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Biology Day 1 Biomolecules, Chemistry Review, Enzymes and Metabolism Carbohydrates

Monosaccharides glucose, fructose, galactose

Oligosaccharides sucrose (glu/fru), lactose (gal/glu), and maltose (glu/glu) are disaccharides

Polysaccharides starch, glycogen, cellulose, chitin, etc. Storage and structural polysaccharides

Starch glucose polymer functioning as energy storage in plants Glycogen glucose polymer functioning as energy storage in animals Cellulose glucose polymer functioning as a structural polysaccharide in plant cell walls

Chitin N-acetylglucosamine polymer functioning as a structural polysaccharide in insect exoskeletons and fungal cell walls

Proteins Amino Acids

-Polar (hydrophilic) vs nonpolar (hydrophobic) side chains

-Acidic vs. basic side chains

Asp and Glu are acidic (negatively charged at pH 7)

Lys and Arg are basic (positively charged at pH 7)

-some include His as basic (but not positively charged at pH 7)

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Lipids

Cholesterol

-Increases membrane fluidity at low temperatures

-Decreases membrane fluidity at high temperatures

-Steroid precursor

Triacylglycerols (triglycerides)

-3 fatty acids bonded to glycerol via ester linkages

Phospholipids

Lipid Bilayer

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Nucleic Acids

Bases

Purines (Adenine and Guanine) Pyrimidines (Cytosine, Uracil, Thymine)

Nucleoside (sugar + base) vs Nucleotide (sugar + base + phosphate)

Base-pairing (Watson-Crick)

Nucleoside

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Chemistry Review

Thermodynamics vs Kinetics

Thermodynamics

G = H - TS

G = G + RTlnQ

G = -RTlnKeq

Kinetics

Catalyst 1) Speeds up a reaction

2) Lowers the activation energy (in both directions)

3) Provides an alternate mechanism (pathway) for the reaction to occur

4) Is not consumed in a rxn

5) Does not shift the equilibrium.

Reaction Coordinate Diagrams

H S -TS

- + - Spontaneous at all temperatures

+ - + Non-spontaneous at all temperatures

- - + Spontaneous at low temperatures

+ + - Spontaneous at high temperatures

G1

G>0 Keq> 1 Products favored at eq.

K 0 Non-spontaneous (endergonic)

G = 0 Equilibrium

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Enzyme Kinetics

Michaelis-Menton Kinetics

Higher Km, lower affinity for substrate

Substrate Specificity

Feedback Inhibition

Competitive Inhibition

-Inhibitor binds to the active site

-Increases Km

-Does not change Vmax

Non-competitive Inhibition

-Inhibitor binds somewhere other than the active site

-Decreases Vmax

-Does not change Km

][

][max

SK

SVV

m

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Cooperativity

Sigmoidal curve

Hemoglobin vs. myoglobin

Bohr Effect - H+ and CO2 decrease the affinity of hemoglobin for O2

Enzyme Regulation

1) Allosteric Regulation (ex. feedback inhibition)

2) Phosphorylation (covalent modification)

-Ser, Thr, and Tyr residues can be phosphorylated by kinases (use ATP hydrolysis) or phophorylases

-Phosphatases dephosphorylate enzymes

-Phosphorylation can either activate or inhibit an enzyme depending upon the enzyme

3) Zymogens inactive precursors that become active upon proteolytic cleavage 4) Cofactors involvement of metal ions or organic molecules (coenzymes) 5) Association with other peptides

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Cellular Structure

Prokaryotes

-Single circular dsDNA genome and possibly the presence of a plasmid(s).

-No nucleus, membrane bound organelles or mitotic apparatus.

-Coupled transcription and translation.

Eukaryotes

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Organelle Function

Nucleus DNA storage and site of transcription

Surrounded by a nuclear envelope (2 lipid bilayers) through which nuclear pores regulate

traffic of large molecules

Contains the nucleolus (dark spot which is the site of rRNA synthesis)

Ribosomes Translation of mRNA into proteins (present in both pro- and eukaryotes)

Rough ER ER associated with ribosomes that is involved in synthesis and glycosylation of peptides to

form glycoproteins destined for secretion or integration into the membrane

Smooth ER Synthesis of lipids (membrane) and hormones often for export from the cell

Breakdown of toxins in liver cells

Golgi Apparatus Modification (glycosylation) and packaging of proteins into vesicles for secretion or transport to cellular destinations (like lysosomes)

Mitochondria Site of ATP synthesis via ATP Synthase as a result of oxidative phosphorylation (PDC,

Krebs cycle and the Electron Transport Chain)

Site of fatty acid catabolism (-oxidation) Have their own DNA (circular) and ribosomes for self-replication

Lysosomes Contains acid hydrolases (digestive enzymes) and have pH~5

Degradation of old organelles or phagocytosed materials

Produced from the Golgi Apparatus

Not present in plant cells

Peroxisomes Involved in the breakdown (involving hydrogen peroxide) of many substances including,

fatty acids, amino acids, and various toxins

Carry out the glyoxalate cycle in germinating plant seeds

Centrioles Source of the spindle apparatus used for cell division (acts as a microtubule organizing

center a.k.a. MTOC)

Not present in plant cells

Vacuoles Fluid-filled membrane-bound vesicles used for transport, storage of nutrients and other

substances, pumping excess water out of a cell, and cell rigidity (in plants)

Chloroplasts Site of photosynthesis in plant cells

Animal cells have lysosomes and centrioles (not present in plant cells).

Plant cells have cell walls, chloroplasts and a central vacuole (not present in animal cells).

Mitochondrial Structure

-PDC and Citric Acid Cycle occur in the matrix

-ETC Complexes are located in the inner membrane

-Protons are pumped (actively) from the matrix to the intermembrane space

-ATP synthase is located in the inner membrane and

synthesizes ATP on the matrix side

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Metabolism

Catabolism breakdown of molecules to release energy Anabolism construction of molecules (requires energy) Oxidation/Reduction

Catabolism of Glucose (oxidation of glucose):

C6H12O6 + 6O2 6CO2 + 6H2O

-Highly exergonic (G is negative)

Anaerobic Catabolism of Glucose

1) Glycolysis (cytosol) substrate-level phosphorylation 2) Fermentation (cytosol)

Glycolysis

-NAD

+ NADH (reduction)

-glucose 2 pyruvate (oxidation) -initial investment of 2 ATP followed by production of 4 ATP = net of 2 ATP

-formation of ATP here is referred to as substrate-level phosphorylation

Regulation: inhibited by ATP (feedback inhibition) and glucagon (low blood sugar hormone response)

activated by AMP, other reactants, and insulin (high blood sugar hormone response)

Fermentation

-occurs when aerobic respiration isnt possible -regenerates NAD

+ for more glycolysis

-NADH NAD+ (oxidation)

-pyruvate ethanol and CO2 pyr lactate (reductions)

Pyruvate CO2 + acetaldehyde ethanol (Alcohol Fermentation)

obligate anaerobe cant survive in the presence of O2; carry out only fermentation or anaerobic respiration facultative anaerobe capable of fermentation or aerobic respiration

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Aerobic Catabolism of Glucose 1) Glycolysis (cytosol) substrate-level phosphorylation 2) Pyruvate Dehydrogenase Complex (PDC) (Mitochondrial Matrix)

3) Citric Acid Cycle (also called Krebs Cycle or Tricarboxylic Acid Cycle) (Mitochondrial Matrix) 4) Electron Transport Chain (Mitochondrial Inner Membrane) oxidative phosphorylation

Pyruvate Dehydrogenase Complex (PDC)

-conversion of NAD

+ to NADH is a reduction

-conversion of pyruvate to acetyl-CoA and CO2 is an oxidation

Citric Acid Cycle

-net conversion of acetyl-CoA to 2 CO2 per cycle (which is an oxidation)

-conversion of NAD+ to NADH and FAD to FADH2 are reductions

-formation of ATP here is also referred to as substrate-level phosphorylation

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Electron Transport Chain

Chemiosmosis The electron transport chain establishes a proton gradient (establishing an electrochemical potential) which powers ATP synthase.

