reginald h. garrett charles m. grisham
TRANSCRIPT
Reginald H. Garrett
Charles M. Grisham
Chapter 8
Lipids
What is the structure, chemistry, and
biological function of lipids?
Outline
• What are the structures and chemistry of fatty acids?
• What are the structures and chemistry of triacylglycerols?
• What are the structures and chemistry of glycerophospholipids?
• What are sphingolipids神經脂, and how are they important for higher animals?
• What are waxes, and how are they used?
• What are terpenes萜烯, and what is their relevance to biological systems?
• What are steroids, and what are their cellular functions?
• How do lipids and their metabolites act as biological signals?
• What can lipidomics tell us about cell, tissue, and organ physiology?
Classes of Lipids
All biological lipids are amphipathic
• Fatty acids
• Triacylglycerols
• Glycerophospholipids
• Sphingolipids
• Waxes
• Isoprene-based lipids (including steroids)異戊二烯
8.1 What Are the Structures and Chemistry
of Fatty acids?
Know the common names and structures for fatty
acids up to 20 carbons long
• Saturated
• Lauric acid (12 C)月桂酸
• Myristic acid (14 C)肉豆蔻酸
• Palmitic acid (16 C)棕櫚酸
• Stearic acid (18 C)硬脂酸
• Arachidic acid (20 C)花生酸
8.1 What Are the Structures and Chemistry
of Fatty acids?
• Unsaturated fatty acids
• Palmitoleic acid (16:1)棕櫚油酸
• Oleic acid (18:1)
• Linoleic acid (18:2)亞麻油酸
• -Linolenic acid (18:3)次亞麻油酸 n-3
• -Linolenic acid (18:3) n-6
• Arachidonic acid (20:4)花生四烯酸
◎
8.1 What Are the Structures and Chemistry
of Fatty acids?
8.1 What Are the Structures and Chemistry
of Fatty acids?
•Fatty acids are comprised of
alkyl chains terminated by
carboxylic acid groups.
•Shown here is palmitic acid, a
16-carbon saturated fatty acid.
•The term “saturated” indicates
that the acyl chain is fully
reduced, i.e., saturated with
hydrogens and electrons.
Figure 8.1
8.1 What Are the Structures and Chemistry
of Fatty acids?
Figure 8.1 The structures of typical saturated fatty acids.
8.1 What Are the Structures and Chemistry
of Fatty acids?
Figure 8.1 The structures of typical unsaturated fatty acids.
8.1 What Are the Structures and Chemistry
of Fatty acids?
Figure 8.1 The structures of typical unsaturated fatty acids.
8.1 What Are the Structures and Chemistry
of Fatty acids?
Structural consequences of unsaturation
• Saturated chains pack tightly and form more
rigid, organized aggregates (i.e., membranes)
• Unsaturated chains bend and pack in a less
ordered way, with greater potential for motion
Fats in the human diet vary widely in their
composition
Diets high in trans fatty acids raise plasma
LDL cholesterol levels
Figure 8.2 Structures
of elaidic acid and
vaccenic acid, two
trans fatty acids.
Trans fatty acids are
present at low levels in
dairy and meat
products from ruminant
animals. “Partially
hydrogenated” fats in
foods contain much
higher amounts.
反油酸
異油酸
8.2 What Are the Structures and Chemistry
of Triacylglycerols?
Triacylglycerols are also called triglycerides
• They are a major energy source for many
organisms
• Why?
• Most reduced form of carbon in nature
• No solvation needed
• Efficient packing
8.2 What Are the Structures and Chemistry
of Triacylglycerols?
Most of the fatty acids in
plants and animals exist in
the form of triacylglycerols.
If all three fatty acids are
the same, the molecule is
called a simple
triacylglycerol.
Figure 8.3 Triacylglycerols are formed from glycerol
and fatty acids.
8.2 What Are the Structures and Chemistry
of Triacylglycerols?
Mixed triacylglycerols
contain two or three
different fatty acids.
Figure 8.3 Triacylglycerols are formed from glycerol
and fatty acids.
Polar Bears Prefer Nonpolar Food
Polar Bears Prefer Nonpolar Food
Polar bears face an ironic dilemma. They are
surrounded by water they cannot use. Ice and
snow are too cold and seawater is too salty. They
produce all the water they need from metabolism
of fat: (CH2) + 1.5O2 → CO2 + H2O
Interestingly, adult polar bears consume only fat
(from seals they catch). By not consuming
protein (and merely recycling their own proteins
into new ones), they have no need to urinate or
defecate and go for months without doing so, thus
saving precious body water.
