Chapter 11 Lipids and Membranes. Lipids Biomolecules defined in terms of solubility: Insoluble in...

Chapter 11

Lipids and Membranes

Lipids

Biomolecules defined in terms of solubility: Insoluble in water but soluble in nonpolar solvents. Waxy, greasy or oily compounds.

Biological Functions: Energy Storage Structural component of cell membranes Signaling molecules

Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7th Edition, 2011

Two major classes

Saponifiable Lipids

Saponification: base hydrolysis of esters to produce carboxylic acid salt and alcohol


• Simple Lipids:– Contain fatty acids and alcohols

• Complex Lipids:– Contain multiple fatty acids,

alcohol, something else

Fatty Acids CA’s with long hydrocarbon chains (12 to 20 or

more carbons, usually even numbers) Numbered from the carboxylate end, and the a-

carbon is adjacent to the carboxylate group Terminal methyl carbon is denoted the omega (w)

carbon Components in triacylglycerols and phospholipids

Figure 11.1 Fatty Acid Structure

Section 11.1: Lipid Classes

Characteristics of Fatty Acids

1. Straight chain (unbranched) carboxylic acids

2. Comprised of 10-20 carbons

3. Usually have even number of carbons

4. Can be saturated or unsaturated

5. Usually no other functional groups

• Unsaturated fatty acids usually contain double bonds in the cis configuration, and can be mono- or poly-unsaturated

• This creates kink or bend in chain that prevents unsaturated fatty acids from packing together closely unlike saturated fatty acids

– Results in weaker intermolecular forces, lower MP’s – Usually liquid at room temp

O

O-

CH3

CH3

O

O-

unsaturated

saturated


Properties of Unsaturated Fatty Acids


• The kink or bend in chain of unsaturated fatty acids prevents from packing together closely unlike saturated fatty acids– Results in weaker intermolecular forces, lower MP’s – Increases fluidity of biological membranes

Plants and bacteria can synthesize all fatty acids they require from acetyl-CoA

The human body can synthesize nonessential fatty acids, while essential fatty acids must be acquired from the diet

Essential Fatty Acids Linoleic acid (omega-6 fatty acid) Linolenic acid (omega-3 fatty acid)


Diets rich in omega-3 fatty acids may: decrease serum cholesterol, triglycerides reduce risk of heart disease

Fish Nuts Kidney Beans

Sources of omega-3 fatty acids: Spinach Broccoli and cauliflower Oils

Eicosanoids Omega-3 and Omega-6 fatty acids are the source of Eicosanoids

Hormone-like signaling molecules Include:

Prostaglandins: Involved in inflammation, digestion, and reproduction

Thromboxanes: Involved in platelet aggregation and vasoconstriction following tissue injury

Leukotrienes: White blood cell chemoattractants; involved in vasoconstriction, edema, and bronchoconstriction


Structures of Fats and Oils


• Fats: Triglycerides from animal (saturated)• Oils: Triglycerides from vegetables (unsaturated)• These are esters (alcohol + acid)

• Alcohol derived from glycerol• Acid from fatty acids

Most common

lipids

triglyceride

Fats are solid at room temperature and have a high saturated fatty acid composition

Oils are liquid at room temperature and have a high unsaturated fatty acid composition

Figure 11.6 Space-Filling and Conformational Models of a Triacylglycerol


Roles in animals: energy storage (also in plants), insulation at low temperatures, and water repellent for some animals’ feathers and fur

Better storage form of energy for two reasons:1. Hydrophobic and coalesce into droplets; store an equivalent amount of energy in about one-eighth the space2. More reduced and thus can release more electrons per molecule when oxidized

Figure 11.5 Triacylglycerol


Reactions of Triglycerides


hydrolysis

saponification

hydrogenation

triglyceride

Ester of 3 alcohols, 3

acids

Chemical Properties of Fats and Oils


• Triglycerides exhibit chemical properties of esters and alkenes

Rxn: Hydrolysis

Breakdown of cellular fats to supply energy begins with lipase catalyzed hydrolysis reaction



