I. Biochemistry and Cellular Respirationa) Thermodynamics

- First law of thermodynamics: the energy of the universe is constant energy of system decreases = the energy of the rest of universe must increase

- Second law of thermodynamics: the entropy (disorder) of the universe always increases- ΔG increases with increasing ΔH (bone energy) and decreases with increasing entropy (ΔG = ΔH

– TΔS)- ΔG < 0 spontaneous = no require energy input but it says nothing about the rate of reaction- Relate to the equilibrium constant: ΔG0’= -RT LnK’eq (equilibrium is defined as the point where

the rate of reaction in one direction equals the rate of reaction in the other. - Two factors that determine whether a reaction will occur spontaneously in the cell

a. The intrinsic properties of the reactants and products ΔG0’

b. The concentrations of reactants and productsc. In the lab: temperature

b) Kinetics and activation energy- A catalyst lowers the Ea of a reaction without change the ΔG. The catalyst lowers the Ea by

stabilizing the transition state, making its existence less thermodynamically unfavorable.- In test tube: the enzyme is a catalyst with a kinetic role influences the rate of the reaction, but

not the outcome- In real cell: enzyme controls outcomes by selectively promoting unfavorable reactions via

reaction coupling- The active site of enzymes is generally highly specific in its substrate recognition, including

stereo specificity.c) Regulation of enzyme activity

- Covalent modification (kinase vs phosphatase), proteolytic cleavage, association with other polypeptides, allosteric regulation

- Allosteric regulation: When bound, the allosteric regulator can alter the conformation of the enzyme to increase or decrease catalysis, even though it may be bound to the enzyme at a site distant from the active site or even on a separate polypeptide. Cooperatitivity is a special kind of allosteric interaction. One active site acts like an allosteric regulatory site for the other active sites. Secondly, cooperative enzyme complexes are often allosterically regulated also.

- Feedback inhibition (negative feedback)d) Basic enzyme kinetics

- If there is only a little substrate, then the rate V is directly proportional to the amount of substrate added: double the amount of substrate and the reaction rate doubles.

- At point the enzyme is said to be saturate Vmax- Km is the substrate concentration at which the reaction velocity is half its maximum.

e) Inhibition of enzyme activity- Competitive inhibition: molecules that compete with substrate for binding at active site

Vmax: no change, Km: increasing- Noncompetitive inhibition: bind at an allosteric site, not at the active site diminish Vmax, doe

not alter Kmf) Cellular respiration

- Three meanings of oxidize: attach oxygen, remove hydrogen, remove electrons- Three meanings of reduce: remove oxygen, add hydrogen, add electronsi. Glycolysis:- Hexokinase: catalyzes the first step in glycolysis, the phosphorylation of glucose to G6P.- Phosphofructokinase: catalyzes the third step: the transfer of a phosphate group from ATP to

fructose-6-phosphate to form fructose-1,6-bisphosphate committed step- 2 ATP and 2 NADH per glucose molecule in glycolysisii. Fermentation:- Regenerate NAD+ in anaerobic conditions- Reduction of pyruvate to ethanol- Reduction of pyruvate to lactate in human muscle cells. Lactate is exported from the muscle cell

to the liver. When oxygen becomes available, the liver cell will convert the lactate back to pyruvate, while making NADH from NAD+

iii. Pyruvate dehydrigenase complex:- Oxidative decarboxylation: a reaction repeated again in the Krebs cycle, in which a molecule is

oxidized to release CO2 and produce NADH.- The PDC changes pyruvate into an activated acetyl unit which is attached to a carrier, coenzyme

A.- Prosthetic group: a non protein molecule covalently bound to an enzyme as part of the enzyme’s

active site contains a thiamine pyrophosphate thiamine in thiamine pyrophosphate is vitamin B1. If the TPP is defect, the rate of glycolysis would increase.

- PDC form: 2NADHiv. The Krebs cycle:- Krebs cycle: 6 NADH, 2 FADH2, and 2 GTP per glucose- The two carbons that leave as CO2 during these reactions are not the same ones that entered the

cycle as acetate.v. Mitochondria:- Two goals of electron transport/oxidative phosphorylation:

Reoxidize all the electron carriers reduced in glycolysis, PDC, and Krebs cycleStore energy in the form of ATP in the process

- For prokaryotes: all of the reduced electron carriers are located in the cytoplasm. Bacteria use their cell membrane.