Summary of Aerobic Respiration

C6H12O6 + 6O2 6CO2 + 6H2O

Process Energy-Related Products ATP Yield

Glycolysis 2 ATP (net)

2 NADH

PDC 2 NADH

Citric Acid Cycle 2 ATP

6 NADH

2 FADH2

Totals 4 ATP

10 NADH (2.5-3ATP / NADH)

2 FADH2 (1.5-2ATP / FADH2)

4 ATP

25-30ATP

3-4 ATP

32-38ATP*

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Gluconeogenesis

Production of glucose; the reverse of glycolysis (uses a few different enzymes)

-occurs mainly in the liver (but also the kidneys)

Overall Regulation of Glucose Metabolism

Low ATP/ADP and NADH/NAD+ Ratios Catabolism activated and Anabolism inhibited

High ATP/ADP and NADH/NAD+ Ratios Anabolism activated and Catabolism inhibited

Glycogen Metabolism

Glucose polymer for glucose storage in the liver and muscles

-insulin (high blood sugar response) activates glycogen synthesis

-glucagon (low blood sugar response) and epinephrine (fight or flight) promote glycogenolysis (degradation)

Cori cycle lactate transported to the liver for conversion back to glucose

Lipid Catabolism (-Oxidation) -takes place in the mitochondrial matrix

-fatty acids are cleaved into 2 carbon fragments (acetyl-CoA)

-the acetyl-CoA can then enter the Citric Acid Cycle

-It costs two ATP to activate a fatty acid for -Oxidation

-Each round of -Oxidation produces 1 NADH and 1 FADH2

Protein Metabolism

Pyruvate, Oxaloacetate, and -ketoglutarate can be converted into various amino acids and vice-versa

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Biology Day 2 Molecular Biology: DNA and Protein Synthesis DNA and RNA

Nucleoside (ribose + base) vs. nucleotide (ribose + base + 3 phosphates)

Purines (guanine and adenine) and pyrimidines (cytosine, thymine, and uracil)

DNA double helix (right-handed helix)

Antiparallel strands

Complementary

Held together by H-bonding

Base stacking

Watson-Crick base pairing

G-C: 3 Hydrogen bonds

A-T: 2 Hydrogen bonds

Chromosome Organization

Prokaryotes - One circular chromosome (supercoiled by DNA gyrase)

Eukaryotes Many linear chromatin Wrapped around nucleosomes (histone octamers)

Chromatin are called chromosomes when condensed during mitosis

Have centromeres and telomeres

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Replication (Making DNA from a DNA template)

1) Helicase unwinds DNA helix and separates strands forming the replication fork(s) at the origin.

Topoisomerase unravels DNA ahead of the replication bubble to relieve tension.

2) Single-strand binding proteins bind and stabilize the single stranded DNA.

3) Primase lays RNA primers on the leading (only once) and lagging strand (many times).

4) DNA polymerase (III*) elongates new complementary strands for both the leading strand (continuously)

and the lagging strand (discontinuously) in the 5 3 direction (for both). The fragments on the lagging strand are called Okazaki fragments.

5) DNA ligase joins the Okazaki fragments together (seals the backbone).

6) DNA Polymerase (Pol I*) replaces the RNA primers with DNA

Semiconservative new DNA has one parent strand and one daughter strand

Replication of the telomeres (by telomerase) in eukaryotes

Energy provided by breaking high energy phosphate bonds during formation of phosphodiester linkages.

Reverse Transcriptase polymerase in retroviruses that synthesizes DNA from an RNA template

Prokaryotic DNA polymerases

DNA Pol Function Exonuclease Activity

DNA Pol I Replace Primers and DNA repair 3 to 5 and 5 to 3 exonuclease

DNA Pol II ??? SOS ??? ???

DNA Pol III Primary pol for elongation 3 to 5 exonuclease

Prokaryotes vs Eukaryotes

Prokaryotes Eukaryotes

1 Circular chromosome Many linear chromatin

Supercoiled (by DNA gyrase) Wrapped around nucleosomes (histone octamers)

1 origin of replication Many origins of replication

Bi-directional Bi-directional

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DNA Repair

Proofreading

35 exonuclease (Pol III) can remove the last nucleotide if an error occurs during replication.

Nick Translation

-Occurs when there is a nick in the DNA backbone

1) 53 exonuclease activity of DNA Pol I removes a few nucleotides from the 3 end at the nick 2) DNA Pol I then replaces the nucleotides it removed

3) DNA ligase seals the nick

Mismatch Repair

-DNA is methylated prior to replication (prokaryotes); this allows for the parent strand (methylated) and

daughter strand (not methylated) to be distinguished after replication and any errors during replication in the

daughter strand to be repaired.

-Several enzymes and proteins are involved.

1) The area around the mismatch is removed on the daughter strand.

2) DNA Pol III fills in the gap.

3) DNA ligase seals the backbone.

Base-excision Repair

1) A damaged base is removed leaving an AP site.

2) An AP endonuclease removes the rest of that nucleotide.

3) An exonuclease removes several more nucleotides.

4) DNA Pol I fills in the gap.

5) DNA ligase seals the backbone.

Nucleotide-excision Repair

-most common form of repair for damage caused by UV light.

1) The area around the damage is removed.

2) DNA Pol I fills in the gap.

3) DNA ligase seals the backbone.

Protein Synthesis

Prokaryotes

Eukaryotes

Transcription is the principle site for the regulation of gene expression (transcription factors).

Splicing introns, exons, spliceosomes, self-splicing, alternate splicing

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-Genetic Code is degenerate

Transcription (Making RNA from a DNA template)

1) Initiation - RNA Pol binds promoter region and begins unzipping DNA.

Promoter region contains a -35 sequence and Pribnow box in prokaryotes.

Promoter region often contains a TATA box in eukaryotes.

2) Elongation - RNA Pol begins transcribing (forming complementary RNA)

at the start site (5 3 direction). It is the template (or non-coding) strand only that is being transcribed.

3) Termination - Transcription is terminated at a special sequence.

Template Strand (Non-coding, anti-sense) vs. Coding Strand (Sense)

Gene a DNA sequence encoding for a protein (usually).

Prokaryotes Eukaryotes

1 RNA polymerase 3 RNA polymerases

(RNA pol I for rRNA nucleolus) (RNA pol II for mRNA)

(RNA pol III for tRNA)

Promoter is -35 sequence and

Pribnow box (-10)

Promoter is often TATA box (-25)

Occurs in the cytoplasm Occurs in the Nucleus

Coupled transcription/translation Not coupled (Occur in separate compartments)

No mRNA processing 5CAP, poly A tail, splicing out introns

mRNA is often polycistronic mRNA is monocistronic

Genetic Code

Start Codon

AUG

Stop Codons

UGA U Go Away UAA U Are Away UAG U Are Gone

Mutations

Point mutation a single base substitution Missense mutation point mutation leading to a codon coding for a different amino acid

Nonsense mutation point mutation leading to a stop codon Frame-shift mutation insertion or deletion leading to a change in the reading frame of a gene

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Lac Operon (an example of Transcription Regulation)

The Lac genes allow for the catabolism of lactose.

The repressor binds to the operator preventing transcription.

Lactose binds the repressor removing it from the operator.

Translation (Making a peptide from mRNA)

Initiation

1) Small ribosomal subunit binds to mRNA near the 5 end (along with many initiation factors). Shine-Dalgarno sequence at -10 in prokaryotes; other sequences in eukaryotes

2) Met-tRNA (fMet in prokaryotes) binds to the start codon (AUG) via its anticodon will be the P site. Aminoacyl site (A site), Peptidyl site (P site) and Exit site (E site)

3) Large ribosomal subunit binds.

Elongation

4) 2nd

charged tRNA binds at the A site (requires GTP hydrolysis).

5) Ribosome catalyzes peptide bond formation.

6) Translocation (APE) requires GTP hydrolysis.

Termination

7) release factor binds when stop codon appears in the A site.

-Charging tRNA requires ATP hydrolysis.

Ribosomes 70S (50S&30S) in prokaryotes and 80S (60S&40S) in eukaryotes)

Post-translational modifications may be made at the ER or Golgi body.

Replication Transcription Translation

Begins at Origin of Replication Start Site

(upstream promoter)

Start Codon(AUG)

(upstream Shine-Dalgarno sequence)

Elongation Enzyme DNA Polymerase RNA Polymerase Ribosome

Where? (prokaryotes) Cytoplasm Cytoplasm Cytoplasm

Where? (eukaryotes) Nucleus Nucleus Cytoplasm

Eukaryotic RNA polymerases

RNA pol I rRNA

RNA pol II mRNA

RNA pol III tRNA

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Recombinant DNA Techniques

PCR (Polymerase Chain Reaction) DNA amplification

1) Denaturation DNA strands are separated with heating (>90C)

2) Annealing The sample is cooled (~55C) to allow primers specific to the target sequence to anneal to the template strands of the target sequence.

3) Elongation Taq polymerase replicates the templates (~70C) 4) Thermal cycling is repeated many times.

Restriction Enzymes

-endonucleases that cut dsDNA at a specific sequence leaving either sticky or blunt ends.

-Eco RI cuts at the palindromic sequence 5' GAATTC 3'

Gene Cloning-Transferring a gene from one cell to another to impart the genes function

1) A gene is inserted into a plasmid using restriction enzymes and DNA ligase.

2) The plasmid is used to transform bacteria (bacteria take up the plasmid).

Plasmids small circular dsDNA that has an origin of replication, many restriction sites, and often antibiotic resistance and a promoter.

Can also be used in eukaryotes as well (needs eukaryotic promoter and poly A signal).

Hybridization

-DNA microarrays can be used to detect the presence/amount of specific DNA or RNA sequences

1) PCR (DNA with Taq polymerase; RNA with Reverse Transriptase)

2) DNA is denatured and single strands are allowed to anneal (when complementary) to single

stranded probe DNA on an array

3) A marker (often a fluorophore) allows for the detection and quantification of hybridized sequences.

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Biology Day 3 Microbiology Viruses

-Non-living, parasitic, infectious agent that can only replicate within a host cell.

-Viruses infect every type of living organism (plant, animal, bacteria, archaebacteria).

-Structure - nucleic acid encased in a protein capsid (enveloped and nonenveloped)

-Genome can be linear or circular and can be either dsDNA, ssDNA, dsRNA, or ssRNA.

-Relatively small genomes that can often be read in different reading frames.