Rxn: Saponification

Soapmaking (up to AD 500), by adding base (lye or aqueous extract of wood ash) to animal fat



Rxn: Hydrogenation

Results in partial hydrogenation (partially-hydrogenated vegetable oils) Semi-solids that don’t separate Crisco

Wax Esters Waxes are complex mixtures of nonpolar lipids Protective coatings on the leaves, stems, and

fruits of plants and on the skin and fur of animals Wax esters composed of long-chain fatty acids

and long-chain alcohols are prominent constituents of most waxes

Examples include carnuba (melissyl cerotate) and beeswax

Figure 11.8 The Wax Ester Melissyl Cerotate


Phospholipids Amphipathic (hydrophilic and lipophilic) with a polar head group (phosphate and other polar or charged groups) and hydrophobic fatty acids

Act in membrane formation, emulsification, and as a surfactant (lowers surface tension between liquids)

Spontaneously rearrange into ordered structures when suspended in water

Figure 11.9 Phospholipid Molecules in Aqueous Solution


Two types of phospholipids: phosphoglycerides and sphingomyelins

Sphingomyelins contain sphingosine instead of glycerol (also classified as sphingolipids)

Phosphoglycerides contain a glycerol, fatty acids, phosphate, and an alcohol

Simplest phosphoglyceride is phosphatidic acid composed of glycerol-3-phosphate and two fatty acids

Phosphatidylcholine (lecithin) is alcohol esterified to the phosphate group as choline


Phosphoglycerides


• Complex lipids• Serve as major components of cell membranes• Also known as phospholipids• Structure similar to triglycerides

triglyceride

phosphoglyceride

Phosphoglycerides


• The most common phosphoglycerides have choline, ehanolamine, or serine attached to the phosphate group.

Another phosphoglyceride, phosphatidylinositol, is an important structural component of glycosyl phosphatidylinositol (GPI) anchors

GPI anchors attach certain proteins to the membrane surface

Proteins are attached via an amide linkage

Figure 11.10 GPI Anchor


Phospholipases Hydrolyze ester bonds in glycerophospholipid

molecules Three major functions: membrane remodeling,

signal transduction, and digestion

Figure 11.11 Phospholipases


Toxic Phospholipases—various organisms use membrane-degrading phospholipases as a means of inflicting damage

Bacterial a-toxin (creates pores in cells leading to apoptosis) and necrosis from snake venom (PLA2)


Sphingolipids Complex lipid found in cell membrane Contain sphingosine instead of glycerol


Sphingomyelin is found in most cell membranes, but is most abundant in the myelin sheath of nerve cells


https://www.premedhq.com/myelin-sheath-schwann-cells

The ceramides are also precursors of glycolipids A monosaccharide, disacchaaride, or

oligosaccharide attached to a ceramide through an O-glycosidic bond

Most important classes are cerebrosides, sulfatides, and gangliosides (may bind bacteria and their toxins)

Figure 11.14a Selected Glycolipids


Glycolipids


• Another type sphingolipid• Contain carbohydrates• AKA cerebrosides due to abundance in brain tissue• No phosphate linkage

Related Diseases


• Some human diseases are related to abnormal accumulation of sphingomyelins and glycolipids

Isoprenoids Biomolecules containing repeating

five-carbon structural units, or isoprene units

Isoprenoids consist of terpenes and steroids

Terpenes are classified by the number of isoprene units they have

Monoterpenes (used in perfumes), sesquiterpines (e.g., citronella, 3 isoprene units), tetraterpenes (e.g., carotenoids, 8 isoprene units)

Figure 11.15 Isoprene


Carotenoids are the orange pigments found in plants

Mixed terpenoids consist of a nonterpene group attached to the isoprenoid group (prenyl groups)

