Fall, 2012
BIOL 130
Lecture Notes
This booklet contains the notes that will be presented as part of the online modules. For
copyright reasons, the figures that will be shown along with the notes cannot be
reproduced. However, most of these figures come from the required course text, Cell and
Molecular Biology: Concepts and Experiments, 6th edition, Gerald Karp, John Wiley and
Sons, 2010. The notes point out where in the course text the figures that illustrate a
particular subject may be found. The exam questions come from the lecture notes.
Organization of Lecture Notes
There are 24 units or lectures (sometimes 1 unit takes less or more than the expected 1
lecture period). These 24 units or lectures are divided into six modules. Each module
begins with an outline for the module. A number, a letter and another number are used to
designate respectively a module, a lecture and a section. Thus 2f3 means module 2, unit f
of module 2 and section 3 of lecture f. These notations correspond to material on the
Learn website.
Using Lecture Notes
A useful way to use this booklet is to make notes in it and/or to make notes in it while
listening to the Biology 130 modules.
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1f Proteins
1f1) Protein functions
1f2) Amino Acids
1f3) Peptide bond
1f4) Primary Structure of Proteins
1f5) Protein confirmation
1f6) Secondary Structure of Proteins
1f7) Tertiary Structure of Proteins
1f8) Motifs vs. Domains
1f9) Quaternary Structure of Proteins
1f10) Covalent Modifications of Proteins
1f11) Other Structural Features of Proteins
1f12) Multiprotein Complexes
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All living things are composed of one or more units called cells.
Each cell is capable of maintaining its vitality independent of the rest
(i.e. Smallest clearly defined unit of life is the cell.)
Cells can arise only from other cells.
Cells are highly complex and organized but all are enclosed by a physical barrier
cell membrane.
Blue print DNA (genetic program).
Cells acquire and utilize energy.
Cells carry out a variety of chemical reactions.
Cells are capable of producing more of themselves.
Cells engage in numerous mechanical activities.
Cells are able to respond to stimuli.
Cells are capable of self-regulation.
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2.
3.
Cytoskeleton
microtubules pipe-like cylinders about 20-25 nm in diameter.
microfilaments cylinders about 5 nm in diameter.
intermediate filaments cylinders or fibers 10 nm in diameter.
4.
5.
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B.
C.
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Covalent bonds
principal is that an atom is most stable when its outermost electron shell is filled.
2.
number of bonds depends on number of electrons needed to fill its outer shell.
(Karp: p. 32 Fig. 2.1)
C = carbon 4 covalent bonds or their equivalent in double and triple bonds
H = hydrogen 1 bond
O = oxygen 2 bonds
S = sulfur 2 bonds in organic molecules
N = nitrogen 3 bonds
P = phosphorus 5 (3) bonds
1b 2) Polar molecules
1.
2.
3.
4.
Certain atoms attract the shared electron pairs to a greater extent than other atoms.
This property of attracting electrons is called electronegativity.
When a covalent bond has an uneven distribution of charge, it is called a polar bond.
If molecule is appropriately shaped, a polar bond may result in a polar molecule or
dipole.
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H2O because of the angles of its bonds the H2O molecule is not a linear molecule
but, instead, has an angular shape.
This gives H2O molecule a partially negative end and two partially positive wings
so H2O is a polar molecule.
Molecules in which there is little or no separation of negative and positive charges
are nonpolar e.g. O2.
1b 3) Ionization
1b 4) Free radicals
Ionic bonds
Hydrogen bonds
Hydrophobic bond or hydrophobic interactions
Ionic bonds
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Functional groups:
1.
2.
3.
Particular groupings of atoms that often behave as a unit and give organic
molecules their properties.
Common functional groups (Karp: p. 41 Table 2.3 structural formula)
Examples: CH3, OH, COOH, NH2 (these are condensed structural form.)
Common linkage between functional groups.
Ester bonds formed between carboxylic acid and alcohols.