-Typically uses hosts replication, transcription, and translation machinery. -Much smaller than prokaryotic or eukaryotic cells

Bacteriophage Life Cycles

Lytic Cycle

1) Adsorption Bind cell surface via tail (host cell specific interactions) 2) Penetration puncture cell wall and/or membrane and inject genome into the host cell 3) Hydrolase (a viral gene product) is produced and degrades the hosts genome. 4) Replication of the viral genome (many copies) and synthesis of much capsid protein

5) Assembly of new virus particles

6) Production of lysozyme to degrade the cell wall resulting in cell lysis and release of virus particles

Lysogenic Cycle

1) Adsorption Bind cell surface via tail (host cell specific interactions) 2) Penetration puncture cell wall and membrane and inject genome into the host cell 3) Integration of the phage genome into the host genome

4) Dormancy viral genes not expressed but are transmitted to all progeny during cell division 5) Activation excision of viral DNA and entrance into the lytic cycle

Eukaryote Viruses

-Animal cell viruses have similar cycles to the lytic and lysogenic.

-Viruses of eukaryotes often have a lipid bilayer envelope and enter the host cell via endocytosis and exit by

budding out of the host cell.

Host cells contain restriction enzymes that will degrade viral DNA. Bacteria methylate their own DNA to

distinguish it from foreign DNA.

Transduction transfer of genetic material via a virus in the lysogenic cycle.

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Virus Types (by genome) (Dont memorize all this but it should make sense to you)

[+] RNA viruses viral genome is ssRNA which can also serve directly as mRNA -must code for an RNA-dependent RNA polymerase for viral replication

[-] RNA viruses viral genome is ssRNA which is anti-sense (-) and therefore complementary to the mRNA coding for the viral genes.

Must code for an RNA-dependent RNA polymerase and include this polymerase in its capsid

to be infectious

Retroviruses [+] RNA viruses that convert their genomes into dsDNA for incorporation into the hosts genome; must encode an RNA-dependent DNA polymerase (reverse transcriptase)

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Prokaryotes

-Single circular dsDNA genome and possibly the presence of a plasmid(s).

-No nucleus, membrane bound organelles or mitotic apparatus.

-Coupled transcription and translation.

Eubacteria vs. Archaebacteria

Eubacteria (true bacteria) - include all of the typical bacteria including all of the bacterial pathogens -have peptidoglycan cell wall

Archaebacteria (ancient bacteria) - include the extremophiles -no peptidoglycan cell wall

-differences in transcription/translation machinery

-differences in membrane lipids

Classifications of Bacteria

Gram Positive Bacteria stain dark purple during gram staining -have cell membrane and cell wall (peptidoglycan)

Gram Negative Bacteria stain pink during gram staining -have cell membrane, cell wall and outer lipopolysaccharide (LPS) layer (contains endotoxins)

Flagellar Propulsion bacterial flagellum used by motile bacteria for locomotion Chemotaxis- movement is directed toward chemoattractants or away from chemorepellents

(sensed by chemoreceptors)

-powered by ATP hydrolysis

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Fission

Reproduction through 1) growth, 2) DNA replication, and 3) cell division.

Doubling times vary but can be as short as 20 minutes under ideal conditions.

Endospores dormant form produced by some bacteria under harsh conditions. -have a thick peptidoglycan coat and can survive through extreme conditions

Aerobes can survive in an oxygen environment Anaerobes do not require oxygen to survive Facultative Anaerobes can carry out out metabolic processes with or without oxygen Obligate Anaerobe cant survive in the presence of O2

Conjugation

-way to share genetic information adding to diversity

-common way of conferring antibiotic resistance genes

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Fungi

-Eukaryotes including yeast (unicellular) and a variety of multicellular forms

-Have a cell wall made of chitin

Asexual Reproduction

1) Budding - A fungal cell simply grows out of an existing fungal cell until distinct.

2) Spore Formation - produced by mitosis, spores will germinate under favorable conditions to become active.

Sexual Reproduction

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Eukaryotic Cells

-Animal cells have lysosomes and centrioles (not present in plant cells).

-Plant cells have cell walls, chloroplasts and a central vacuole (not present in animal cells).

Mitochondrial Structure

-PDC and Citric Acid Cycle occur in the matrix

-ETC complexes are located in the inner membrane

-Protons are pumped (actively) from the matrix to

the intermembrane space

-ATP synthase is located in the inner membrane and

synthesizes ATP on the matrix side

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Protein Trafficking

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Plasma Membrane

Fluid Mosaic Model Components free to move in 2D throughout the membrane -Composed of phoshpolipids, glycolipids and cholesterol

-Cholesterol adds rigidity to the membrane (at higher temperatures)

-Unsaturated fatty acids increase membrane fluidity

Hydrophobic molecules and small polar molecules (uncharged) can cross the membrane

(ex. CO2, O2, lipids (including certain hormones), some drugs)

Membrane Proteins

Peripheral membrane proteins adhere to membrane surface via electrostatic interactions

Integral membrane proteins anchored to and embedded in the membrane

Transmembrane proteins Spans the membrane and includes channel proteins, carrier proteins, porins

Cell Receptors - recognition glycoproteins on the cell surface that interact with hormones or other molecules

and relay signals into the cell

Adhesion proteins

Gap Junctions allow exchange of nutrients and cell-to-cell communication (ex. cardiac muscle cells)

Tight Junctions completely encircles cells and seals the space between them to prevent leakage -(ex. intestinal cells)

Desmosomes spot welds between cells that adhere them to one another and give mechanical strength -anchored to the cytoskeletons of each cell (ex. skin cells)

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Membrane Transport

Passive Transport

1) Simple Diffusion (ex. CO2, O2, lipids, some drugs)

2) Facilitated Diffusion diffusion of ions/polar solutes via a carrier protein (channel protein) (ex. glucose)

Active Transport - works against the concentration gradient and requires energy (ATP hydrolysis)

1) Primary (ex. Na/K pump 3Na+ pumped out and 2K+ pumped into cell; fueled by ATP hydrolysis) 2) Secondary uses one solutes gradient (established by ATP hydrolysis) to accomplish the transport of

another (Na+/glucose cotransport)

Cell Signaling and Second Messengers (G-Proteins)

1) Ligand binds G-protein receptor

2) G-protein receptor activates G-protein which binds GTP (exchanges GTP for GDP)

3) G-protein activates Adenylate Cyclase (ATP cAMP) 4) cAMP acts as a 2nd messenger activating a series of proteins and transcription factors

Osmosis

-plasmolysis vs. cytolysis

-hypertonic, hypotonic, isotonic

Exocytosis vs. endocytosis

Phagocytosis and pinocytosis

Receptor-mediated endocytosis

Cytoskeleton

Microtubules made from tubulin in a 9+2 arrangement -functions as a railroad for intracellular transport -found in the spindle apparatus of mitosis (MTOCs/centrioles), flagella, and cilia

Intermediate filaments support and maintain the shape of the cell

Microfilaments made from actin and involved in cellular motility, muscle contraction, and cytokinesis - ATP dependent myosin motors can move along actin

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Mitosis and the Cell Cy cle

Summary of the Cell Cycle

Cancer - unregulated or upregulated cell proliferation leading to tumor formation

Proto-oncogene normal gene that is often involved in regulating the cell cycle Oncogene mutated proto-oncogene that can lead to cancer (often in conjunction with other mutations)

-typically either mutated or have a significant increase in expression in tumor cells

-often prevent apoptosis in tumor cells

Tumor Suppressor Genes genes that regulate cell division, are involved in DNA repair, or promote apoptosis

Interphase

G1

S

G2

Protein/nucleic acid synthesis to prepare for replication; production of organelles

DNA Replication

Continued growth in preparation for mitosis

Prophase Chromosomes condense

Nuclear envelope disappears

Polarization of the centrioles (MTOCs)

Metaphase Chromosomes line up on metaphase plate

Spindle fibers attach at centromeres

Anaphase Spindle fibers pull sister chromatids apart towards the centrioles

Cleavage furrow begins forming

Telophase Nuclear membranes reform

Completion of cytokinesis

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Biology Day 4 Nervous and Endocrine Systems Neuron

Cell body (soma) contains nucleus and controls metabolic activity and biosynthesis Axon transmits impulses away from the cell body Dendrite receives signals and transmits it toward the cell body Myelin insulating sheath around axons (made by Schwann cells in the PNS and oligodendrocytes in the CNS) Nodes of Ranvier gaps in myelin sheath Synapse site of impulse propagation between cells (via neurotransmitters)

Action Potentials

-Resting membrane potential

-Na+/K

+ pump (active transport) and K

+ leak channels maintain resting potential

Refractory Period - Voltage-gated Na+ channels are inactivated until the resting potential is re-established

Propagation of action potentials

All or nothing principle strength of an action potential never varies -Intensity of a stimulus is related to the frequency of action potentials

Saltatory Conduction depolarization jumps to each successive node of Ranvier speeding up transmission

1) Depolarization (must exceed threshold of -50mV)

2) Voltage-gated Na+ channels open (further depolarization)

3) Voltage-gated Na+ channels close

4) Voltage-gated K+ channels open (repolarization/hyperpolarization)

5) Voltage-gated K+ channels close

6) Resting potential restored by Na+/K

+ pump

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Synaptic Transmission

Presynaptic Neuron

1) An action potential reaches the synaptic knobs

2) Voltage-gated Ca2+

channels open

3) Uptake of Ca2+

4) Exocytosis of neurotransmitter

Postsynaptic Cell

5) Neurotransmitter binds receptors

6) Ion channels open

7) Polarization is increased or decreased

8) Neurotransmitter activity is terminated

-diffuses away, degraded, or re-uptake

EPSP Excitatory postsynaptic potential IPSP Inhibitory postsynaptic potential

Neurotransmitter binding can be excitatory (EPSP) or inhibitory (IPSP). The additive effect of EPSPs and

IPSPs at all synapses determines whether an action potential is generated (summation).

