Transcript Chapter 11

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
Two major
classes 
Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7 th Edition, 2011
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
Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7 th Edition, 2011
Section 11.1: Lipid Classes
Figure 11.1 Fatty
Acid Structure
Fatty Acids
CA’s with long hydrocarbon chains (12 to 20 or more
carbons, usually even numbers)
Numbered from the carboxylate end, and the acarbon is adjacent to the carboxylate group
Terminal methyl carbon is denoted the omega (w)
carbon
Components in triacylglycerols and phospholipids
Characteristics of Fatty Acids
1.
2.
3.
4.
5.
Straight chain (unbranched) carboxylic acids
Comprised of 10-20 carbons
Usually have even number of carbons
Can be saturated or unsaturated
Usually no other functional groups
O
O
-
unsaturated
H3C
saturated
O
H3C
• 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
Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7 th Edition, 2011
-
O
Section 11.1: Lipid Classes
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
Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7 th Edition, 2011
Section 11.1: Lipid Classes
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
Sources of omega-3 fatty acids:
 Fish
 Nuts
 Kidney Beans
 Spinach
 Broccoli and cauliflower
 Oils
Section 11.1: Lipid Classes
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
Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7 th Edition, 2011
Section 11.1: Lipid Classes
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
Section 11.1: Lipid Classes
Figure 11.5 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
space
2. More reduced and thus can release more electrons
per molecule when oxidized
Reactions of Triglycerides
Ester of 3
alcohols, 3
acids
triglyceride
hydrolysis
saponification
Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7 th Edition, 2011
hydrogenation
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
Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7 th Edition, 2011
Chemical Properties of Fats and Oils
Rxn: Saponification
Soapmaking (up to AD 500), by adding base (lye or aqueous
extract of wood ash) to animal fat
Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7 th Edition, 2011
Chemical Properties of Fats and Oils
Rxn: Hydrogenation
Results in partial hydrogenation (partially-hydrogenated vegetable
oils)
Semi-solids that don’t separate
 Crisco
Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7 th Edition, 2011
Section 11.1: Lipid Classes
Figure 11.8 The Wax Ester
Melissyl Cerotate
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
Section 11.1: Lipid Classes
Figure 11.9 Phospholipid
Molecules in Aqueous
Solution
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
Section 11.1: Lipid Classes
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
Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7 th Edition, 2011
Phosphoglycerides
• The most common phosphoglycerides have choline, ehanolamine, or serine
attached to the phosphate group.
Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7 th Edition, 2011
Section 11.1: Lipid Classes
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
Section 11.1: Lipid Classes
Figure 11.11 Phospholipases
Phospholipases
Hydrolyze ester bonds in glycerophospholipid
molecules
Three major functions: membrane remodeling, signal
transduction, and digestion
Section 11.1: Lipid Classes
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)
Section 11.1: Lipid Classes
Sphingolipids
Complex lipid found in cell membrane
Contain sphingosine instead of glycerol
Section 11.1: Lipid Classes
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
Section 11.1: Lipid Classes
Figure 11.14a Selected
Glycolipids
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)
Glycolipids
•
•
•
•
Another type sphingolipid
Contain carbohydrates
AKA cerebrosides due to abundance in brain tissue
No phosphate linkage
Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7 th Edition, 2011
Related Diseases
• Some human diseases are related to abnormal accumulation of
sphingomyelins and glycolipids
Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7 th Edition, 2011
Section 11.1: Lipid Classes
Figure 11.15
Isoprene
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)
Section 11.1: Lipid Classes
Figure 11.16 Vitamin K, a
Mixed Terpenoid
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
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
HO
Steroid
Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7 th Edition, 2011
CH3
Cholesterol
Section 11.1: Lipid Classes
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
HO
CH3
Section 11.1: Lipid Classes
Figure 11.19 Animal Steroids
Bile Salts
 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
Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7 th Edition, 2011; http://www.medicinenet.com/gallstones/article.htm
Steroid Hormones
 Hormone: Chemical produced in the cell or gland that delivers a message affecting
cells in another part of the organism
CH3
 Steroid hormones derived from cholesterol
 Two Major Steroid Hormones:
CH3
 Adrenocorticoid Hormones
CH3
CH3
 Male and Female Sex Hormones
HO
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
http://schoolworkhelper.net/2010/07/the-endocrine-system-function-and-structure/
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 mineralocorticoid
 Promotes 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
Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7 th Edition, 2011
Male Sex Hormones
 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 tumors
 Testicular atrophy
 Decreased sperm count
Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7 th Edition, 2011; http://artofamandanelson.blogspot.com/2011/09/generating-topicssteroids.html
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
Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7 th Edition, 2011
Section 11.1: Lipid Classes
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
Section 11.1: Lipid Classes
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
Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7 th Edition, 2011
Section 11.2: Membranes
Figure 11.25 Lateral
Diffusion in Biological
Membranes
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
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
Section 11.2: Membranes
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
Section 11.2: Membranes
Figure 11.26 Integral and
Peripheral Membrane Proteins
Membrane Proteins—most functions associated with
the membrane require membrane proteins
Classified by their relationship with the membrane:
peripheral or integral
Section 11.2: Membranes
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
Section 11.2: Membranes
Figure 11.28 Lipid Rafts
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
Section 11.2: Membranes
Figure 11.29 The Lipid
Raft Environment
Lipid rafts often include cholesterol, sphingolipids, and
certain proteins
Lipid molecules are more ordered (less fluid) than nonraft regions
Lipid rafts have been implicated in a number of
processes: exocytosis, endocytosis, and signal
transduction
Section 11.2: Membranes
Figure 11.30 Transport
across Membranes
Membrane Function
There are a vast array of membrane functions,
including transport of polar and charged substances
and the relay of signals
Section 11.2: 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
Section 11.2: Membranes
Figure 11.30 Transport
across Membranes
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
Section 11.2: 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
Section 11.2: Membranes
Figure 11.31 The Na+-K+ ATPase
and Glucose Transport
Active transport has two forms: primary and secondary
In primary active transport, transmembrane ATPhydrolyzing enzymes provide the energy to drive the
transport of ions or molecules
Na+-K+ ATPase
Section 11.2: Membranes
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
Section 11.2: Membranes
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