Cholesterol

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Chapt. 10 Cell Biology and Biochemistry
Chapt. 10 Cell Biology
and Biochemistry
Student Learning Outcomes:
• Describe basic features of typical human cell
• Explain plasma membrane structure/ function
• Describe different transport proteins that permit
compounds to cross the membrane
• Explain the structure and unique function of each
organelle
• Describe the structure of the cytoskeleton
Cell
The cell:
• Lipid bilayer membrane
• Integral transport proteins
• Membrane-bound
organelles
sequester enzymes
• Cytoskeleton
• Different cell types have
different amounts of
organelles, enzymes
Fig. 10.1 typical
animal cell
Phospholipid bilayer membrane
Phospholipid bilayer membrane:
Separates contents from external environment
Fig. 10.2 typical
lipid bilayer
Mobility of phospholipids (Figure 2.23 Cooper et al)
• Lipid bilayers behave as 2-dimensional fluids:
individual molecules can rotate and move laterally
• Fluidity determined by temperature, lipid composition.
• Asymmetric distribution of specific phospholipids
Phospholipids
Glycerol lipids:
2 fatty acids,
glycerol,
phosphate;
often polar group
attached to
phosphate
Sphingolipids:
2 fatty acids,
serine,
phosphate
Fig. 10.3
phospholipids
and different
head groups
Figure 2.9
Cholesterol and steroid hormones
Animal cell membranes contain cholesterol
Hydrocarbon rings very hydrophobic, but -OH group is
weakly hydrophilic, so cholesterol is amphipathic
Cholesterol comes
from diet or body
synthesizes
steroid hormones
(e.g., estrogens and
testosterone)
are derived from
cholesterol.
Insertion of cholesterol in a membrane
Ring structure of cholesterol helps determine
membrane fluidity:
• Interactions between hydrocarbon rings and fatty acid tails
makes membrane more rigid.
• Inserts near unsaturated fatty acids
• Cholesterol reduces interaction between fatty acids,
maintains fluidity at lower temperatures.
Fig. 10.4
Membrane proteins anchored to protein mesh
Red blood cell is model membrane:
no nucleus, organelles
• Integral proteins: (hydrophobic & hydrophilic regions)
• oftenTransmembrane
• Channels
• Transporters
• Receptors
• Peripheral proteins:
• Bound to integral
• Signaling
• Structural
Fig. 10.5
ABO, Structure of glycolipids
Many cell membranes contain glycolipids:
Sugar, fatty acids, no phosphate
Also amphipathic
Cholera toxin binds glycolipids
ABO blood groups are glycolipids:
Lipids & carbohydrates
GPI anchors some
extracellular proteins:
Glycophosphatidyl inositol
has sugar inositol on
phospholipid
Other lipids anchor proteins
inside membrane
Fig. 10.6
Phospholipid bilayer membrane
Many carbohydrates are found on external surface of
plasma membrane (glycocalyx) - protective
Fig. 10.2 typical
lipid bilayer
Permeability of phospholipid bilayers
• Selective permeability of membrane allows cell to
control its internal composition.
• Some molecules diffuse across bilayer: CO2, O2, H2O,
• Steroid hormones.
• Ions, larger uncharged, or polar molecules cannot
diffuse across.
Proteins carry specific components
Proteins transport most compounds across
hydrophobic barrier of membranes
Fig. 10.7
Facilitative diffusion and transporter proteins
Fig. 10.8
Glucose transporter:
• Facilitative diffusion:
• Glucose moves down
concentration gradient
• Insulin increases number
of transporters
Gated channels regulated by stimuli
Gated channels are regulated by stimuli:
voltage, ligand binding, phosphorylation
CFTR (cystic fibrosis transmembrane conductance
regulator) is a Cl- channel
• ATP binding domains regulated by phosphorylation
• mutated in cystic fibrosis
• Still passive transport since many Cl- for 1 ATP
Fig. 10.9
Active transport uses ATP to transport items
Active transport: energy is used to transport
items independent of concentration
Primary: Na+, K+ ATPase sets up major ion gradient
(also Ca+2/ATPase pump)
Secondary: gradient is used to concentrate item
(antiport, symport or cotransport)
Fig. 10.10
Na+/K+/ATPase
Active transport – cotransporter/antiport
Active transport:
Symport: Glucose
cotransporter
• let in Na+, glucose
• Intestinal cells
Fig. 10.11
Antiport:
Band 3 of red blood cell:
• Exchanges Cl- (in) for
bicarbonate (out)
Fig. 4.9, part
Lysosomes recycle components
Lysosomes have acid hydrolases:
• digest components, eliminate, recycle
• defects -> storage diseases (ex. Tay-Sachs)
Fig. 10.12
Phagocytosis
Endocytosis: cells take up
macromolecules, fluids, and
particles such as bacteria.