Synaptic fatigue inhibition under constant or persistent stimulus; caused by depletion of synaptic vesicles

Neurotransmitters include acetylcholine, serotonin, dopamine, norepinephrine, epinephrine, GABA, and a few

amino acids and even gases

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Nervous System

Central Nervous System

-brain and spinal chord

-control and integration of body systems

Hindbrain

Cerebellum integration and control of complex motor functions

Pons maintaining balance; relay center between cerebellum and cerebral

cortex

Medulla (oblongata) controls some autonomic activity including heart

rate, respiration, digestive processes

Brainstem midbrain, pons, and medulla

Midbrain

Relay center for visual and auditory impulses

Forebrain

Telencephalon (cerebral cortex)

-divided into two hemispheres connected

by corpus callosum

-right hemisphere controls motor

functions for left side and vice versa

Diencephalon

-thalamus (sensory processing)

-hypothalamus (homeostasis; primary

control of endocrine system; primary link

between nervous/endocrine systems)

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Peripheral Nervous System

-All neurons outside the brain and spinal chord

-neurons are typically either afferent or efferent

Afferent sensory neurons that transmit to the CNS Efferent relay instructions from CNS to effectors (muscles and glands)

Somatic voluntary control of skeletal muscles Somatic motor neurons

-use acetylcholine as their neurotransmitter

-have cell bodies in the spinal chord or brain

Somatic sensory neurons

-have cell bodies in the dorsal root ganglion (just behind spinal chord)

-have long dendrite to cell body

-have axon that extends to spinal chord or brain stem

Autonomic involuntary control of smooth/cardiac muscles and endocrine/exocrine glands -important for maintaining homeostasis

-antagonistic control between sympathetic and parasympathetic

Autonomic Efferent Neurons

-there are two neurons connecting CNS to effector (preganglionic and postganglionic)

-postganglionic neuron has its cell body in an autonomic ganglion

-has an axon synapsing with the effector (smooth muscle or gland)

-the preganglionic neuron connects the CNS to the autonomic ganglion

-it synapses at the ganglion with the postganglionic neuron

-all preganglionic neurons use acetylcholine as their neurotransmitter

Sympathetic

-fight or flight -increase energy availability

-activated by stress

-nearly all postganglionic neurons use norepinephrine as their neurotransmitter

Parasympathetic

-rest and digest -store energy

-postganglionic neurons use acetylcholine as their neurotransmitter

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Sensory Reception

Types of receptors

1) Mechanoreceptors respond to mechanical disturbances 2) Chemical receptors respond to interaction with specific chemicals 3) Photoreceptors respond to light (electromagnetic radiation) 4) Thermoreceptors respond to changes in temperature 5) Pain receptors respond to tissue damage

Proprioceptors receptors giving self-awareness of relative positions of different body parts -largely integrated by the cerebellum

Olfaction and Taste

-the receptors involved are chemical receptors

Hearing

-the receptors involved are mechanoreceptors

1) Sound waves cause eardrum to vibrate.

2) Vibration is transmitted to and amplified by the three ossicles (malleus incus stapes). 3) Vibration is transmitted to the oval window.

4) Vibration of oval window causes pressure waves in the cochlear fluid.

5) Pressure waves cause basilar membrane to vibrate.

-The basilar membrane is coated with hair-like mechanoreceptors.

-Vibration of the basilar membrane disturbs the mechanoreceptors leading to an action potential.

Semicircular canals fluid-filled canals lined with hair-like mechanoreceptors that are important in maintaining balance

35

Vision

-the receptors involved are photoreceptors

1) Light passes through the cornea and enters the pupil.

2) Light then passes through the lens and is focused on the back of the retina.

-the retina contains rods (detect light) and cones (detect color)

3) Action potentials are generated in the rods and cones and transmitted to the optic nerve.

Iris muscle that regulates the diameter of the pupil to regulate the amount of light entering the eye

Optic disc area where the optic nerve connects to the eye -contains no photoreceptors

-responsible for the blind spot

36

Endocrine System

Nervous System vs. Endocrine System

Nervous System effects are fast-acting but short-lasting Endocrine System effects arent as fast-acting but are longer lasting

Endocrine vs. Exocrine

Endocrine Glands ductless glands that release hormones into the bloodstream that bind specific receptors on their target cells

Exocrine Glands glands that release their products via ducts either into the GI tract or outside the body

Types of Hormones

-Hormones from the brain are all peptides

-The only amino-acid derived hormones are epinephrine, T3, and T4

-All hormones from the adrenal cortex and the sex hormones are steroids

-testosterone, estrogen, progesterone, cortisol, aldosterone

Hormone Regulation

1) Nervous System hypothalamus controls anterior pituitary via neural pathways 2) Tropic Hormones hormones that control other hormones

Peptide (or Amino Acid derived) Steroid (derived from cholesterol) Water solubility hydrophilic hydrophobic

Synthesis Rough ER Smooth ER

Transport in Blood Free in plasma Protein-bound

Target Receptor Cell Surface Receptor Cytoplasmic Receptor

Mechanism 2nd

messenger Transcription Regulation

Duration of Effect Fast Acting / Short-lived Slow Acting / Long-lasting

37

HORMONES

GLAND HORMONE TARGET FUNCTION Hypothalamus tropic hormones Anterior Pituitary modify release of anterior pituitary hormones

Anterior Pituitary FSH (follicle stimulating hormone) ovaries/testes follicle development / spermatogenesis

LH (luteinizing hormone) ovaries/testes Ovulation / testosterone synthesis

ACTH (adrenocorticotropic hormone) adrenal cortex increase activity of adrenal cortex

TSH (thyroid stimularing hormone) thyroid increase TH

prolactin mammary glands milk production

GH (growth hormone) bone, muscle growth

Posterior Pituitary ADH (antidiuretic hormone, vasopressin) kidneys water retention

oxytocin mammary glands / uterus milk release / contraction

Pancreas glucagon (cells liver, muscles, adipose increase blood glucose

insulin (cells) liver, muscles, adipose decrease blood glucose

somatostatin (-cells) stomach, duodenum inhibit digestion

Thyroid T4 (thyroxin) generic increase metabolism

T3 (triiodothyronine) generic increase metabolism

calcitonin bone lower blood Ca2+

Parathyroid PTH (parathyroid hormone) bone increase blood Ca2+

Adrenal Medulla epinephrine heart, blood vessels, liver increase blood glucose and regulates blood circulation (fight or flight; rapid)

norepinephrine heart, blood vessels, liver increase blood glucose and regulates blood circulation (fight or flight; rapid)

Adrenal Cortex cortisol (glucocorticoids) generic increase blood glucose via protein catabolism (long-term stress response)

aldosterone (mineralocorticoids) kidneys increase blood pressure by reabsorption of Na+ and excretion of K

+

Kidneys erythropoietin bone marrow increase RBC synthesis

calcitriol bone increase blood Ca2+

Heart ANF (atrial natriuretic factor) kidneys lower blood pressure by increasing urination

Thymus thymosin thymus T cell development (childhood)

Testes testosterone testes / generic spermatogenesis / secondary sex characteristics

Ovaries estrogen uterus / generic menstrual cycle / secondary sex characteristics

progesterone uterus menstrual cycle, pregnancy

38

39

Biology Day 5 Circulatory, Lymphatic, and Immune Systems Circulatory System

FUNCTIONS OF THE CIRCULATORY SYSTEM

Delivers to Cells Removes for Excretion Distributes O2 (from lungs) CO2 (to lungs) Immune cells/antibodies

Nutrients, Ions, H2O (from intestines/liver) Ammonia/Urea and H2O (to kidneys) Clotting factors

Signal molecules (from endocrine glands) Heat (to skin)

Flow P/R Pressure decreases over distance

Cardiac Output = (Stroke Volume)(Heart Rate) CO = (SV)(HR)

Heart

Diastole Systole 1) Atria contract 1) Ventricles contract

2) Ventricles fill from atria 2) AV valves close (lub)

3) Semilunar valves open

4) Blood flows into aorta / pulmonary artery

5) Semilunar valves close (dub)

Atrioventricular valves

tricuspid (right)

bicuspid (left)

-(i.e. mitral valve)

Semilunar valves

pulmonary valve

aortic valve

40

Cardiac Conduction

1) An action potencial (AP) is first produced in the SA node (SinoAtrial node)

-Contractions arent initiated by the nervous system 2) The AP spreads through the atrial cardiac cells through gap junctions

3) The AP spreads to the AV node (AtrioVentricular node) through special conduction fibers (small delay here)

4) The AP is spread through the Bundle of His and Purkinje fibers to the ventricles

5) The AP spreads through the ventricular cardiac cell through gap junctions

Heart Regulation

1) Sympathetic nervous system (vagus nerve)

2) Adrenal Medulla (epinephrine/norepinephrine)

Arteries

-carry blood (usually oxygenated) away from the heart

-high pressure

-lined with smooth muscle (can constrict/relax to regulate flow)