- Oxidative phosphorylation: oxidation of high-energy electron carriers NADH and FADH2 = coupled to the phosphorylation of ADP to produce ATP.

- Electron transport from NADH dehydrogenase coenzyme Q coenzyme Q reductase cytochrome C reductase cytochrome C cytochrom C oxidase O2

- The inner mitochondrial membrane is highly impermeable to protons the electron transport chain creates a large proton gradient, with the pH being much higher inside the matrix than in the rest of the cell.

- 1.5 ATP/FADH2 and 2.5 ATP/NADH.- Total: 30 ATP for eukaryote and 32 ATP prokaryotevi. Other metabolic pathways of the cell:- Glycogenolysis: glycogen breakdown- Glyconeogenesis: stores of glucose- Beta oxidation: Fatty acids are made in the cytoplasm of liver cells by fatty acid biosynthetic

pathways and are stored in fat cells as triglycerides. II. Molecular Biology

a) DNA structure- Nucleoside: include sugar + aromatic base- Nucleotide: include sugar + aromatic base + triphosphate- Phosphodiester bonds: between the 3’ hydroxyl group of one deoxyribose and the 5’ phosphate

group of the next deoxyribose- For Watson-Crick Model of DNA: right handed + antiparallel orientation + purine (A,G/ two

rings) plus a pyrimidine (T,C/ one ring)- Annealing: the binding of two complementary strands of DNA- Denaturation: separation of strands- For prokaryote DNA gyrase: use the energy of ATP to twist the gigantic circular molecule into

supercoils- For eukaryote: DNA is wrapped around globular protein called histones nucleosome:

composed of DNA wrapped around an octamer of histones + the string between the beads is a length of double-helical DNA = linker DNA.

- Deoxyribose add base nucleoside add three phosphate nucleotide polymerize with loss of two phosphates oligonucleotide continue polymerization single stranded polynucleotide two complete chains H-bonds in antiparallel orientation ds DNA chain coiling occurs ds helix wrap around histones nucleosomes complete packaging chromatin.

b) Replication:- After replication, pne strand of the new double helix is parental, and one strand is newly

synthesized daughter DNA DNA replication semiconservative

- Polymerization occurs in the 5’ to 3’ direction (newly DNA) - DNA pol requires a template- DNA pol requires a primer A special RNA polymerase called primase begins DNA replication

by creating a small RNA primer that DNA pol can elongate by adding deoxyribonucleotides to the existing ribonucleotide primer.

- Helicase: the enzyme that unwind the double helix and separate the strands, starting at origin of replication

- Topoisomerase: cut one or both of the strands and unwrap the helix- Single-strand binding protein: protect DNA which has been unpackaged in preparation for

replication and help keep the strands separated open complex.- DNA ligase: all RNA primers are replaced by DNA and fragment are joined

Eukaryotic Prokaryoticmany replication bubbles theta replication on one chromosome

DNA pol I DNA pol II DNA pol IIISlow, 5’ 3’ polymerize, 5’ 3’ exonuclease to remove RNA

primers

Unknown Fast, 5’ 3’ polymerize, 3’ 5’ exonuclease

c) Transcription- Type of RNA

o Single strandedo Contains Uracilo Ribose rather than 2’ deoxyriboseo Eukaryote (monocistronic/one gene one protein) vs Prokaryote (polycistronic/code for

more than one polypeptide)- Promoter: the sequence of nucleotides on a chromosome that activates RNA polymerase to begin

the process of transcription- Prokaryotic transcription:

o Core enzyme responsible for rapid elongation of the transcripto Sigma factor + core enzyme = holoenzyme initiate transcriptiono Initiation: RNA polymerase holoenzyme binds to a promoter (the Pribnow box at -10 and

-35 sequence) holoenzyme scans along the chromosome until it recognizes a promoter form a closed complex RNA polymerase bound at the promoter with a region of single-stranded DNAs form open complex

o Regulation (lac operon): DNA encoding a piece of mRNA that codes for three enzymes necessary for lactose catabolism + two regulatory sequences: the promoter and the lac operator with lactose (it binds to the repressor protein => repressor is no longer capable of binding to the operator) + without lactose (repressor binds to operator => stop the transcription of mRNA)