Amide bonds formed between carboxylic acid and amines.
Important because forms weak interactions with so many different chemical groups.
Water as a solvent
Dipolar nature of H2O makes it an ideal solvent for a variety of substances.
1.
2.
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Such as benzene, ether, and chloroform are readily miscible only with one
another or with other nonpolar solvents.
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Small, diverse organic molecules that are insoluble in H2O but soluble in nonpolar
organic solvents. e.g. chloroform or benzene.
Hydrophobic or contain significant hydrophobic regions.
3.
4.
Source of energy in the diet and serve to store energy in the body.
e.g. fats and oils
Some hormones (chemical messengers) are lipids.
e.g. steroids and prostaglandins.
Prostaglandins usually act in an autocrine and paracrine fashion whereas steroid
hormones act in an endocrine fashion
Many vitamins are lipids.
e.g. vitamins A, D, E
The basic structural elements of biological membranes.
e.g. phospholipids
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When all carbon atoms of a fatty acid chain are joined by single covalent bonds, the
compound is saturated.
O
CH3 - (CH2) n - C - OH
If one or more double bonds are present between carbons in the chain, the
compound is unsaturated.
O
CH3 - C = C - (CH2) n - C - OH
H H
1c 5) Fats and oils (triacylglycerols) (Karp: Fig. 2.19a, c & d)
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1.
2.
3.
1d 2) Monosaccharides
ketone
HC=O
R1
C=0
R2
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Isomers which have the same bonding sequence but which differ in how the atoms
are arranged in space.
Tetrahedral nature of carbon atom can lead to asymmetry in many organic
molecules (Karp: p. 43 Fig. 2.13).
This can lead to stereoisomers
Only very small amounts of monosaccharides are found in open chain form.
Most molecules are heterocyclic ring structures.
Rings result from intramolecular reactions between very active carbonyl group and
OH group on next to last carbon.
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Principal food reserve in animals and fungi: usually stored in liver and muscle of
animals.
-glucose units, mostly linked 1-4, but highly branched via frequent 1-6 linkages
1d 6) Structural polysaccharides
Cellulose (Karp: p. 45 Fig. 2.17c)
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Consist of 3 units:
A nitrogen base
A pentose sugar
A phosphate group
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Coenzymes are nonprotein substances that are required for enzyme action.
=
=
=
=
Chain of ribonucleotides.
Joined by 3'-5' phosphodiester linkage or bond.
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Chain of deoxyribonucleotides.
Joined by 3'-5' phosphodiester linkage or bond.
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H N C C OH
R
amino group
carboxyl group
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links -amino group of one amino acid with -carboxyl group of adjoining amino acid.
the linkage in dipeptides and in polypeptides.
R groups are not involved.
1f 5) Protein confirmation
Results from hydrogen bonding between the oxygen of one peptide group and the
nitrogen of another peptide group.
Secondary, tertiary, and quaternary structure describes confirmation.
R groups are not involved.
Fixed configuration of the polypeptide backbone.
Secondary structure is limited to a small number of conformations.
Two common secondary structures.
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Each amino acid is hydrogen bonded to its fourth neighbor on both sides.
pleated sheets or -pleated sheets (Karp: p. 55 Fig. 2.31)
Polypeptide chains of pleated sheets are stretched out and lie side by side, either
parallel or anti-parallel to one another.
Bonded groups may be portions of same chain folded back on itself or bonded
groups may be on separate chains.
Unorganized portions of protein
60% of the polypeptide chain in an average protein exists as helices and sheets.
The way that regions of secondary structure are oriented with respect to each other.
Tertiary structure predominates in globular proteins.
Monomeric proteins consist of a single polypeptide chain folded into its tertiary
structure.
Tertiary structure results from side chain interactions (Karp: p. 58 Fig. 2.35).
These are:
1. Hydrogen bonds
2. Hydrophobic bonds
3. Ionic bonds
4. Disulfide bond (Karp: p. 53)
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A compact shape.