Include vitamin K and vitamin E

Figure 11.16 Vitamin K, a Mixed Terpenoid


Steroids


Exhibit feature of other lipids (e.g., soluble in non-polar solvents) Cholesterol is most abundant steroid in human body

Essential component of cell membranes Precursor for other steroids:

Bile salts Sex hormones Vitamin D Adrenocorticoid hormones

Synthesized in liver or obtained from food May contribute to atherosclerosis

CH3

CH3

CH3

CH3

OH

CH3

Steroid Cholesterol

Cholesterol is an important molecule in animal cells that is classified as a sterol, because C-3 is oxidized to a hydroxyl group

Essential in animal membranes; a precursor of all steroid hormones, vitamin D, and bile salts

Usually stored in cells as a fatty acid ester


CH3

CH3

CH3

CH3

OH

CH3

Figure 11.19 Animal Steroids


Bile Salts

Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7th Edition, 2011; http://www.medicinenet.com/gallstones/article.htm

Yellow-brown or green liver secretion stored in gallbladder

Bile salts are released into intestine to separate large globules of lipids into smaller droplets

Bile salts also emulsify (mix immiscibles) cholesterol found in the bile for excretion

Gallstones may occur if cholesterol too high and/or bile salts too low

Steroid Hormones

http://schoolworkhelper.net/2010/07/the-endocrine-system-function-and-structure/

Hormone: Chemical produced in the cell or gland that delivers a message affecting cells in another part of the organism

Steroid hormones derived from cholesterol Two Major Steroid Hormones:

Adrenocorticoid Hormones Male and Female Sex Hormones

Steroid hormones diffuse through the cell membrane and combine with receptor proteins in the cytoplasm

Hormone-receptor complex cause cell to respond to hormone by interacting with cell DNA and stimulating protein synthesis

CH3

CH3

CH3

CH3

OH

CH3

Adrenocorticoid Hormones


Produced in adrenal glands located at top of kidneys Classified into 2 functional groups: Mineralocorticoids: Regulate concentration of ions (Na+) in body fluids

Aldosterone: most important mineralocorticoidPromotes absorption of Na+ and Cl- in kidney tubules

Glucorticoids: Enhance carbohydrate metabolism Cortisol is major glucocorticoid in human body Increases glucose and glycogen concentration in body Cortisol, cortisone and prednisolone exert anti-inflammatory effects

Used to treat rheumatoid arthritis, bronchial asthma

Male Sex Hormones

Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7th Edition, 2011; http://artofamandanelson.blogspot.com/2011/09/generating-topics-steroids.html

Male sex hormones (androgens) produced in testes Testosterone: Most important

Promotes normal growth of male genitalia and aids in development of secondary sex characteristics

Anabolic steroids banned for use by athletes include testosterone and derivatives

Use of these can lead to:Liver tumorsTesticular atrophyDecreased sperm count

Female Sex Hormones


Female sex hormones promote development of secondary sex characteristics Increase in voice pitch Increased breast size Inhibition of facial hair

Estrogens: Primary female sex hormones, play important roles in reproduction:

Estradiol Estrone Progesterone

Lipoproteins Transport lipid molecules

through the bloodstream from organ to organ

Protein components (apolipoproteins) for lipoproteins are synthesized in the liver or intestine

Figure 11.21 Plasma Lipoproteins


Lipoproteins are classified according to their density:

Chylomicrons are large lipoproteins of extremely low density that transport triacylglycerol and cholesteryl esters (synthesized in the intestines)

Very low density lipoproteins (VLDL) are synthesized in the liver and transport lipids to the tissues

Low density lipoproteins (LDL) are principle transporters of cholesterol and cholesteryl esters to tissues

High density lipoprotein (HDL) is a protein-rich particle produced in the liver and intestine that seems to be a scavenger of excess cholesterol from membranes