Veins

-carry blood (usually deoxygenated) toward the heart

-very low pressure

-valves prevent backflow

-larger veins are lined with some smooth muscle

Capillaries

-very narrow blood vessels; wide enough for a single RBC to pass through

-where gas/nutrient/waste exchange takes place

Portal Circulation

-circulation between capillary beds

Hypophyseal Portal System hypothalamus to pituitary gland Hepatic Portal System from small intestine to liver

41

Capillary Exchange

-O2 and CO2 can diffuse across the cell membrane

-capillaries are thin (1-cell thick) and porous

-nutrients can pass through the pores

-WBCs and pathogens can pass through the pores

-water can also pass through the pores

Exchange of Water

Arteriolar End

-high hydrostatic pressure

-high tissue osmolarity

-water is forced out

Venular End

-lower hydrostatic pressure

-increased blood osmolarity (oncotic pressure)

-water is forced back in

Blood Composition

Erythrocytes

Red Blood Cells or RBCs

-produced in the bone marrow

-no nucleus (short-lived)

-aged RBCs filtered by spleen

-contain lots of hemoglobin

-transport O2 to the tissues

-transport CO2 to the lungs

hematocrit = % RBCs

Leukocytes

-mediators of the immune system

Plasma

-mostly water

-proteins (ex. albumin)

-ions

-dissolved O2 and CO2

-volume regulated by kidneys

Clotting Factors

-Platelets produced in the bone marrow

-Fibrinogen/clotting proteins made in liver

1) Vasoconstriction (paracrine-induced)

2) Tissue damage attracts platelets (forms platelet plug)

3) Tissue damage sets off a coagulation cascade

-end result is conversion of fibrinogen to fibrin

-clot is composed mostly of platelets and fibrin

42

Hemoglobin

-each hemoglobin can bind up to four O2 -cooperative binding of O2 -Sigmoidal binding curve

-hemoglobin vs. myoglobin

Bohr Effect - H+ and CO2 decrease the affinity of hemoglobin for O2

(right shift of the curve)

CO2 + H2O H2CO3 H+ + HCO3

43

Lymphatic System

1) returns plasma lost at the capillaries to the circulatory system

-fluid flow is unidirectional and the lymph is emptied into the venous circulation via the thoracic duct

2) lymph nodes serve as a reservoirs of macrophages, B cells, and T cells

-pathogens are often first encountered by the immune system in the lymph nodes

-immune responses are often first initiated in the lymph nodes

3) larger glycerides are absorbed directly into the lymph system from the small intestine

-they are emptied into the circulatory system via the thoracic duct

spleen - has a reservoir of macrophages and immune responses are often initiated here also

44

Immune System

Leukocytes (White Blood Cells) mediate the immune system macrophages and neutrophils - phagocytes

mast cells and basophils secrete histamine; mediate the inflammatory response and allergic reactions lymphocytes (B cells, T cells, NK cells)

eosinophils destroy multi-cellular parasites; mediate allergic reactions

Innate Immunity

1) Epithelial tissues form a barrier (skin, lining of GI tract and respiratory tract)

2) tears and saliva contain lysozyme; stomach pH ~ 2)

3) Phagocytes ingest foreign material (macrophages and neutrophils)

4) Complement system system of proteins effecting lysis of pathogens or virus-infected cells

Inflammatory Response

Purpose

1) Attracts immune cells

2) Produces a physical barrier (reduces the spread of infection)

3) Promotes tissue repair

Process

1) Activated macrophages release cytokines which attract other immune cells to the site

2) Attracted immune cells release their cytokines

Cytokines Released

Interleukins mediate the inflammatory response and cause fever Histamine vasodilation and increases capillary permeability (released by mast cells and basophils) Heparin anticoagulant

Natural Killer (NK) Cells

-Recognize virus-infected cells and induce apoptosis

45

Humoral Immunity

-mediated by antibodies (immunoglobulins)

-variable (VDJ) recombination produces antibodies for any antigen

-antibody binding tags an antigen for phagocytosis and activates the complement system

-antibodies are expressed on the surface of B cells

-B cells are produced in the bone marrow

-B cells recognizing self-antigens are eliminated in the bone marrow (maturation)

-B cells are also Antigen Presenting Cells and can activate Th cells

Primary Humoral Response

-1st exposure to a pathogen

-Antigen recognition activates a naive B cell

-Naive B cell proliferates (clonal selection)

-Memory cells and plasma cells are produced

-Plasma cells secrete antibodies

-takes 5-7 days

Secondary Humoral Response

-2nd exposure to a pathogen

-memory cell response is much faster

46

Cell-Mediated Immunity

-mediated by Helper T cells and Cytotoxic T cells

-T cells are produced in the bone marrow

-T cells recognizing self-antigens are eliminated in the thymus (maturation)

-Helper T cells (Th) secrete cytokines activating many types of immune cells

-recognize MHC II bound antigen by an Antigen Presenting Cell (APC)

-Cytotoxic T cells (Tc) induce apoptosis of tumor cells or virus-infected cells

-recognize MHC I bound antigen by any nucleated cell

Antigen Presenting Cell (APC) present antigen on MHC receptor -MHC II recognized by Th cells as they are CD4+ (macrophages, B cells, dendritic cells)

-MHC I recognized by Tc cells as they are CD8+ (most any cell)

Dendritic Cell APC found in epithelial tissues -once antigen is bound they migrate to lymph nodes to present to T cells

47

Biology Day 6 Digestive and Excretory Systems Digestive System Alimentary Canal (GI Tract)

-canal from mouth to anus

Ingestion

-mastication breaks up food into smaller pieces

-saliva lubricates food and contains enzymes

amylase converts starch to disaccharides lipase fat digestion (minimal) lysozyme anti-bacterial

-the epiglottis prevents food/liquids from entering the trachea as it passes from the mouth through the pharynx

to the esophagus

-the esophagus is lined in smooth muscle which propels food to the stomach (peristalsis)

48

Stomach

Partial Digestion

1) pH ~ 2 partial hydrolysis of proteins and carbohydrates -HCl secreted by parietal cells

2) pepsin also functions in proteolysis

-produced and secreted as a zymogen (pepsinogen) by chief cells

-converted to active form by acid-catalyzed proteolysis in the stomach

3) gastric smooth muscle churns food (mixing) aiding in digestion

Regulation

1) gastrin secreted by G cells stimulates secretion of HCl and pepsinogen

2) histamine stimulates secretion of HCl

3) stimulated by parasympathetic nervous system (inhibited by sympathetic)

-the cardiac sphincter prevents stomach reflux into the esophagus

-the pyloric sphincter regulates passage of food/liquids to the small intestine

-the pyloric sphincter is controlled by the enteric nervous system

-the pyloric sphincter also closes in response to cholecystokinin (endocrine control)

Liver

1) Produces bile from cholesterol

-bile aids in digestion of lipids (emulsification; increases exposed surface area)

-bile facilitates absorption of fat-soluble vitamins

-bile is stored in the gall bladder

-bile is delivered to the duodenum via the common bile duct

-bile is reabsorbed in the ileum

2) Regulation of blood glucose

- insulin stimulates glycogen synthesis (lowers blood sugar)

- glucagon, epinephrine, cortisol stimulate glycogenolysis / gluconeogenesis (raises blood sugar)

3) Cori Cycle

-lactate produced in muscles is converted back into pyruvate and ultimately glucose in the liver

4) Lipid metabolism

-production of lipoproteins (from chylomicrons)

-lipoproteins distribute cholesterol and triglycerides to the tissues

5) Conversion of NH3 to urea (from amino acid catabolism)

6) Detoxification

-drugs/toxins are converted to less harmful substances

7) Storage of Fat-soluble Vitamins

-stores vitamins A, D, E, K (along with adipose tissue)

8) Production of Plasma Proteins

-albumin, fibrinogen, other clotting factors

49

Pancreas

1) Produces Digestive Enzymes (Exocrine)

amylase converts polysaccharides to disaccharides protease zymogens

trypsinogen activated by enterokinase in the duodenum chymotrypsinogen activated by cleavage by trypsin in the duodenum procarboxypeptidase activated by enteropeptidase in the duodenum

lipase converts triglycerides to fatty acids and monoglycerides nucleases hydrolyze nucleic acids

-enzyme secretion stimulated by cholecystokinin (from duodenum)

-delivered to the duodenum via the pancreatic duct

2) Secretion of Bicarbonate (Exocrine)

-keeps pH in duodenum slightly basic

-secretion stimulated by secretin (from duodenum)

-delivered to the duodenum via the pancreatic duct

3) Produces Hormones (Endocrine)

-hormones produced by cells in regions called Islets of Langerhans

glucagon is secreted by cells (raises blood sugar) -stimulates glycogenolysis / gluconeogenesis by the liver

-stimulates release of fats into the blood stream by adipocytes

insulin is secreted by cells (lowers blood sugar) -stimulates glycogen synthesis by liver and skeletal muscle

-stimulates glucose uptake by skeletal muscle and adipose tissue

somatostatin secreted by cells -inhibits HCl secretion by parietal cells

-inhibits secretion of gastrin, histamine, secretin, and cholecystokinin

Small Intestine (duodenum, jejunim, and ileum)

Duodenum site of most digestion and absorption Jejunum / Ileum specialized absorption Brush border cells microvilli-covered regions of the lumen of the small intestine