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Capacity to do work.
Predict whether or not an input of energy is required to cause the event to happen.
2a 2) The Laws of Thermodynamics
First Law of Thermodynamics
2a 3) Free energy ( G)
1.
2.
3.
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Describes difference in free energy when one mole of each reactant is converted to
one mole of each product at 25C and 1 atm of pressure.
2.
3.
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ATP formation is coupled to the hydrolysis of phosphate compounds with a higher Go'.
e.g. glycolysis
2a 7) Utilization of free energy of ATP (Karp: p. 91-92 Fig. 3.6; Fig. 3.7)
1.
2.
3.
4.
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Reactants
1. Reactants bound by an enzyme are called substrates.
2. Substrates are converted to products.
3. Rate of a reaction is proportional to concentration of reactants.
4. All chemical reactions proceed toward a state of equilibrium.
5. At equilibrium, rates of forward and backward reactions are equal.
6. Ratio of products to reactants at equilibrium is an inherent property of reacting
chemicals.
7. The direction that the reaction is proceeding at any moment is dependent on relative
concentrations of all molecules at that moment.
Properties of enzymes
1.
2.
3.
4.
5.
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2b 2) Active site and Molecular Specificity (Figs. 3.10, 3.11, 3.12, 3.14)
Enzymes:
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Reversible inhibitors
A few hints.
Kinase usually involves ATP
e.g. hexokinase and pyruvate kinase
dehydrogenase usually involves coenzyme NADH
e.g. glyceraldehyde phosphate dehydrogenase
some exceptions to -ase ending
e.g. trypsin and pepsin
2b 6) Metabolic Regulation (Karp: pp. 112-116)
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Covalent modification (Karp: p. 112-113; p. 607 Fig 15.3; p. 619 Fig. 15.12)
1.
2.
3.
E1
E2
E3
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Catabolic pathways
Breaking of chemical bonds in large, complex molecules to form small simple molecules.
Require energy.
The two are interconnected.
Catabolic pathways provide energy and small molecules for anabolic pathways.
2c 2)Glycolysis (Karp: p. 108 Fig. 3.24)
1.
2.
3.
4.
5.
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Yields 2 NADH
a.
Fermentation
b. Electron transport chain in mitochondria
c.
Make NADPH
2c 3) Reducing Power
1.
2.
3.
4.
5.
6.
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Phosphofructokinase in glycolysis
fructose 6-phosphate + ATP ADP + fructose 1, 6-bisphosphate
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Nuclear envelope
Mitochondrial membranes
Chloroplast membranes
Lysosomal membrane
Endoplasmic reticulum
Summary of Membrane Functions
1. Compartmentalization
2. Provide a selectively permeable membrane
3. Transporting solutes
4. Responding to external signals
signal transduction
5. Intercellular interaction
6. Locus for biochemical activities
7. Energy transduction
3a2) Overview of plasma membrane structure
1.
2.
Biochemistry
a.
Consists of polar lipids arranged in a bilayer.
b. Proteins
c.
Carbohydrates
Appearance of plasma membrane in electron microscope
a.
Thin sectioning technique
~7.5 nm wide with dark, light, dark appearance (Karp: p. 118 Fig. 4.1)
b. Freeze fracture technique
Smooth areas interrupted by bumps and depressions. (Karp: p. 129 Fig. 4.15)
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3a 5) Membrane proteins
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1. Integral proteins
Integral membrane proteins are not totally free to drift in lipid sea.
Restraints as a result of:
a.
Interactions occurring within membrane.
b. Links to materials on inner or outer surface of membranes. (Karp: p. 142 Fig. 4.27)
Leads to membrane domains
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Highly polarized cells whose different surfaces carry out different functions.
1. Apical plasma membrane
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Tight Junctions (TJ): sealing extracellular space (Karp: p. 254 Fig. 7.30)
Gap junctions: mediate cell-to-cell communication (Karp: p. 257; Fig. 7.32; 7.33)
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2.