Properties of Unsaturated Fatty Acids


• Phospholipids form bilayer in cell membrane

Membrane lipids: Responsible for many membrane properties

Membrane fluidity refers to the viscosity of the lipid bilayer

Lipids may diffuse, or move around, within the membrane

Lipids may also flip from one side of the membrane to the other

Figure 11.25 Lateral Diffusion in Biological Membranes

Section 11.2: Membranes

The movement of molecules from one side of a membrane to the other requires a flipase

Membrane fluidity largely depends on the percentage of unsaturated fatty acids and cholesterol

Cholesterol contributes to stability with its rigid ring system and fluidity with its flexible hydrocarbon tail

Figure 11.24 Diagrammatic View of a Lipid Bilayer


Membrane Properties: Selective permeability is provided by the

hydrophobic chains of the lipid bilayer, which is impermeable to most all molecules (except small nonpolar molecules)

Membrane proteins help regulate the movement of ionic and polar substances

Small nonpolar substances may diffuse down their concentration gradient

Self-sealing is a result of the lateral flow of lipid molecules after a small disruption

Asymmetry of biological membranes is necessary for their function

The lipid composition on each side of the membrane is different


Membrane Proteins—most functions associated with the membrane require membrane proteins

Classified by their relationship with the membrane: peripheral or integral

Figure 11.26 Integral and Peripheral Membrane Proteins


Integral proteins embed in or pass through the membrane

Red blood cell anion exchanger

Peripheral proteins are bound to the membrane primarily through noncovalent interactions

Can be linked covalently through myristic, palmitic, or prenyl groups

Figure 11.27 Red Blood Cell Integral Membrane Proteins


Membrane Microdomains—lipids and proteins in membranes are not uniformly distributed

Specialized microdomains like “lipid rafts” can be found in the external leaflet of the plasma membrane

Figure 11.28 Lipid Rafts


Lipid rafts often include cholesterol, sphingolipids, and certain proteins

Lipid molecules are more ordered (less fluid) than non- raft regions

Lipid rafts have been implicated in a number of processes: exocytosis, endocytosis, and signal transduction

Figure 11.29 The Lipid Raft Environment


Membrane Function There are a vast array of membrane functions,

including transport of polar and charged substances and the relay of signals

Figure 11.30 Transport across Membranes


Membrane Transport Ions and molecules constantly move across the

plasma membrane and membranes of organelles Important for nutrient intake, waste excretion,

and the regulation of ion concentration Biological transport mechanisms are classified

according to whether they require energy


In passive transport, there is no energy input, while in active transport, energy is required

Passive is exemplified by simple diffusion and facilitated diffusion (with the concentration gradient)

Active transport uses energy to transport molecules against a concentration gradient

Figure 11.30 Transport across Membranes


Simple diffusion involves the propulsion of each solute by random molecular motion from an area of high concentration to an area of low concentration

Diffusion of gases O2 and CO2 across membranes is proportional to their concentration gradients

Facilitated diffusion uses channel proteins to move large or charged molecules down their concentration gradient

Examples include chemically gated Na+ channel and voltage-gated K+ channel


Active transport has two forms: primary and secondary

In primary active transport, transmembrane ATP-hydrolyzing enzymes provide the energy to drive the transport of ions or molecules

Na+-K+ ATPase

Figure 11.31 The Na+-K+ ATPase and Glucose Transport


In secondary active transport, concentration gradients formed by primary active transport are used to move other substances across the membrane

Na+-K+ ATPase pump in the kidney drives the movement of D-glucose against its concentration gradient

Figure 11.31 The Na+-K+ ATPase and Glucose Transport


Membrane Receptors provide mechanisms by which cells monitor and respond to changes in their environment

Chemical signals bind to membrane receptors in multicellular organisms for intracellular communication

Other receptors are involved in cell-cell recognition

Binding of ligand to membrane receptor causes a conformational change and programmed response


Chapter 11 Lipids and Membranes. Lipids Biomolecules defined in terms of solubility: Insoluble in...

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