50

Small Intestine (continued)

1) Digestion

Carbohydrates

Pancreatic amylase converts polysaccharides into disaccharides

Brush border enzymes convert disaccharides into monosaccharides

Proteins

Pancreatic proteases convert peptides to di- and tri-peptides

Brush border proteases convert di- and tri-peptides to amino acids

Fats

Bile emulsifies fat droplets into smaller micelles

Lipases convert triglycerides to fatty acids and monoglycerides

2) Absorption

Carbohydrates

Monosaccharides enter epithelial cells via symport with Na+ (2 active transport)

They exit epithelial cells via facilitated diffusion and are taken up by the capillaries

Proteins

Amino acids enter epithelial cells via symport with Na+ (2 active transport)

They exit epithelial cells via facilitated diffusion and are taken up by the capillaries

Fats

a) Fatty acids and monoglycerides diffuse into epithelial cells

b) Theyre converted back into triglycerides and packaged into chylomicrons c) Chylomicrons exit epithelial cells into lacteals of the lymphatic system

d) The lymphatic system empties into the venous circulation at the thoracic duct

3) Enzyme Production (Exocrine)

Enterokinase conversion of trypsinogen to trypsin -trypsin activates other proteases

Brush border enzymes responsible for final digestion of disaccharides and peptides before absorption

4) Hormone Secretion (Endocrine)

cholecystokinin secreted due to presence of food and causes pancreas to release digestive enzymes secretin secreted due to presence of acid and causes pancreas to release bicarbonate into the duodenum

Large Intestine (cecum, colon, and rectum)

1) Absorption of water, electrolytes, and vitamins

-there are hundreds of species of bacteria in the colon

-they most notably produce vitamin K and biotin (vitamin B7)

-they also produce GAS

2) Formation of feces (compaction)

3) Storage of feces in the rectum

51

Excretory System

Functions

1) Regulation of extracellular fluid volume and blood pressure

2) Regulation of osmolarity

3) Homeostasis of acid-base balance (either HCO3- or H

+ can be excreted)

4) Excretion of wastes (including urea and uric acid)

5) Homeostasis of ion balance

6) Regulate red blood cell synthesis (secretion of erythropoietin)

52

Urine Formation

1) Filtration hydrostatic pressure forces plasma from the capillaries of the glomerulus into the lumen of Bowmans Capsule of the nephrons 2) Reabsorption much of the filtrate is recovered from the nephron tubule into the peritubular capillaries

-H2O, ions, glucose, amino acids, proteins, and urea are reabsorbed

-most reabsorption takes place in the proximal convoluted tubule

3) Secretion certain solutes are concentrated in the urine from the peritubular capillaries -most secretion takes place in the distal nephron (distal convoluted tubule and collecting duct)

-K+, H

+, and organic molecules (including drugs and toxins) are added to the filtrate

ADH (vasopressin) released by the pituitary gland in response to low blood volume / high blood osmolarity -increases water reabsorption by the distal nephron

Aldosterone released by the adrenal cortex in response to low blood pressure -increases Na

+ reabsorption by the distal nephron (results in increased water retention and thirst)

The Loop of Henle is a countercurrent multiplier.

53

Biology Day 7 Muscle and Skeletal Systems Muscle System

Skeletal Muscle

Functions

1) Support and mobility (locomotion)

2) Peripheral circulation

3) Thermoregulation (shivering) - simultaneous stimulation of antagonistic pairs of skeletal muscles by the SNS

SKELETAL CARDIAC SMOOTH

Striated (sarcomeres) Striated (sarcomeres) Not striated (no sarcomeres)

Voluntary Involuntary Involuntary

Skeletal system Heart Hollow organs, tubes, sphincters

Multi-nucleated Uni-nucleated Uni-nucleated

No gap junctions Gap junctions Gap junctions

Somatic motor neurons Autorhythmic cells Autonomic motor neurons

Regulated by Ca2+

(SR)

Troponin / tropomyosin

Regulated by Ca2+

(SR)

Troponin / tropomyosin

Regulated by Ca2+

(extracellular & SR)

calmodulin / MLCK

Fastest contractions Intermediate contractions Slowest contractions

Muscle Cell Vocabulary

muscle fiber = muscle cell

sarcolemma = cell membrane

sarcoplasm = cytoplasm

sarcoplasmic reticulum (SR) = modified ER

54

-Each neuron may innervate multiple muscle fibers.

-But each muscle fiber will be innervated by a single neuron.

-Increased muscle tension is accomplished by:

1) Increased recruitment of motor units (more motor neurons and their muscle fibers)

2) Increased frequency of stimulation

Sliding Filament Theory

Thin (myosin) and thick (actin) filaments slide past each other during contraction.

55

Muscle Twitch (Contraction and Relaxation)

Contraction

1) Acetylcholine (Ach) is released by a somatic motor neuron.

2) Ach binds Ach receptors / Na+ channels on the muscle fiber (influx of Na

+).

3) Depolarization above the threshold opens voltage-gated Na+ channels and initiates an action potential (AP).

6) Voltage-gated Ca2+

channels open in the sarcoplasmic reticulum (Ca2+

is normally sequestered in the SR).

7) Ca2+

binds to troponin (which is bound to tropomyosin).

8) Troponin removes tropomyosin off of the myosin-binding sites of actin.

9) The myosin powerstroke ensues.

Relaxation

10) Ca2+

is actively pumped back into the sarcoplasmic reticulum.

11) Troponin releases Ca2+

.

12) Tropomyosin binds to the myosin-binding sites of actin.

Action of Myosin

1) Binding of ATP myosin releases actin 2) ATP hydrolysis myosin reattaches to actin (forms crossbridge closer to the center of the sarcomere) 3) Power stroke (Pi is released) myosin pulls actin toward the center of the sarcomere 4) ADP is released myosin is now tightly bound to actin (rigor)

Energy Consumption

-Active skeletal muscles have a huge demand for ATP

-Creatine phosphate can replenish some ATP

-donates a high energy phosphate to ADP

-Muscles store glycogen for rapid utilization of glucose

-Aerobic respiration produces lots of ATP (requires lots of O2)

-myoglobin stores O2 in muscle and releases it as needed

-During prolonged contraction, lactic acid fermentation is more common

-insufficient O2 for aerobic respiration

-aerobic respiration is too slow to meet the demand

-lactic acid fermentation produces ATP quickly (2 ATP net per glucose)

-lactate must be shuttled to the liver to be converted back to pyruvate (Cori Cycle)

56

Skeletal System

Endoskeleton vs Exoskeleton

Funtions

1) Structural rigidity and support

2) Calcium storage

3) Protection of organs

4) Hematopoiesis red bone marrow synthesizes RBCs, WBCs, and platelets

Human Skeletal System

Axial Skeleton head and trunk (skull, spinal column, sternum, ribcage, etc.) Appendicular Skeleton everything else

Bone Types

1) Flat bones (pelvis, sternum, skull, etc.)

-protect vital organs

-spongy bone surrounded by layer of compact bone

-contain red marrow (hematopoiesis)

2) Long bones (arms and legs)

-support and mobility

-epiphyses contain spongy bone (red marrow - hematopoiesis) surrounded by a layer of compact bone

-epiphyses are coated with articular cartilage

-diaphysis (central shaft) is a tube of compact bone with yellow marrow and blood vessels inside

-epiphyseal plate is the site of bone growth in children / adolescents

57

Joints

1) Synarthrosis dont allow movement ex) skull

2) Amphiarthrosis allow limited movement ex) intervertebral disks

3) Diarthrosis (synovial) freely movable joint Gliding carpals of the wrist Hinge elbow Saddle - thumb

Ball and Socket shoulders and hips

Arthritis Inflammation of a joint -can lead to destruction of the articular cartilage

Cartilage

Extracellular tissue secreted by chondroblasts / chondrocytes

-composed of a matrix of collagen and elastin fibers with proteoglycans interspersed

-avascular and not innervated

Types

1) Hyaline strong, flexible ex) nose, ears, trachea, ribs, synovial joints (articular cartilage)

2) Fibro strong, rigid ex) intervertebral disks

3) Elastic Strong, flexible ex) ear lobes, epiglottis, larynx

Ligaments and Tendons

Ligaments connective tissue connecting bone to bone Tendons connective tissue connecting muscle to bone

58

Bone Structure

Extracellular tissue composed of a matrix of collagen with calcium phosphate (hydroxyapatite) interspersed

-produced by osteoblasts from calcified cartilage

-vascular and innervated

-the osteon is the fundamental unit of compact bone

Osteocyte mature osteoblast trapped in lacunae in between layers of lamellae in the osteon Osteoclast cells responsible for reabsorbing Ca2+ from bones

Hormonal Regulation of Bone Growth / Remodeling

1) Calcitriol (vitamin D3) raises plasma [Ca2+

]

-enhances intestinal absorption of Ca2+

-stimulates osteoclasts (Ca2+

reabsorption)

-facilitates renal reabsorption of Ca2+

2) Parathyroid Hormone (PTH) - raises plasma [Ca2+

]

-stimulates osteoclasts

-enhances renal reabsorption of Ca2+

-increases production of calcitriol

3) Calcitonin decreases plasma [Ca2+] -inhibits osteoclasts

-increases renal secretion of Ca2+

59

Biology Day 8 Respiratory and Skin Systems Respiratory System

Functions

1) Gas Exchange

-exchange of O2 / CO2 by the alveoli

2) pH Regulation

-removal of CO2 reduces acidity

-hyperventilation reduces acidity (increases pH)

-hypoventilation increases acidity (decreases pH)

3) Thermoregulation

-significant amount heat is lost to expired air

4) Protection from pathogens and particulates

-nose hairs and mucous prevent pathogens / particulates from reaching the lungs

-goblet cells secrete mucus lining the respiratory tract

-cilia propel mucus and pathogens / particulates trapped in it toward the throat

-macrophages in the alveoli phagocytose pathogens / particulates

Structure

60

1) Conducting System air passages leading to alveoli

mouth/nose nasal cavity pharynx larynx trachea primary bronchi bronchi bronchioles

2) Exchange Surface bronchioles / alveoli

3) Associated muscles, bones, etc. of the thoracic cavity

-diaphragm, abdominal muscles, intercostals, rib cage, etc.