3b2) Diffusion
2.
3.
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2.
Passive diffusion
All driven by concentration gradient.
a.
Simple diffusion through lipid bilayer
b. Simple diffusion through an aqueous channel
c.
Facilitated diffusion solute binds specifically to a membrane protein carrier.
Active energy coupled transport
Greater the lipid solubility, faster the diffusion into the cell. (Karp: p. 145 Fig. 4.34)
Partition coefficient is a measure of lipid solubility or hydrophobicity or nonpolarity.
partition coefficient = concentration in oil
concentration in H2O
2.
3.
Ions and lager polar molecules, such as sugars and amino acids, cannot diffuse
through lipid bilayer.
Highly selective
Bidirectional.
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Secondary transport in intestine (Karp: p. 140 Fig. 4.30; p. 158 Fig. 4.49)
By convention, inside is negative with respect to outside (Fig. 4.51 & 4.52).
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Any molecules that happen to be present in enclosed fluid gain entry into
cells.
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High blood levels of LDL are associated with increased risk of heart disease.
(e.g.) atherosclerosis.
Atheroscleoris is characterized by LDL-containing plaques (atherosclerotic
plaques).
Plaques form on inner walls of blood vessels.
This causes the narrowing of major arteries and reduced blood flow.
Plaques also act as sites for formation of blood clots.
Blood clots that block coronary arteries are leading cause of myocardial infarction
(heart attack).
3.
Initiated by:
i.
Injury to endothelial cells lining blood vessels.
ii. Reactive oxygen species (ROS) chemically alter LDL-cholesterol.
Macrophages are attracted to injured endothelium and
i.
Ingest LDL oxidized by ROS.
ii. Accumulate cholesterol-rich fatty droplets in cytoplasm.
iii. Are referred to as macrophage foam cells.
Smooth muscle cells around blood vessel are:
i.
Stimulated to proliferate by foam cells and
ii. Produce fibrous cap that bulges into arterial lumen.
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High blood levels of HDL are associated with decreased risk of heart disease.
This is because HDL facilitates removal of cholesterol from blood.
Another factor is cholesteryl ester transfer protein (CETP).
CETP moves cholesterol from HDL to LDL.
Inhibiting CETP might elevate HDL and reduce coronary artery disease.
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2.
Fermentation
a.
In cytosol
b. Absence of O2
c.
d.
e.
3.
2-carbon acetyl group condenses with 4-carbon oxaloacetate to form 6-carbon citrate.
One turn of cycle evolves 2 CO2.
his completes oxidation of pyruvate.
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TCA or Krebs cycle: Central pathway of cell (Karp: p. 180 Fig. 5.8)
1.
2.
3.
Lipid-soluble molecule
4. Iron-sulfur proteins
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Proton-motive force
1.
2.
3.
4.
~220 mV
3d 6) ATP formation
1. Chemiosmotic mechanism
ATP
Each NADH = 3 ATP
Each FADH2 = 2 ATP
H2 O
Formed by O2 finally accepting electrons.
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= 6 ATP
= 18 ATP
= 2 GTP
= 36
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Autotrophs:
Utilize the radiant energy of sun to convert CO2 into organic compounds.
Photoautotrophs include
1.
2.
3.
4.
Higher plants
Eukaryotic algae
Various flagellated protists.
A variety of prokaryotes (e.g. green bacteria)
(CH2O) + O2
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3e2) Chloroplast
1. Organelle in which photosynthesis takes place.
2. Located predominantly in mesophyll cells of leafs.
3. Semi autonomous and self replicating.
4. Bound by 2 membranes separated by a narrow space.
5. Thylakoids flattened membranous sacs within chloroplast.
a.
Lumen space inside a thylakoid
b. Grana orderly stacks of thylakoids.
