Chapter 3 - Part 3

CHAPTER
2
Chemistry,
Biochemistry, and Cell
Physiology
Part 3
PowerPoint® Lecture Slides prepared by

Stephen Gehnrich, Salisbury University
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Cellular Membranes
Two main roles

 Isolate cells from the environment
 Control of intracellular conditions
 Organize intracellular pathways into subcellular
compartments

Membrane Structure
Figure 2.43
Lipid Profile
 Lipid bi-layer
 Phospholipids
 Primarily phosphoglycerides
 Other lipids
 Sphingolipids
 Alter electrical properties
 Glycolipids
 Communication between cells
 Cholesterol
 Increase fluidity while decreasing permeability

Membrane Properties of Cholesterol
Figure 2.44
Membrane Heterogeneity
More PE and PS phosphoglycerides in inner leaflet

More PC phosphoglycerides in the outer leaflet
Glycolipids only in the outer leaflet
Lipid rafts
 Enriched in glycolipids and cholesterol
 More rigid and thicker

Membrane Heterogeneity
Figure 12.45
Membrane Fluidity
 Environmental conditions affect membrane fluidity

 For example, low temperature increases van der Waals
forces between lipids and restricts movement
 Homeoviscous adaptation
 Cell keeps membrane fluidity constant by altering the
lipid profile

Temperature and Membrane Fluidity
Figure 2.46
Membrane Proteins
 Can be more than half of the membrane mass

 Structural and regulatory functions
 Two main types
 Integral membrane proteins
 Tightly bound to the membrane
 Embedded in bilayer or spanning the entire membrane
 Peripheral membrane proteins
 Weaker association with the lipid bilayer

Membrane Proteins
Figure 2.47
Membrane Transport
 Cells must transport molecules across membranes

 Three main types of transport:
 Passive diffusion
 Facilitated diffusion
 Active transport
Distinguished by direction of transport, nature of the
carriers, and the role of energy

Membrane Transport
Figure 2.48
Passive Diffusion
 Lipid-soluble molecules
 No specific transporters are needed
 Molecules cross lipid bilayer
 No energy is needed
 Depends on concentration gradient
 High concentration  low concentration
 Steeper gradient results in faster rates

Facilitated Diffusion
 Hydrophilic molecules
 Protein transporter is needed
 No energy is needed
 Depends on concentration gradient
 High concentration  low concentration
 Steeper gradient results in faster rates

Facilitated Diffusion
Three main types of protein carriers:

 Ion channels
 Small pores for specific ions
 Open and close in response to cellular conditions
 “Gated” channels
 Porins
 Like ion channels, but for larger molecules
 Permeases
 Function more like an enzyme
 Carries molecule across membrane

Ion Channels
Figure 2.49
Active Transport
 Protein transporter is needed

 Energy is required
 Molecules can be moved from low to high
concentration

Active Transport
Two main types of active transport

 Primary active transport
 Direct use of an exergonic reaction
 Secondary active transport
 Couples the movement of one molecule to the
movement of a second molecule
 Distinguished by the source of energy

Primary Active Transport
 Hydrolysis of ATP provides energy

 Transporters are ATPases
 Three types
 P-type
 Pump specific ions (e.g., Na+, K+, Ca2+)
 F-type and V-type
 Pump H+
 ABC type
 Carry large organic molecules (e.g., toxins)

Secondary Active Transport
 Use energy in electrochemical gradient of one

molecule to drive another molecule against its
gradient
 Antiport or exchanger carrier: molecules move in
opposite directions
 Symport or cotransporter carrier: molecules move in
the same direction

Electrical Gradients
 All transport processes affect chemical gradients

 Some transport processes affect electrical gradients
 Electroneutral carriers
 Transport uncharged molecules or exchange an equal
number of particles with the same charge
 Electrogenic carriers
 Transfer a charge
 For example, Na+/K+ATPase  exchanges 3Na+ for
2K+