8.3 What Are the Structures and Chemistry
of Glycerophospholipids
• A 1,2-diacylglycerol that has a phosphate group esterified at carbon 3 of the glycerol backbone is a glycerophospholipid
Glycerophospholipids are phospholipids but not necessarily vice versa
• Know the names and structures in Figure 8.6
• Understand the prochirality of glycerol
• Remember that, if a phospholipid contains unsaturation, it is most likely at the 2-position
◎
8.3 What Are the Structures and Chemistry
of Glycerophospholipids
Figure 8.4 Phosphatidic acid, the parent compound for
glycerophospholipids.
Glycerophospholipids are essential components of cell
membranes and are also found in other parts of cells.
8.3 What Are the Structures and Chemistry
of Glycerophospholipids
Figure 8.6 The structure of phosphatidylcholine. The core of
the structure is shown here with a blue background. In the
rest of Figure 8.6, the core is displayed using this blue motif.
8.3 What Are the Structures and Chemistry
of Glycerophospholipids
Figure 8.6 Structures of several
glycerophospholipids and a space-
filling model of phosphatidylglycerol.
8.3 What Are the Structures and Chemistry
of Glycerophospholipids
Figure 8.6 Structures of several
glycerophospholipids and a space-
filling model of phosphatidylinositol.
肌醇
Phosphatides Exist in Many Varieties
Figure 8.7 A space-filling model
of 1-stearoyl-2-oleoyl-
phosphatidylcholine.
Unsaturated fatty acids are
found typically at the 2-
position of the glycerol
backbone. It is rare to find
unsaturated fatty acids at the
1-position.
Ether Glycerophospholipids Include PAF
and Plasmalogens
Ether glycerophospholipids possess an ether
linkage instead of an acyl group at the C-1
position of glycerol.
•See Figure 8.8
•
•Plasmalogens縮醛磷脂 are ether
glycerophospholipids in which the alkyl chain is
unsaturated
◎
Alzheimer's Disease/ Down syndrome
Ether Glycerophospholipids Include PAF
and Plasmalogens
Figure 8.9 The structure
of a choline plasmalogen.
Ether Glycerophospholipids Include PAF
and Plasmalogens
Figure 8.8 A 1-alkyl-2-acyl-
phosphatidylethanolamine (an
ether glycerophospholipid).
Ether Glycerophospholipids
•Platelet activating factor (PAF) is an ether
glycerophospholipid
•PAF is a potent biochemical signal molecule
•Note the short (acetate) fatty acyl chain at the
C-2 position in PAF
◎
Ether Glycerophospholipids Include PAF
and Plasmalogens
Figure 8.8 The structure of 1-alkyl-2-acetyl-
phosphatidylcholine (PAF).
8.4 What Are Sphingolipids and How Are
They Important for Higher Animals?
• Sphingolipids represent another class of lipids
found frequently in biological membranes
• Sphingosine鞘氨醇, an 18-carbon alcohol,
forms the backbone of these lipids rather than
glycerol, sphingomyelin, 神經鞘磷脂
• A fatty acid joined to sphingosine in amide
linkage forms a ceramide神經醯胺• Glycosphingolipids are ceramides with one or
more sugars in beta-glycosidic linkage at the 1-
hydroxyl group
8.4 What Are Sphingolipids and How Are
They Important for Higher Animals?
Figure 8.10 Sphingolipids are based
on the structure of sphingosine.
Sphingosine is an 18-carbon alcohol.
Fatty acids joined in amide linkage at
the highlighted nitrogen form
ceramides.
8.4 What Are Sphingolipids and How Are
They Important for Higher Animals?
Figure 8.10 A ceramide is formed by
joining a fatty acid in amide linkage to
a sphingosine.
8.4 What Are Sphingolipids and How Are
They Important for Higher Animals?
• Glycosphingolipids with one sugar are
cerebrosides腦苷脂
• Ceramides with 3 or more sugars, one of
which is a sialic acid唾液酸, are
gangliosides神經節苷脂.
8.4 What Are Sphingolipids and How Are
They Important for Higher Animals?
Figure 8.10 A ceramide with
a phosphocholine head
group is a choline
sphingomyelin.
神經鞘脂質
多發性硬化症Multiple Sclerosis
8.4 What Are Sphingolipids and How Are
They Important for Higher Animals?
Figure 8.10 A ceramide with a single
sugar is a cerebroside.
8.4 What Are Sphingolipids and How Are
They Important for Higher Animals?
Figure 8.10 Gangliosides are ceramides with three or more
sugars esterified, one of which is a sialic acid.
Gangliosides are
important
components of
muscle and
nerve
membranes.
◎
Tay–Sachs disease
8.5 What Are Waxes, and How Are They
Used?