6. Stroma space surrounding thylakoids.
Overview of photosynthesis
light
6CO2 + 12 H2O C6H12O6 + 6O2 + 6H2O
2 series of reactions.
1.
2.
When a photon is absorb, compound is converted to a higher energy state (excited state).
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1.
2.
Photosystem II (PSII) (Karp: p. 215 Fig. 6.11 but not all details)
1.
2.
3.
4.
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Photosystem I (PSI) (Karp: p. 218 Fig. 6.15 but not all details)
3.
4.
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Remain in chloroplast.
a.
Regenerate RuBP
b. Converted to starch
Exported to cytosol.
a.
Converted to sucrose.
b. Oxidized in glycolysis and TCA cycle to provide ATP
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4e Cell cycle
4e1) Cell cycle defined
4e2) Macromolecular synthesis during the cell cycle
4e3) Cell Cycles in vivo
4e4) Control of cell cycle
4e5) Cyclin-dependent kinases (Cdks) and cell cycle control
4e6) Cell Cycle Check Points
4e7) M phase: Mitosis and Cytokinesis
4e8) Meiosis
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Mendel in 1860s.
A gene is a unit of heredity.
A gene is an element that controls a characteristic or a feature of an organism.
Mendel's laws describe behavior of these abstract units
Genes function by directing the synthesis of proteins. (Karp: p. 390 Fig 10. 11)
Beadle and Tatum 1940
One gene one enzyme hypothesis
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4a 6) Central dogma of molecular biology (Karp: p. 390; 421 Figs. 10.11; 11.2)
DNA
Transcription
mRNA
Translation
Protein
4a 7) Genetic code
Nucleotide combinations that specify placement of amino acids.
How many bases or nucleotides specify an amino acid?
1. If one base = one amino acid
2. If two bases = one amino acid we would have 16 words
42 = 16 code words are possible.
3. If three bases = one amino acid
43 = 64 code words are possible
Therefore, three bases = codon or code word.
Assigning code words
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Interphase nucleus
2.
Chromosomes
Genetically inactive.
i.
Constitutive heterochromatin
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DNA
Histones (Table 12.1, Karp: p. 481)
Highly conserved, basic proteins.
2.
A much tighter packing of chromatin that is achieved just prior to cell division.
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99 % do NOT move
However, a particular form of hemophila is caused by the insertion of a
retrotransposon into the gene that encodes a key blood-clotting enzyme.
4a14 Reversing the normal flow of genetic information: reverse transcription (Karp
p; 402-404)
1. defining step is use RNA as a template to synthesize DNA.
2. enzyme that carries out this is reverse transcriptase or RNA- dependent DNA
polymerase.
3. reverse transcription occurs in nature.
a. a small amount in animal cells
i. telomerase - an enzyme that maintains telomeres
-telomeres are repeated sequences that form a cap at each end of a
chromosome (Fig. 12.20 & unit 18 Karp 494).
- is a reverse transcription that has its own small amount of RNA.
ii. a few retrotransposons code for their own reverse transcriptase.
(Fig. 10.26)
b. retroviruses
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2.
3.
4.
5.
C
G
C
G
T
A
A
T
G
C
Termination region
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Makes mRNAs
Makes most small nuclear RNAs (snRNAs & snoRNAs) & microRNAs.
3. RNA polymerase III
S units depend on both size and shape and are not arithmetic.
e.g. eukaryotic ribosome is 80S and made up of a large (60S) and small (40S)
subunit.
2.
3.
4.
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RNAs are usually shortened and chemically modified after synthesis and before
use.
This usually occurs after transcription and is described as posttranscriptional processing.
Initial RNA is called primary transcript.
Final RNA is sometimes called mature RNA.
Many primary transcripts can be divided into two types of sequences:
1. Introns will be removed from primary transcript and often destroyed
2. Exons will be spliced together to form mature RNA
RNA processing occurs in tRNA, rRNA, and mRNA.