Alveolar Structure

-air-filled sacs in the lungs that are surrounded by capillaries

-thin walled with a huge surface area (maximizes gas exchange)

-coated in surfactant (reduces surface tension keeping alveoli from collapsing)

Type I alveolar cells make up 95% of alveolar walls and is the site of gas exchange Type II alveolar cells secrete surfactant

Ventilation

Inspiration is caused by contraction of the diaphragm (a skeletal muscle)

-the lungs are surrounded to two pleural sacs

-a small layer of fluid fills the space between inner and outer pleural sacs

-the diaphragm is connected to the outer pleural sac

-expansion of the lungs lowers the pressure inside them

-the diaphragm is innervated by the Somatic Nervous System (like all skeletal muscle)

-inspiration can be both voluntary and involuntary (controlled by the medulla)

Expiration is usually passive elastic recoil of the lungs (resiliency)

-forced expiration involves contraction of the abdominal and intercostal muscles

Regulation

-low plasma O2 or high plasma CO2 result in increased ventilation

-low plasma pH results in increased ventilation

61

Skin

Functions

1) Prevent Loss of H2O relatively impermeable to H2O

2) Thermoregulation

Heat Retention

i) hairs help with heat retention (arrector pilimotor muscle extends hair when cold)

ii) hypodermis contains an insulating layer of adipose tissue to prevent heat loss

iii) vasoconstriction of the surface capillaries in the dermis minimizes heat loss

Heat Removal

i) sweat glands in the dermis release sweat (mostly water / salt) evaporation removes heat -too little or excessive sweating can affect osmoregulation

i) vasodilation of the surface capillaries in the dermis increases heat lost through the skin

3) Physical Protection

-skin is a layer of protection from pathogens

-fingernails / toenails (made of keratin) protect the tips of fingers and toes

-callus build up protects areas more prone to abrasion

Dermal Layers

1) Epidermis composed of stratified squamous epithelial cells -cells in the deepest epidermis are constantly dividing and being pushed towards the surface

-dead cells at the surface leave behind a network of keratin and phospholipids which waterproof the skin

2) Dermis composed of loose connective tissue; contains blood vessels, nerve endings and exocrine glands

3) Hypodermis contains adipose tissue for insulation

62

Biology Day 9 Reproductive Systems and Development Reproductive Systems

Male Reproductive System

Gonads testes; produce sperm and secrete testosterone External genitalia penis and scrotum (sac holding testes helps regulate temperature) Internal genitalia accessory glands and ducts

63

Female Reproductive System

Gonads ovaries; produce ova and secrete estrogen and progesterone External genitalia vulva (labia majora and minora, clitoris) Internal genitalia vagina, uterus, fallopian tubes

Vagina birth canal

Uterus the womb Endometrium layer of glandular epithelium shed during menstruation Myometrium thick layer of smooth muscle

Cervix opening of the uterus -dilated slightly during fertile days and greatly during childbirth

Fallopian Tubes carry ova from the ovary to the uterus (via peristalsis)

Gametogenesis

MALE FEMALE

GONADS testis ovaries

GAMETES spermatozoa ova

GERM CELLS spermatogonia oogonia

RESULT 4 haploid sperm 1 ovum, 2 polar bodies

WHEN Daily beginning at puberty ~500,000 primary oocytes produced

during fetal development;

ovulation from puberty to menopause

64

Spermatogenesis

-Spermatozoa are produced in the seminiferous tubules of the testes

-Sustentacular cells regulate sperm development (provide sustenance) -Leydig Cells (Interstitial Cells) secrete testosterone

GnRH stimulates release of LH and FSH

-LH and FSH inhibit GnRH (negative feedback)

LH stimulates Leydig cells to produce testosterone

-testosterone needed to maintain spermatogenesis

FSH stimulates sustentacular cells

-initiates and maintains spermatogenesis

Testosterone inhibits release of GnRH and LH

Testis also release inhibin

-inhibits release of FSH

65

Oogenesis

-oogonia develop into primary oocytes before birth

-primary oocyte splits into a secondary oocyte and first polar body in Meiosis I

-Meiosis II is only completed if an ovum is fertilized

66

Ovarian Cycle

-Each primary oocyte is enclosed in a follicle

-Oocyte is surrounded by a layer of granulosa cells and an outer layer called the theca

Follicular Phase (Days 1-13) FSH stimulates follicle maturation -FSH and LH stimulate production of estrogen by the maturing follicle

Ovulation (Day 14) a spike in LH results in release of a secondary oocyte -the follicular remains becomes the corpus luteum

Luteal Phase (Days 15-28) the corpus luteum secretes estrogen and progesterone -the corpus luteum degenerates throughout the phase due to low levels of LH

-estrogen and progesterone levels drop at the end of this phase signaling menstruation all over again

Pregnancy

-If fertilization / implantation occurs, the placenta produces human chorionic gonadotropin (hCG).

-hCG keeps the corpus luteum from degenerating in place of LH

-the corpus luteum maintains high levels of estrogen and progesterone (first 2-3 months)

-the placenta then takes over production of estrogen and progesterone for the remainder of pregnancy

-the endometrium isnt shed and ovulation doesnt occur during pregnancy (LH remains low)

67

Menstrual Cycle

Menses (Days 1-7) endometrium is sloughed off; signalled by low levels of estrogen and progesterone

Proliferative Phase (Days 7-14) increasing levels of estrogen lead to endometrial growth

Secretory Phase (Days 15-28) preparation for implantation -endometrial cells deposit lipids and glycogen in their cytoplasm

GnRH stimulates release of LH and FSH

-LH and FSH inhibit GnRH (negative feedback)

LH stimulates the follicle to produce estrogen

FSH stimulates the follicle to mature

-initiates and maintains spermatogenesis

Estrogen inhibits release of GnRH, LH, and FSH

Follicle also releases inhibin

-inhibits release of FSH

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Fertilization

-fertilization usually takes place in the fallopian tubes

-acrosome contains enzymes that allow the sperm to penetrate the corona radiata and zona pellucida

-usually a single sperm fertilizes an ovum

-depolarization and an influx in Ca2+

prevent subsequent sperm from penetrating

-sperm injects only its nucleus

-cytoplasm / organelles come from the mother

-after fertilization, the ovum completes meiosis II and the two nuclei fuse together (now called a zygote)

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Implantation

Embryogenesis

Fertilization

-fertilization usually occurs in the distal end of the fallopian tubes

-the journey to the uterus usually takes 4-5 days

Cleavage cell division with little cell growth -includes 2-celled, 4-celled, and 8-celled ultimately forming the morula

Blastocyst (Blastula) a hollow ball of ~100 cells -outer layer of cells is the trophoblast

-trophoblast becomes the chorion / placenta and secretes hCG

-inner cell mass adheres to one side

-inner cell mass will be the growing embryo

-blastocyst embeds in the endometrium (implantation)

-chorionic villi pierce the vascular endometrium

Gastrulation

-blastocyst folds in on itself forming three germ layers

Neurulation

-folding of the ectoderm to form the central nervous system

ECTODERM MESODERM ENDODERM

epidermis dermis respiratory epithelium

nervous system muscle and bone digestive epithelium

eyes and ears connective tissue digestive system

cardiovascular system bladder

lymphatic system

urinary system

reproductive system

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Birth

-typically occurs between weeks 38 and 40

-exact trigger(s) for the induction of labor are not known

1) Cervix softens and dilates / pelvic ligaments loosen (days leading up to labor)

2) Baby drops and pushes on the cervix 3) Cervical stretch triggers the release of oxytocin by the posterior pituitary gland

4) Oxytocin induces contractions

5) Contractions stretching contractions stretching (positive feedback cycle) 6) Baby exits birth canal

Lactation

-prolactin stimulates milk production

-estrogen and progesterone stimulate development of breasts / mammary glands but inhibit prolactin

-estrogen and progesterone levels fall after delivery

-prolactin levels increase ~10-fold

-suckling stimulates the release of prolactin and oxytocin (needed for mild release)

Developmental Mechanisms

Cell specialization is due to differential gene expression

Determination the choosing of a particular fate for cell type even though it isnt yet apparent Differentiation - the result of determination in which a cell has become a distinct cell type

Mechanisms of Differential Gene Expression

-Due to a difference in transcription (each cell has the same DNA)

1) Asymmetric segregation of cellular determinants

-determinants are typically mRNA for transcription factors or transcription factors themselves