Waxes are esters of long-chain alcohols with long-chain fatty acids
• Waxes are insoluble in water, due to their mostly hydrocarbon composition
• Animal skin and fur are wax-coated and are water-repellant
• Leaves of many plants and bird feathers are similarly water-repellant
• Carnauba wax, from a palm tree in Brazil, is a hard wax used for high-gloss finishes for automobiles, boats, floors, and shoes 棕梠蠟
• Lanolin is a wool wax used in cosmetics, such as Oil of Olay, named for its lanolin content
Triacontanol palmitate is the principal
component of beeswax.
8.5 What Are Waxes, and How Are They
Used?
Figure 8.11 Waxes consist of long-chain alcohols esterified to
long-chain fatty acids. Triacontanol palmitate is the principal
component of beeswax.
8.6 What Are Terpenes, and What is Their
Relevance to Biological Systems?
Terpenes are a class of lipids formed from combinations of isoprene units
• “Isoprene” is 2-methyl-1,3-butadiene
• Monoterpenes consist of two isoprene units
• Sesquiterpenes consist of three isoprenes
• A diterpene consists of four isoprene units
• All steroids (including cholesterol and the steroid hormones) are terpene-based molecules
8.6 What Are Terpenes, and What is Their
Relevance to Biological Systems?
•Note the two possible linkage modes:•“head-to-tail”•“tail-to-tail”
Figure 8.12 The structure of isoprene (2-methyl-1,3-butadiene)
and the structure of head-to-tail and tail-to-tail linkages.
Isoprene itself can be formed by distillation of natural rubber, a
linear head-to-tail polymer of isoprene units.
8.6 What Are Terpenes, and What is Their
Relevance to Biological Systems?
Figure 8.13 Many monoterpenes are readily recognized by
their characteristic flavors or odors (limonene in lemons;
citronellal in roses and perfumes; menthol used in cough drops.
8.6 What Are Terpenes, and What is Their
Relevance to Biological Systems?
Figure 8.13 The
diterpenes include retinal
(the visual pigment in
rhodopsin), and phytol
(found in chlorophyll.
Gibberellic acid is a plant
hormone.
植醇
phytanic acid
植烷酸 a-oxidation
8.6 What Are Terpenes, and What is Their
Relevance to Biological Systems?
Figure 8.13 The
triterpene
lanosterol is a
constituent of
wool fat and is
also a precursor
to cholesterol and
the other steroids.
Lycopene is a
carotenoid found
in ripe fruit,
especially
tomatoes.
◎
Long-chain polyisoprenoid molecules serve
several functions in various organisms
Figure 8.14 Dolichol phosphate is an initiation point for
synthesis of carbohydrate polymers in animals. In bacteria,
undecaprenol (aka bactoprenol) delivers sugars for synthesis
of cell wall components.
◎
Coumadin or Warfarin – Agent of Life and
Death
Coumadin is an oft-
prescribed anticoagulant
used by those as risk of
heart attacks. Warfarin is
a common rodent poison.
They are one and the
same molecule,
developed by Karl Paul
Link at the Wisconsin
Alumni Research
Foundation (WARF – thus
the latter name).
The key to both these uses is the action of
coumadin/warfarin as an antagonist of vitamin K in the body.
Coumadin or Warfarin – Agent of Life and
Death
• Vitamin K is required for
carboxylation of Glu residues on
proteins of the blood clotting
cascade.
• Vitamin K is oxidized in these
reactions and must be reductively
recycled.
• Coumadin/warfarin inhibits vitamin
K epoxide reductase, depleting the
cell’s supply of reduced vitamin K,
and thus inhibits the blood clotting
cascade.
◎
The Membranes of Archaea Are Rich in
Isoprene-Based Lipids
Archaea are found primarily in harsh environments, and are
ideally adapted to these stressful conditions. Isoprene-based
lipids such as caldarchaeol completely span the cell
membrane, providing exceptional membrane stability.
Figure 8.15 The structure of caldarchaeol, an isoprene-
based lipid found in archaea.
8.7 What Are Steroids, and What Are Their
Cellular Functions?
• Steroids are polyprenyl (isoprene-based)
molecules built on a core structure of three 6-
membered rings and one 5-membered ring, all
fused together
• Cholesterol is the most common steroid in
animals and precursor for all other steroids in
animals
• Steroid hormones serve many functions in
animals - including salt balance, metabolic
function and sexual function
8.7 What Are Steroids, and What Are Their
Cellular Functions?
Figure 8.16 The structure of
cholesterol, shown with steroid ring
designations and carbon numbering.
8.7 What Are Steroids, and What Are Their
Cellular Functions?
Figure 8.17 The structures of several important sterols
derived from cholesterol.