Will study mRNA (Karp p. 443 Fig 11.29)
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Initial or primary mRNA transcripts are often very large, have diverse base
sequence, and found only in nucleus.
These are heterogeneous nuclear RNAs (hnRNAs).
HnRNAs are precursors to mRNA.
Splicesosomes act on hnRNAs.
Splicesosomes contain snRNAs and proteins (ribonucleoprotein particles or snRNPs)
Some snRNAs are ribozmes.
Ribozmes are RNA catalysts that act on RNA to cut up RNA.
Splicesosomes cut and splice hnRNAs to yield final mRNAs.
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Their function is to recognize a mRNA codon and to position correct amino acid
into growing polypeptide.
Two important sites:
1. Amino acid attachment site. at 3' end.
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4b 9) Posttranslational modifications
1.
2.
3.
4.
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Experimental proof.
A somatic cell nucleus from a frog supports development of a frog if placed in the
appropriate cytoplasm cytoplasm of an unfertilized egg.
A similar experiment has now been done with mammals (Karp: p. 504, Fig. 12.31).
How is it that different types of cells in an animal or plant are able to synthesize
different proteins?
Enhancers
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2.
Certain proteins prevent mRNA from binding to ribosomes until after fertilization
b. microRNA (miRNA) (Karp 448-451; Fig 11.38 right hand side)
primary transcript of miRNA (pre-miRNA) fold backs on itself and is cleaved to
give double stranded miRNA.
associates with miRISC protein complex and is unwound into single strands.
this mature miRNA binds to a complementary region on a mRNA and inhibits
the translation of the mRNA.
3.
When down to 30 residues, mRNA rapidly degraded from 5' end. (Karp: p. 526
Fig. 12.56)
b. RNA interference (RNAi) by siRNA (Karp 448-451; Fig 11.38 left hand side)
Dicer, a particular type of ribonuclease, acts on dsRNA (e.g. RNA virus) to form
siRNAs.
siRNA associate with a protein complex (RISC) and a helicase unwinds the 2 RNA
strands.
The active, single-stranded siRNA associated with proteins of the RISC complex
binds to a mRNA target that has a complementary sequence.
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4c 9) Posttranslational control
1.
2.
3.
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80
A
C
A
G
G
However, 3 modes of DNA replication were possible. (Karp: p. 534 Fig. 13.1;
Fig. 13.2)
1. Conservative
2. Semi-conservative
3. Dispersive or random
old/old
new/new
old/new
new/old
2.
3.
4.
DNA polymerases
a.
DNA polymerase I (primer removal and fills in gaps)
b. DNA polymerase II (unknown)
c.
DNA polymerase III (replication)
RNA polymerases
a.
general one
b. specific one called a primase
DNA ligase
Topoisomerases
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3.
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RNA
Protein
4d 7) DNA repair (Karp: p 552-553)
Cells have tremendous potential for repair.
DNA is susceptible to environmental damage
Examples
1.
2.
3.
4.
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a.
If in gametes, next generation is affected.
b. If in somatic cells, cells can potentially become cancerous.
Impair transcription and replication and cause cell death
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2.
3.
Protein synthesis
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Regulation of Cdks
1.
2.
3.
4.
5.
Cyclin concentration
Cdk phosphorylation state (Fig. 14.6)
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Failure of checkpoints
1.
2.
A thin band (cortex) of contractile cytoplasm lies beneath the plasma membrane.
Cortex contains actin-myosin II filaments that interact to generate the force for
cytokinesis.
This is why you are unique and wonderful no matter how you do in cell biology.
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All that is transmitted across the membrane is a signal that the stimulus
(ligand) has been received.
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Receptors
Some examples
a.
Epinephrine receptor
b. EGF receptor
Effectors and 2nd messengers
Effectors
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2.
Receptor is not coupled to G-proteins but instead has tyrosine kinase activity.
Receptor Tyrosine Kinases (RTKs)
> 50 different RTKs have been identified (deal with in Unit 23)
5a 4) Interaction of heteromeric G protein with receptor and effector (Karp: p. 609, Fig. 15.4)
1.
