbon atoms in an unbranched chain of 12 to 24 carbons

in monounsaturated fatty acids, the double bond is usually between C-9 and C-10 (delta9)

in polyunsaturated fatty acids...

the double bonds are usually delta12 and delta15

double bonds are usually separated by a methylene group

double bonds are usually in the cis conformation

polyunsaturated FAs: contain more than one double bond in their backbone

omega-3 fatty acids: double bond between C-3 and C-4 relative to the most distant (omega) carbon

omega-6 fatty acids: double bond between C-6 and C-7 relative to the most distant (omega) carbon

triacylglycerols: simplest lipids constructed from fatty acids

composed of three fatty acids, each in ester linkage with a single glycerol

can be simple (one kind of fatty acid) or mixed (two or three different fatty acids)

non-polar, hydrophobic

properties/interactions with environment:

have poor solubility in water due to the nonpolar hydrocarbon chain

decreased double bond number decreases solubility

carboxylic acid group is polar and ionized at neutral pH

fatty acid melting points:

increased chain length decreases solubility

at room temperature:

saturated fatty acids have a waxy consistency

unsaturated fatty acids are oily liquids

extent of packing depends on degree of saturation

provide stored energy and insulation

storage methods:

plants store triacylglycerols in the seeds

lipases: enzymes that catalyze the hydrolysis of stored triacylglycerols, releasing fatty acids for export to sites where they are required as fuel; found in adipocytes and germinating seeds

vertebrates store triacylglycerols as lipid droplets in adipocytes (fat cells)

advantages of using triacylglycerols as stored fuels

because carbon atoms of fatty acids are more reduced than those of sugars, oxidation of fatty acids yields more energy

because triacylglycerols are hydrophobic and unhydrated, the organism does not have to carry the extra weight of water hydration that is associated with stored polysaccharides

insulation:

seals, walruses, and other warm-blooded polar animlas are amply padded with triacylglycerols that provide insulation against low termperatures

hibernating animals accumulate huge fat reserves before hibernation, providing insulation and energy storage

partial hydrogenation of cooking oils improves their stability but creates fatty acids with harmful health effects

natural fats are complex mixtures of simple and mixed triacylglycerols

partial hydrogenation: process that converts many of the cis double bonds in the fatty acids to single bonds

reduces oxidative cleavage of double bonds in unsaturated fatty acids to aldehydes and carboxylic acids that causes lipid-rich food to become rancid

increases the melting temperature

converts some cis double bonds to trans double bonds

trans fatty acids

linked to a higher incidence of cardiovascular disease

raise the level of triacylglyceroles in the blood

raise the level of LDL (bad) cholesterol in the blood

lower the level of HDL (good) cholesterol

increase the body's inflammatory response

Waxes serve as energy stores and water repellents

biological waxes: esters of long-chain (C14-C36) saturated and unsaturated fatty acids with long-chain (C16-C30) alcohols

higher melting point than triacylglycerols

water-repellent properties

firm consistency

10.2 Structural Lipids in Membranes

biological membranes: double layer of lipids that acts as a barrier to polar molecules and ions

membrane lipids:

amphipathic: one end of the molecule is hydrophobic, the other is hydrophilic

hydrophobic regions associate with each other

hydrophilic regions associate with water

consist of four general types:

phospholipids: have hydrophobic regions composed of two fatty acids joined to glycerol or sphingosine

glycolipids: contain a simple sugar or a complex oligosaccharide at the polar ends

archaeal tetraether lipids: have two very long alkyl chains ether-linked to glycerol at both ends

sterols: compounds characterized by a rigid system of four fused hydrocarbon rings