Membrane Potential (Vm)
 Difference in charge inside and outside the cell

membrane
 Concentration gradients formed by active transport
 Two main functions
 Provide energy for membrane transport
 Changes in membrane potential used by cells in cell-
to-cell signaling

Equilibrium Potential (Eion)
Each ion has its own equilibrium potential

 Ion concentration gradient
 Ion diffuses down its concentration gradient
 Eion is the Vm at which the ion is at electrochemical
equilibrium
 Depends upon the size of the concentration gradient
 Eion can be calculated using the Nernst equation
 Assumes electrochemical equilibrium

Equilibrium Potential (Eion)
Figure 2.50
Membrane Potential (Vm)
 Cell membranes are not at equilibrium

 Varying permeability
 Multiple ion gradients
 Goldman equation
 Accounts for permeability and multiple ions
 Vm is most dependent upon Na+, K+, and Cl–
 Na+/K+ ATPase maintains Na+ and K+ gradients
across membrane

Changes in Membrane Potential (Vm)
Changes in membrane permeability cause changes in

membrane potential
 Depolarization
 Cell becomes more positive on the inside
 For example, if Na+ ions enter
 Hyperpolarization
 Cell becomes more negative on the inside
 For example, if K+ ions leave

Depolarization and Hyperpolarization
Figure 2.51
Cellular Structures
 Eukaryotic cells share many common cellular

compartments
 Compartmentalization allows for regulation of
specific processes

Mitochondria
 Produce most of the cell’s ATP

 Intricate network of internal membranes
 Large surface area
 Mitochondrial reticulum
 Network of interconnected mitochondria
 Mitochondrial DNA (mtDNA)
 Some mitochondrial proteins
 Required for mitochondrial biogenesis
 Most genes for mitochondrial proteins are in the nucleus

Mitochondria
Figure 2.52
Cytoskeleton
Network of protein-based fibers

 Microfilaments
 Flexible chains of actin
 Microtubules
 Tubes of tubulin
 Intermediate filaments
 Composed of many types of monomers
Maintains cell structure
 External cell shape
 Organization of intracellular membranes
Cellular processes
For example, movement, signal transmission

Functions of the Cytoskeleton
 Maintains cell structure

 External cell shape
 Organization of intracellular membranes
 Cellular processes
 Movement
 Motor proteins
 Signal transduction

Cytoskeleton
Figure 2.23a,b
Endoplasmic Reticulum and Golgi Apparatus
 Membranous organelles
 Proteins are made on the ER
 Proteins are modified and packaged into vesicles by the
Golgi apparatus
 Vesicles carry proteins between compartments
 Vesicles are carried throughout the cell by motor proteins
moving on cytoskeletal tracks
 Contents of vesicles can be released from the cell via exocytosis
 Extracellular substances can be taken into the cell via
endocytosis

Intracellular Traffic
Figure 2.54
Extracellular Matrix
 Gel-like “cement” between cells

 Cell membranes are bonded to the matrix
 Insect exoskeleton, vertebrate skeleton, and mollusc
shells are modified extracellular matrices
 Molecules of the matrix are synthesized within the
cells and secreted by exocytosis

Molecules of the extracellular matrix

 Proteins
 Glycoproteins
 Glycosaminoglycans
 Proteoglycans

Figure 2.55
Figure 2.56
Cells can break down the extracellular matrix with

matrix metalloproteinases
Cells can move through tissues by controlling the
production and breakdown of the matrix
 For example, blood vessel growth and penetration

Physiological Genetics and Genomics
Physiological diversity resides in genes

 How genes differ between species
 How genes are regulated in individual cells
Homeostatic regulation depends upon having
 the right protein,
 in the proper place,
 at the proper time,
 with the appropriate activity

Nucleic Acids
Two types:
 DNA – deoxyribonucleic acid
 Genetic blueprint
 Genes in nucleus
 RNA – ribonucleic acid
 Read and interpret DNA to make protein
 Three main forms
 Transfer RNA (tRNA)
 Ribosomal RNA (rRNA)
 Messenger RNA (mRNA)