2.
3.
4.
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Converts ATP into a second messenger product: cAMP (see section I below).
Phospholipase C (Karp p. 626, Fig. 15.7) (deal with in Unit 22)
Diacylglycerol (DAG)
5a 5) cAMP
PKA
7.
8.
9.
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b.
c.
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Many different stimuli induce their response in a target cell by causing a sudden
increase in the concentration of Ca++ in the cytosol.
Change can be:
i.
Oscillation
e.g. liver cells in response to vasopressin (Fig. 15.9)
ii. Elevation in a local region
e.g. macrophages undergoing phagocytosis
e.g. neurons (Fig. 15.25)
iii. A wave spreading from one end of cell to the other
e.g. egg upon fertilization (Fig. 15.27)
Opened by IP3
b. Ryanodine receptor (RyRs) in SER.
Found primarily in excitable cells.
can be opened by calcium itself.
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Examples of NO in medicine
1. Angina
2. Septic shock
3. Erections
1.
2.
3.
4.
5.
6.
7.
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b.
Tyrosine kinases are enzymes that add phosphates to specific tyrosine residues of
proteins.
Tyrosine kinases are involved primarily in control of cell proliferation and
differentiation (rather than intermediary metabolism)
Over 50 different RTKs have been identified.
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2.
3.
4.
Grb2:
i.
A specific SH2 protein. (Karp: p. 626 Fig. 15.17a; p. 629 Fig. 15.20)
ii. Functions as an adaptor protein.
iii. One domain binds to phosphorylated EGF receptor.
iv. Another domain binds to and activates Sos.
Sos:
i.
Is a GEF (help activate G proteins).
ii. Activates specifically a G protein called Ras.
Ras:
i.
A monomeric G protein
ii. Ras-GTP recruits another protein called Raf to plasma membrane.
Raf:
i.
A protein kinase
ii. At plasma membrane becomes activated protein kinase.
iii. Raf initiates MAP kinase cascade.
The MAP kinase cascade (mitogen-activated protein kinase) (Karp: p. 629 Fig. 15.20)
1.
2.
3.
4.
Inactivates MAPK
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Mobilizes glucose.
Caspases
Activated to caspases.
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2.
An endonuclease
3.
5c 8) Antiapoptotic mechanisms
1.
2.
3.
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Cells move to where they don't belong. (This is metastasis, next unit)
Tumor mass of cells
i.
Benign tumor cease to grow after reaching a certain size.
ii. Malignant tumor cells divide indefinitely and metastasize.
6a 2) Phenotype of a Cancer Cell
A.
Growth properties
1.
3.
4.
B.
1.
Normal cells stop moving when bump into neighbors but not tumor cells
Cancer cells often have abnormal chromosome numbers.
2.
3.
4.
6a 3) Causes of cancer
1. Chemical carcinogens
6a 4)Genetics of cancer
1. Cancer is monoclonal.
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3.
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Encode proteins that restrain cell growth and prevent cells from becoming
malignant.
Examples are Rb and p53.
Encode proteins that promote the loss of growth control and acquisition of
malignancy. (Karp: p. 686)
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f.
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Many cells secrete and organize materials into region beyond plasma membrane.
In multicellular animals, this is ECM.
ECM has two general functions.
a.
Support and protective material.
b. Permit expression of differentiated cell functions.
Epithelial tissue
1. Basal surface of epithelial tissues sits on basement membrane or basal lamina.
2. Basal lamina:
a.
Is 50 to 200 nm thick.
b. Acts as a barrier to passage of macromolecules.
c.
Is doubled layered in kidney.
B.
Connective tissue
e.g. cartilage, bone, tendons
ECM dominates and gives tissues identifiable properties.
e.g. collagen in tendons and proteoglycans in cartilage
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Protein-polysaccharide complex.