2) Cell-to-cell communication (Induction)

a) extracellular signals (receptor-mediated)

b) direct contact

c) gap junctions

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Biology Day 10 Genetics and Evolution Genetics

Mendelian Concepts

Genotype the genetic makeup responsible for a particular trait

Phenotype an organisms observable traits (determined by genotype and environment)

Gene genetic material coding for a single gene product (peptide, rRNA or tRNA)

Locus the chromosomal location of a gene

Allele one variant of a gene

Homologous chromosomes chromosomes that code for the same set of genes - may have different alleles though (one from each parent)

Homozygous having two identical alleles for a gene

Heterozygous having two different alleles for a gene

Wild Type the normal or most prevalent allele in a population

Dominant an allele where only one copy is necessary to yield the corresponding phenotype

Recessive an allele where two copies are necessary to yield the corresponding phenotype

Complete Dominance when a heterozygote has the phenotype of only 1 of the alleles (the dominant one)

Codominance both inherited alleles are completely expressed (ex. blood types ABO)

Incomplete Dominance phenotypes of the progeny that are intermediate of the parental phenotypes (snap dragons homozygous red crossed with homozygous white gives pink progeny)

Leakage when a loss of function mutation doesnt result in complete lack of a phenotype

Penetrance the percentage of organisms having a certain genotype expressing a certain phenotype

Expressivity a term describing the variation in phenotype among organisms with a given genotype

Pleiotropism when a single gene affects multiple traits

Polygenism when multiple genes affect a single trait

Epistasis when the expression of a gene is dependent upon another gene

Gene Pool the set of all alleles in a population

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Meiosis

Nondisjunction failure of tetrads to separate during meiosis I or sister chromatids in meiosis II Examples: Down Syndrome (trisomy 21), Turner Syndrome (X), Kleinfelter Syndrome (XXY)

Translocation movement of a segment of one chromosome to another non-homologous chromosome

(ex. Down syndrome chromosome 21 14)

Interphase

G1

S

Protein and nucleic acid synthesis to prepare for replication; production of organelles

DNA Replication

Prophase I Longest phase

Chromosomes condense and tetrad formation (homologous pairs)

Recombination

Disappearance of the nuclear envelope and polarization of the centrioles (MTOCs)

Metaphase I Chromosomes line up on metaphase plate

Spindle fibers attach at centromeres via kinetochores

Anaphase I Spindle fibers pull homologous chromosomes apart towards the centrioles

Cleavage furrow begins forming

Telophase I Nuclear membranes reform

Completion of cytokinesis

Prophase II Chromosomes condense

Disappearance of the nuclear envelope and polarization of the centrioles (MTOCs)

Metaphase II Chromosomes line up on metaphase plate

Spindle fibers attach at centromeres via kinetochores

Anaphase II Spindle fibers pull sister chromatids apart towards the centrioles

Cleavage furrow begins forming

Telophase II Nuclear membranes reform

Completion of cytokinesis

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Segregation of Genes

Law of segregation separation of alleles into haploid gametes

Law of independent assortment genes assort independently to the progeny

Recombination (single and double crossovers) exchange of segments from homologous chromosomes -leads to new combinations of alleles

-occurs during prophase I of meiosis

Linked genes genes on the same chromosome wont necessarily undergo independent assortment -the closer together on the chromosome the greater the linkage between genes

-the likelihood of recombination occurring between two genes increases with distance between genes

Sex-linked Characteristics

-Autosomes vs. sex chromosomes (X and Y)

XX = female (one copy is inactivatedconverted into a Barr body) XY = male (Y chromosome has very few genes)

Y-linked traits rare as there are very few genes on the Y-chromosome -Y-linked disorders are passed on to male offspring only (100%)

X-linked traits males only receive a single copy of the X-chromosome (from their mother)

Turner Syndrome (X) offspring (female) have only a single X chromosome resulting from nondisjunction Kleinfelter Syndrome (XXY) offspring (male) have an extra X chromosome resulting from nondisjunction

Cytoplasmic / Mitochondrial inheritance chloroplast / mitochondrial DNA is inherited through a single parent -mitochondrial DNA is inherited through your mother

-any genetic disorders coded by the mitochondrial DNA will be passed on to all offspring

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Mutations

Most mutations are deleterious (rather than advantageous) to the cell.

Translational / transcriptional errors

Point mutation a single base substitution Missense mutation point mutation leading to a codon coding for a different amino acid Nonsense mutation point mutation leading to a premature stop codon

Frameshift mutation insertion or deletion leading to a change in the reading frame of a gene

Mutations in replication low level of natural mutations that occur during replication (random error)

Inborn errors of metabolism metabolic disorders caused by mutation (usually of a key enzyme)

Mutagen an agent that causes mutation Carcinogen an agent that can cause cancer (most are mutagens)

Population Genetics

Hardy-Weinberg Equilibrium allele frequencies remain constant in a gene pool for a population in equilbrium

p + q = 1 p = frequency of dominant allele

q = frequency of recessive allele

p2 + 2pq + q

2 = 1

p2 = frequency of homozygous dominant genotype

2pq = frequency of heterozygous genotype

q2 = frequency of homozygous recessive genotype

Crosses

Testcross crossing a dominant phenotype individual with a recessive to determine the dominant genotype

Backross crossing a hybrid (such as the F1) with one of the parents

Assumptions for equilibrium

1. Random mating

2. No mutations

3. No selection (natural or otherwise)

4 No migration

5. Large population size

(No genetic drift)

AA x aa

a a

A Aa Aa

A Aa Aa

Aa x aa

a a

A Aa Aa

a aa aa

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1) Homozygous yellow peas (dominant) are crossed with homozygous green peas (recessive). The F1

generation is then self-crossed. What will be the phenotypic ratios in the F2 generation?

2) For peas, yellow is dominant to green and round is dominant to wrinkled. Two heterozygous yellow, round

pea plants are crossed (YyRr). What are the phenotypic ratios in the F1 generation?

3) Color blindness is the result of an X-linked recessive allele. What is the probability that a color blind father

and a normal mother (homozygous) have a color blind child?

4) What is the probability that a heterozygous mother (a carrier) and a normal father have a color blind child?

What is the probability their daughter is color blind?

What is the probability their son is color blind?

6) Lets say that the color and size gene for an organism lie on the same chromosome:

B = blue, b = green, L = large, l = small

Two organisms that are heterozygous for both color and size with the dominant alleles paired on one

chromosome and the recessive alleles paired on the other are crossed and the offspring are as follows:

Phenotype Number

Blue and Large 70

Blue and Small 3

Green and Large 4

Green and Small 23

Which are the recombinant phenotypes?

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Evolution

Fitness the ability of an organism to pass on its alleles

Natural Selection differential reproduction of an organism based upon fitness in its environment -the alleles that confer fitness will increase in frequency in the gene pool over time

Types of Selection

1) Stabilizing Selection Selection against the extremes (for the averages) 2) Disruptive (Divergent) Selection Selection against the averages (for the extremes) 3) Directional Selection Selection against one extreme (but favoring the opposite extreme) 4) Artificial Selection directional selection done by humans with selecting for traits in animals and crops 5) Sexual Selection Differential mating between males and females

Speciation

Species group of organisms that are capable of interbreeding to produce fit offspring

Reproductive Isolation barriers preventing members of different species from producing fit offspring

Polymorphism the existence of multiple phenotypes within a population

Adaptation an inherited trait that confers greater fitness

Specialization an adaptation to a specific function or environment

Ecological Niche the sum of the environmental requirements required for a species to persist -includes habitat, predators, prey, etc.; thought of as being unique for each species

Inbreeding increased likelihood of mating between organisms with similar genotypes (limits genetic variation)

Outbreeding - increased likelihood of mating between organisms with different genotypes

Genetic Drift random change in allele frequencies in a population -smaller populations are more susceptible to genetic drift

Bottleneck dramatic decrease in size of a population making it susceptible to genetic drift

Convergent Evolution two species possess the same analogous structures unrelated to a common ancestor

Divergent Evolution divergence leading to distinct populations / species

Parallel Evolution similar evolutionary changes in different species due to similar environmental pressures

Symbiotic Relationships

1) Parasitism when a species requires another species as a host to live, harming the host in the process 2) Commensalism an organism requires another species as a host to live with no harm or benefit to the host 3) Mutualism symbiotic relationship between two organisms that confers fitness to both

Ontogeny and Phylogeny Similarities in stages of development (ontogeny) can be used to determine evolutionary relationships between organisms.

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Origin of Life

Panspermia life was seeded extraterrestrially (meteors, cosmic dust, etc.)

Life may have arisen on Earth and the most likely location would be the early oceans.

-possibly at the oceans edges or at deep-sea vents or ??? -possibly in a reducing atmosphere (no O2)

-organic molecules can be produced from a simple mixture of gases and electricity (Miller-Urey experiment)

-formaldehyde, HCN, urea, and even some amino acids resulted

-lipid bilayers spontaneously form in aqueous solution via self-assembly

-possibility of RNA acting as the original genetic material with the ability to self-replicate (ribozyme)

Somewhere along the way a collection of molecules began to live and self-replicate

Eventually these became the first cells and had all the attributes we associate with life:

1) Heredity and reproduction

2) Being distinct from its environment (cellular)

3) Capable of growth and development

4) The ability to respond to stimuli from the environment

5) Capable of homeostasis and regulation