Glycerophospholipids

glycophospholipids (aka phosphoglycerides): membrane lipids in which two fatty acids are attached in ester linkage to the first and second carbons of glycerol, and a highly polar or charged group is attached through a phosphodiester linkage to the third carbon

attachment of phosphate at one end of glycerol converts it to a chiral compound, named using D, L system

are named as derivatives of phosphatidic acid

a phosphodiester bond joins the head group to glycerol

phosphate group can bear a negative neutral, or positive charge

fatter acids can any of a wide variety

in general, glycerophospholipids contain:

a C16 or C18 fatty acid at C-1

a C18 or C20 unsaturated fatty acid at C-2

some have ether-linked fatty acids and are ether lipids

ether lipids: one of the two acyl chains is attached to glycerol in ether, rather than ester, linkage

chain may be saturated

chain may contain a double bond between C-1 and C-2 as in plasmalogens

platelet-activating factor: an ether lipid that serves as a potent molecular signal

releases from leukocytes called basophils

stimulates platelet aggregation and serotonin release

plays a role in inflammation and the allergic response

galactolipids: member of the glycolipids group that predominate in plant cells

one or two galactose residues are connected by a glycosidic linkage to C-3 of a 1,2-diacylglycerol

sphingolipids: large class of membrane phospholipids and glycolipids that are derivatives of sphingosine

have a polar head group and two nonpolar tails

contain no glycerol

contain one molecule of the long-chain amino alcohol sphingosine or one of its derivatives

ceramides are the structural parent of all sphingolipids

ceramide: compound resulting when a fatty acid is attached in amide linkage to the -NH2 on C-2; structurally similar to a diacylglycerol

C-1, C-2, and C-3 of sphingosine are structurally analogous of the three carbons of glycerol in glycerophospholipids

includes...

sphingomyelins: subclass of sphingolipids that contains phosphocline or phosphoethanolamine as their polar head group

glycosphingolipids: have head groups with 1+ sugars connected directly to the -OH at C-1 of the ceramide moiety

do not contain phosphate

occur largely in the outer face of plasma membranes

include...

cerebrosides: have a single sugar linked to ceramide

those with glucose are found in the plasma membranes of cells in nonneural tissues

those with galactose are found in the plasma membranes of cells in neural tissue

Globosides: glycosphingolipids with 2+ sugars, usually D-glucose, D-galactose, or N-acetyl-D-galactosamine

sometimes called neutral glycolipids, as they have no charge at pH 7

gangliosides: have oligosaccharides as their polar head groups and 1+ resideus of N-acetylneuraminic acid, a sialic acid, at the termini

sites of biological recognition when 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 these glycosphingolipids

Phospholipids and sphingolipids are degraded in lysosomes

phospholipases of the A type remove one of the two fatty acids

lysophospholipases remove the remaining fatty acid

lysosomal enzymes catalyze the stepwise removal of sugar units of gangliosides

genetic defects in any hydrolytic enzymes leads to accumulation of gangliosides in the cell

Sterols have four fused carbon rings

sterols: structural lipids present in the membranes of most eukaryotic cells

steroid nucleus:

consists of four fused rings

almost planar

relatively rigid

includes...

cholesterol: major sterol in animal tissues

amphipathic

polar head group

nonpolar hydrocarbon body

membrane constituents

similar to stigmasterol in plants and ergosterol in fungi

serve as precursors for products with specific biological activities

steroid hormones regulate gene expression

bile acids: polar derivatives of cholesterol that emulsify dietary fats in the intestine to make them more readily accessible to digestive lipases

Lipids have uses in the cell beyond energy storage and membranes construction.

10.3: Lipids as Signals, Cofactors, and Pigments

phosphatidylinositols and sphingosine derivatives act as intracellular signals

phosphatidylinositol (PI) and its phosphorylated derivatives regulate cell structure and metabolism

Phosphatidylinositol 4,5-Bisphosphate (PIP2)

found in the cytoplasmic face of plasma membranes

serves as a reservoir of messenger molecules that are released in response to extracellular signals

phospholipase C hydrolyzes PIP2 to IP3 and diacylglycerol (intracellular messengers)

inositol phospholipids serve as points of nucleation

signaling proteins bind specifically to PIP3 in the plasma membrane, initiating formation of multienzyme complexes at the membrane's cytosolic surface

membrane sphingolipids serve as sources of intracellular messengers

ceramide and sphingomyelin are potent regulators of protein kinases

ceramide or its derivatives are involved in the regulation of cell division, differentiation, migration, and programmed cell death