Consists of core protein to which chains of glycosaminoglycans (GAGs) are attached.
GAGs made up of repeating disaccharide in which two sugars are different.
GAGs are highly acidic due to sulfate and carboxyl groups attached to sugar rings.
Negative charges attract cations, which attract water.
Proteoglycans form a porous, hydrated gel that acts like 'packing material'.
b.
6b 5) Degradation of ECM
1.controlled ECM degradation is required for normal development & tissue
remodeling . e.g. formation of blood vessels -angiogenesis.
2.also involved in metastasis.
3.-accomplished largely by a family of zinc-containing enzymes, matrix
metalloproteinases (MMPs).
4.MMPs are either secreted or anchored to the plasma membrane.
5.cancer cells induce the synthesis and secretion of MMPs by the surrounding cells.
6.protein fragments of ECM act back on cancer cells to stimulate or inhibit their
growth & invasion.
6b 6) Integrins: the most important family of receptors that attach cells to ECM
(Karp: p. 240-241; Figs 7.13; 7.14)
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Focal adhesions
Hemidesmosomes
Focal adhesions or focal contacts are found in cells in culture dishes. (Fig. 7.17)
Scattered sites where cells come into close apposition (~10nm) to surface of dish.
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Are found in body between epithelial cells and underlying basement membrane.
Contain a dense plaque on inner surface of plasma membrane. (Karp: p. 244 Fig. 7.19)
Intermediate filaments (keratin) course out from the plaque.
Keratin filaments are linked to ECM by integrins.
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6b 10) Future
Trying to understand and treat cancer has led to tremendous gains in basic
knowledge about cells.
These have been triumphs of human intellectual endeavors.
Still treatments remain elusive for many cancers.
Numerous other diseases also have a cellular basis.
Thus many advances in basic cell biology can be expected in the future.
Some of these hopefully can be exploited for cures.
Your Ph.D. likely will involve cell biology.
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Which one of the following structures directly gives rise to a primary lysosome?
A. smooth endoplasmic reticulum
B. peroxisome
C. transition vesicle
D. phagosome
E. Golgi body or complex
2.
3.
Which one of the following sequences would be the correct RNA product from the
transcription of the following DNA sequences? ATCGCCAATATT
A. UAGTGGUUAUGG
B. ATCGCCAATATT
C. UAGCGGUUAUAA
D. URGCGGUURURR
E. none of the above
4.
5.
Receptor Tyrosine Kinases act as receptors for which one of the following ligands?
A. Low Density Lipoprotein (LDL)
B. insulin
C. epinephrine
D. adenylyl cyclase
E. none of the above
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113
Which one of the following pairs contains both a primary messenger and a
secondary messenger?
A.
B.
C.
D.
E.
7.
Which one of the following proteins is responsible for release of coated vesicles
from the membrane?
A. adaptin
B. histone
C. clathrin
D. dynamin
E. collagen
8.
Which one of the following words or phrases best completes the following statement?
In the Z pathway, H+ move from the ______________ to the ______________.
A. inner compartment of thylakoids; stroma.
B. outer chloroplast membrane; cytoplasm.
C. matrix; intermembrane space.
D. stroma; inner compartment of thylakoids.
E. matrix; stroma.
9.
If upon being placed in a solution a plant cell became turgid, what term would
describe the solution?
A. isotonic
B. isoosmotic
C. hypotonic
D. hypertonic
E. If none of the above are correct, answer e.
10. Which of the following completions best fills in the three blanks in the statement below?
A DNA sequence that directs the synthesis of _________________ or of a functional RNA
sequence is defined as a _________________ and would be known to ________________.
A. an enzyme; exon; Beadle and Tatum
B. a transcription factor; promoter; modern cell biologists
C. a polypeptide; gene; modern cell biologists
D. a polypeptide; intron; modern cell biologists
E. an enzyme; cistron; Mr. Bean
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E
A
C
E
B
D
D
D
C
C