Nucleic Acids
 DNA and RNA are polymers of nucleotides

 linked by phosphodiester bonds
 Nucleotide
 Nitrogenous base
 Cytosine, Adenine, Guanine,Thymine (DNA only), Uracil
(RNA only)
 Sugar
 Deoxyribose (DNA), ribose (RNA)
 Phosphate

DNA
 Double-stranded a-helix
 Two strands of nucleotides linked by hydrogen bonds
 Complementary strands
 Antiparallel
 Nucleotides can form bonds with only one other
nucleotide
 A + T: two hydrogen bonds
 G + C: three hydrogen bonds

Structure of DNA
Figure 2.57
Histones
 Mammalian DNA is several meters long

 DNA is compressed by DNA-binding proteins
(histones)
 DNA in this form is referred to as chromatin
 Advantages of compression by histones
 Large amounts of DNA fit into small volumes
 Reduces damage caused by radiation and chemicals
 Must be uncompressed for DNA and RNA
synthesis

DNA Organization
 Genome
 Entire collection of DNA within a cell
 Chromosome
 Separate segments of DNA
 Genes
 DNA sequence within a chromosome
 Used to produce RNA
 Exons
 Segments of DNA that encode RNA
 Introns
 Interspersed DNA sections between exons

DNA Organization
Figure 2.58
Genome Size
Figure 2.59
Transcription
Synthesis of messenger RNA (mRNA)

 DNA is wrapped by histones
 Must be unwrapped to allow transcription
 Transcription regulators form regulatory complexes
at promoter
 Region of the gene where transcription begins
 mRNA synthesis begins

Transcription
Figure 2.60
Mature mRNA
 Primary mRNA transcript

 Exons – sequences that will code for the protein
 Introns – noncoding sequences
 Introns are removed and exons are spliced together
 mRNA is polyadenylated
 200+ adenosines are added to the 3´ end
 poly A+ tail
 mRNA is exported from the nucleus to the cytoplasm
 mRNA is ultimately degraded by nucleases (RNases)

Protein Synthesis (Translation)
 Ribosomes
 Made of rRNA and proteins
 Bound to endoplasmic reticulum
 Catalyze the formation of peptide bonds between
amino acids
 Transfer RNA (tRNA)
 Carry the amino acids that bind to a codon (three
nucleotides on mRNA)

Protein Degradation
 Proteins may have structural changes that result in

dysfunction
 Structural changes recruit enzymes that mark the
protein with a small protein called ubiquitin
 Ubitquitin-labeled protein is then bound by a large
enzyme complex called a proteasome
 Enzymes degrade the protein to amino acids

Protein Isoforms
 Variations in protein structure

 Genetic rearrangements
 Alternative splicing of exons
 Alleles
 Gene duplications
 Subsequent mutation of some copies

Origins of Protein Isoforms
Figure 2.61
Genome Duplication
Figure 2.62

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CHAPTER

PowerPoint® Lecture Slides prepared by

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Two main roles

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

More PE and PS phosphoglycerides in inner leaflet

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

 Environmental conditions affect membrane fluidity

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

 Can be more than half of the membrane mass

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

 Cells must transport molecules across membranes

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Three main types of protein carriers:

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

 Protein transporter is needed

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Two main types of active transport

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

 Hydrolysis of ATP provides energy

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

 Use energy in electrochemical gradient of one

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

 All transport processes affect chemical gradients

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

 Difference in charge inside and outside the cell

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Each ion has its own equilibrium potential

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

 Cell membranes are not at equilibrium

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Changes in membrane permeability cause changes in

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

 Eukaryotic cells share many common cellular

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

 Produce most of the cell’s ATP

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Network of protein-based fibers

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

 Maintains cell structure

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

 Gel-like “cement” between cells

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Molecules of the extracellular matrix

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Cells can break down the extracellular matrix with

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Physiological diversity resides in genes

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

 DNA and RNA are polymers of nucleotides

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

 Mammalian DNA is several meters long

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Synthesis of messenger RNA (mRNA)

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

 Primary mRNA transcript