Area of plasma membrane buds
off inside cell to form vesicle with
ingested material
Phagocytosis (cell eating) occurs
in specialized cell types.
Autophagy recycles damaged
organelles
Pinocytosis (cell drinking) is a
property of all eukaryotic cells.
Receptor-mediated Endocytosis
Receptor-mediated endocytosis: mechanism for
selective uptake of specific macromolecules.
• Cell surface receptors in regions (clathrin-coated pits).
• Pits bud as clathrin-coated vesicles, fuse to form lysosome
Endocytosis
Receptor-mediated endocytosis first elucidated in
patients with familial hypercholesterolemia
• lack LDL receptors on cell surface
• very high blood levels of cholesterol
• Cholesterol transported in
bloodstream mostly as
low-density lipoprotein, LDL.
• 1500 cholesterols
• 800 phospholipids
• 1 protein
Mitochondria
Mitochondria: powerhouses
• Have DNA, divide
• Two membrane layers
• Oxidative phosphorylation
• enzymes to make ATP
Fig. 10.13
One mitochondrion,
Two mitochondria
Peroxisomes
Peroxisomes:
• Single-membrane-enclosed organelles contain
diverse metabolic enzymes (peroxins)
• Oxidative reactions, as fatty acid degradation
• Generate hydrogen peroxide (H2O2)
• No genome
Nucleus
Nucleus: DNA, genome
• 2-layer membrane
• Nuclear pores for transport
Fig. 10.14
Endoplasmic reticulum
Endoplasmic reticulum:
RER (rough): ribosomes
make proteins destined for
modification, transport to
Golgi, vesicles, secreted
SER (smooth): enzymes
make lipids, detoxify drugs
Fig. 10.15
The Golgi Apparatus
Distinct regions of Golgi:

cis Golgi network—receives molecules from ER
 medial and trans Golgi stacks— most modifications here
 trans Golgi network—sorting and distribution
Cytoskeleton
Cytoskeleton:
• Strength, shape, movement
• Microtubules
 a,
b heterodimers
• Intermediate filaments
• Actin filaments
Dynamic microtubules move
organelles, vesicles,
chromosomes
Fig. 10.16
Actin filaments
Actin fibers:
• Dynamic
•
G-actin subunits (bound ATP)
add to the F-actin polymer
• Provide shape
•
Ex. under rbc membrane bound
to spectrin (fig. 10.5)
• Muscle movement with myosin
Fig. 10.17
Intermediate filaments
Intermediate filaments IF:
• Strong fibers
• Ex. Keratin, nuclear lamins
• Mutated LMNA -> HutchinsonGilford Progeria – premature aging
Fig. 10.18
Key concepts
Key concepts:
• Cell is basic unit of living organisms
•
unique features define tissue functions
• Common feature is plasma membrane:
•
phospholipid bilayer, semi-permeable
• Eukaryotes have intracellular organelles:
• Diverse structures and functions
Clinical comments
Dennis Veere - Cholera A toxin binds receptor,
enters cell and moves with G protein Arf (ADPribosylation factor); modifies Ga-subunit of G
protein, activates PKA, and the CFTR Cl- channel
opens (Na+ and Cl- and water exit; rapid efflux of
water -> major diarrhea; give IV with Na+, glucose
Lotta Topaigne - colchicine aided gout; blocks
microtubules, derease phatogytosis, lysosomal
enzymes and less inflammmation
allopurinol decreases urate production
Tay-Sachs - a lysosomal storage disease
Review question
Review question:
Transmembrane proteins can best be described by
which of the following?
a. They can usually be dissociated from membranes
without disrupting the lipid bilayer
b. They are classified as peripheral membrane
proteins
c. They contain hydrophobic amino acid residues at
their carboxy terminus.
d. They contain hydrophilic amino acid residues
extending into the lipid bilayer
e. They contain membrane-spanning regions that are
a-helices
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