Cortisol provides control of carbohydrate, protein, and lipid
metabolism
Testosterone is the primary male sex steroid hormone
Estradiol is the primary female sex steroid hormone
Progesterone is a precursor of testosterone and estradiol
8.7 What Are Steroids, and What Are Their
Cellular Functions?
Figure 8.17 The structures of several important sterols
derived from cholesterol.
The bile acids, including cholic acid and deoxycholic acid,
are detergent molecules secreted in bile from the
gallbladder that assist in the absorption of dietary lipids in
the intestine.
◎
8.8 How Do Lipids and Their Metabolites
Act as Biological Signals?
• Glycerophospholipids and sphingolipids play
important roles as chemical signals in and on cells
• Lipid signals act locally, either within the cell where
they are made or on nearby cells
• These signals typically initiate a cascade of reactions
with multiple effects
• The lifetimes of these signals are usually very short
• The creation and breakdown of lipid signals is
carefully regulated and timed
• Some of the reactions that produce these signals are
shown on the next slide
8.8 How Do Lipids and Their Metabolites
Act as Biological Signals?
Figure 8.18 Phospholipases
A1 and A2 cleave fatty acids
from a glycerophospholipid,
producing lysophospholipids.
Phospholipases C and D
hydrolyze on either side of the
phosphate in the polar head
group.
◎
8.8 How Do Lipids and Their Metabolites
Act as Biological Signals?
A diamondback rattlesnake
8.8 How Do Lipids and Their Metabolites
Act as Biological Signals?
The Indian cobra
Phospholipases are
components of the
venoms of many
poisonous snakes.
8.8 How Do Lipids and Their Metabolites
Act as Biological Signals?
• Glycerophospholipid breakdown produces a variety
of signal products
• Arachidonic acid
• Lysophosphatidic acid
• Diacylglycerol
• Inositol phosphates, including inositol-1,4,5-trisP
8.8 How Do Lipids and Their Metabolites
Act as Biological Signals?
Figure 8.19 Modification and breakdown of
glycerophospholipids produce a variety of signals and
regulatory effects.
8.8 How Do Lipids and Their Metabolites
Act as Biological Signals?
Figure 8.19 Detail◎
8.8 How Do Lipids and Their Metabolites
Act as Biological Signals?
Figure 8.19 Detail
Plant Sterols and Stanols – Natural
Cholesterol Fighters
Dietary guidelines for optimal health call for reducing
cholesterol intake. Eating plant sterols and stanols can play
a role. These cholesterol mimics bind to cholesterol
receptors on intestinal cells and block absorption of
cholesterol itself. (Plant sterols and stanols are not
themselves absorbed.)
(Note: Stanols are fully reduced sterols.)◎
Plant Sterols and Stanols – Natural
Cholesterol Fighters
Raisio Group, a Finnish company, has developed Benecol, a
stanol ester spread (available in many U.S. supermarkets) that
can lower LDL cholesterol by up to 14% if consumed daily (see
graph on next slide)
◎
Plant Sterols and Stanols – Natural
Cholesterol Fighters
Serum cholesterol
before and after
consumption of Benecol.
Green circles: 0g/day
Red squares: 2.6g/day
Blue triangles: 1.8g/day
17β-Hydroxysteroid Dehydrogenase 3
Deficiency
Deficiency of 17β-Hydroxysteroid Dehydrogenase 3 reduces
production of testosterone and can result in development of
male pseudohermaphroditism◎
Sphingolipids can be modified or broken
down to produce chemical signals
Sphingosine can be
phosphorylated to produce
sphingosine-1-phosphate (S1P)
inside cells.
Figure 8.20 Structures of
sphingosine-1-phosphate
(S1P) and fumonisin B1
Sphingolipids can be modified or broken
down to produce chemical signals
S1P may either exert a
variety of intracellular
effects or may be
excreted from the cell,
where it can bind to
membrane receptor
proteins, either on
adjacent cells or on the
cell from which it was
released.
Fumonisin inhibits sphingolipid biosynthesis
Fumonisin is a common fungal contaminant of corn and
corn-based products that inhibits sphingolipid biosynthesis.
Fumonisin can trigger esophageal cancer in humans and
leukoencephalomalacia, a fatal disease in horses.
8.9 What Can Lipidomics Tell Us about
Cell, Tissue, and Organ Physiology?• Many human diseases involve the disruption of lipid
metabolic enzymes and pathways.
• New techniques have made possible the global
analysis of lipids and their interacting protein partners
in organs, cells, and organelles – an approach termed
lipidomics
• Typical cells contain over a thousand different lipids
• Complete understanding of lipid function will require
the determination of which lipids are present and in
what concentrations
• Cellular lipidomics provides a framework for
understanding the myriad roles of lipids