Eicosanoids carry messages to nearby cells

eicosanoids: paracrine hormones, substances that act only on cells near the point of hormone synthesis instead of being transported in the blood

involved in:

reproductive function

inflammation, fever, and pain associated with injury or disease

formation of blood clots

regulation of blood pressure

gastric acid secretion

derived from arachidonic acid

four major classes:

prostaglandins (PG)

thromboxanes (TX)

leukotrienes (LT)

lipoxins (LX)

contain a five-carbon ring

functions:

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

have a six-membered ring containing an ether

produced by platelets

function: act in the formation of blood clots and reduction of blood flow to the site of a clot

contain three conjugated double bonds

function: powerful biological signals-induces contraction of the smooth muscle lining the airways to the lung

linear and contain several hydroxyl groups along the chain

function: potent anti-inflammatory agents

Steroid hormones carry messages between tissues

steroids: oxidized derivatives of sterols

lack the alkyl chain attached to ring D of cholesterol

more polar than cholesterol

move through the bloodstream on protein carriers to target tissues

binding to highly specific receptor proteins in the nucleus triggers changes in gene expression

Vascular plants produce thousands of volatile signals

functions of volatile, lipophilic compounsd:

attract pollinators

repel herbivores

attract organisms that defend the plant against herbivores

communicate with other plants

many are derived from fatty acids or from compounds made by the condensation of isoprene units

Vitamins: compounds that are essential to the health of humans and other vertebrates but cannot be synthesized

Fat-soluble vitamins include the groups A, D, E, and K

Vitamin D3

formed in the skin in a photochemical reaction driven by the UV component of sunlight

not biologically active

converted by enzymes in the liver and kidney to calcitriol

deficiency leads to defective bone formation and the disease rickets

calcitrol: hormone that regulates calcium uptake in the intestine and calcium levels in the kidney and bone

Vitamin A1

aka all-trans-retinol

acts in processes of development, cell growth and differentiation, and vision

can be stored for some time in the body

can be converted enzymatically to all-trans-retinoic-acid

all-trans-retinoic-acid: retinoid hormone that acts through a family of nuclear receptor proteins to regulate gene expression

beta-carotene pigment is a source of vitamin A

carotenoids: natural products with a characteristic extensive system of conjugated double bonds, which makes possible their strong absorption of visible light

vitamins E and K and the lipid quinones are oxidation-reduction cofactors

deficiencies:

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: genetically engineered rice enriched in beta-carotene

Vitamin E

collective name for a group of lipids called tocopherols

tocopherols: hydrophobic compounds that contain a substituted aromatic ring and a long isoprenoid side chain

biological antioxidants

deficiencies:

cause scaly skin, muscular weakness and wasting, and sterility

very rare in humans

principal symptom is fragile erythrocytes

Vitamin K

contains an aromatic ring that undergoes a cycle of oxidation and reduction during the formation of active prothrombin

deficiencies:

slow blood clotting

extremely uncommon in humans

prothrombin: a blood plasma protein essential in blood clotting

warfarin: a synthetic compound that inhibits the formation of active prothrombin

potent rodenticide

invaluable anticoagulant drug for treating humans at risk for excessive blood clotting

aka cholecalciferol

associate with cell membranes, lipid deposits, and lipoproteins

ubiquinone (coenzyme Q) and plastiquinone: isoprenoids that function as lipophilic electron carriers in the oxidation-reduction reactions that drive ATP synthesis in mitochondria and chloroplasts, respectively

dolichols activate sugar precursors for biosynthesis

dolichols: isoprenoid alcohols that activate and anchor sugars to cellular membranes

sugar groups are then used in the synthesis of complex carbohydrates, glycolipids, and glycoproteins

allow attached sugars to participate in sugar-transfer reactions

many natural pigments are lipidic conjugated dienes

conjugated dienes: have carbon chains with alternating single and double bonds

allow the delocalization of electrons

compounds can be excited by visible light

polyketides are natural products with potent biological activities

polyketides: diverse group of lipids with biosynthetic pathways (claisen condensations) similar to those for fatty acids

secondary metabolites: compounds that are not central to an organism's metabolism but serve some subsidiary function that gives the organism and advantage

used as antibiotics, antifungals, or inhibitors of cholesterol synthesis