- Eukaryote transcription:o RNA pol I: transcribe rRNAo RNA pol II: transcribe mRNAo RNA pol III: transcribe tRNAo Slicing intronso 5’cap and the 3’ poly-A tail to prevent digestion of mRNA by exonucleaseso Regulation: Promoter at TATA box + Sequence-specific transcription factors + Enhancero Transcription and Spicing occur simultaneously in the nucleus

d) Translation:- tRNA:

o Composed of a single transcript produced by RNA polymerase IIIo Specific base pairing between the tRNA anticodon and the mRNA codono The other end of the tRNA molecule has the amino acid acceptor site, which is where the

amino acid is attached to the tRNAo Peptide bond formation during protein synthesis: require a lot of energy ΔG > 0

breaking the aminoacyl-tRNA bond will drive peptide bond formation

o Aminoacyl-tRNA synthetase enzyme specific to the amino acid recognize both the tRNA and the amino acid based upon three-dimensional structure

o Amino acid activation: attachment of amino acid to the tRNA specific amino acid delivery + thermodynamic activation of the amino acid

- Ribosome:o Eukaryote: 80S ribosome (60S and 40S in eukaryote)o Prokaryote: 70S ribosome (50S and 30S in prokaryote)o tRNA move through the sites A P E

- Prokaryotic translation:o Instead of promoter we have a ribosome binding site (Shine-Dalgarno sequence)o Initiation: formation of the 70S initiation complex + the first initiator tRNA = fMet-tRNAo Elongation: second aminoacyl-tRNA enters the A site and hydrogen bonds with the

second codon requiresthe hydrolysis of one phosphate from GTP peptidyl transferase activity of the large ribosomal subunit catalyzes the formation of a peptide bond between fMet and the second amino acid translocation: tRNA#1 moves into E site and tRNA#2 moves to P site (cost 1 GTP)

o Termination: a stop codon appears in the A site, a release factor now enters the A site- Eukaryotic translation:

o Start translation at Kozak sequence, which is a consensus sequence typically located a few nucleotide before the start codon

III. Microbiologya) Virus: an obligate intracellular parasite which relies on host machinery whenever possible.

- Bacteriophage: a virus that infects bacteria - Structure:

Viral genome: either DNA or RNA that is either single or double stranded and is either linear or circular. Size is limiting factor.

Capsid: a protein coat that is surrounding the viral nucleic acid genome. The genome is located within the capsid head.

Tail fibers: attach to the surface of the host cell Sheath: using the energy of stored ATP Animal virus – envelope: a membrane o the exterior of the virus derived from the membrane

of the host cell (from the host membrane in addition to proteins encoded by the viral genome)1. Bacteriophage life cycles: attachment/adsorption (binding to the exterior of a bacterial cell)

penetration/eclipse (capsid remains on the outer surface of the bacterium)a. Lytic cycle (as soon as the phage genome has entered the host cell host polymerase

begin to rapidly transcribe and translate it)o Hydrolase (early gene): a hydrolytic enzyme degrade the entire host genomeo Multiple copies of the phage genome are producedo Each new capsid automatically assembles itself around a new genomeo Lysozyme (late gene): human tears and saliva destroy the bacterial cell wall the

host bacterium bursts due to counteracting osmotic pressureb. Lysogenic cycle (phage genome is incorporated into the bacterial genome and is not

referred to as a prophage and the host is a lysogen)o The prophage is silient due to: transcription of phage genes is blocked by a phage-

encoded repressor protein that binds to specific DNA elements in phage promoters.o Excision: prophage becomes activated remove itself from the host genomeo Transduction: the present of the new DNA in the newly-infected hostc. Replication of animal virus:o Distribution of receptors on plasma membranes adsorptiono Endocytosis: many animal viruses enter cells (a process whereby the host cell engulfs the

virus and internalizes it) o Either lytic cycle (but does not destroy the host cell exit the host cell by budding

through the host’s cell membrane) + lysogenic cycle (provirus)Bacteriophage life cycles: attachment/adsorption (binding to the exterior of a bacterial cell)

2. Viral Genomes: a. (+) RNA virus: must encode RNA-dependent RNA polo A piece of single-stranded viral RNA which serves as mRNA acts as mRNA inside

host cello In order for the virus to replicate itself, one of the proteins it encodes must be an RNA-

dependent RNA polymerase to copy the RNA gemone for viral replicationb. (-) RNA virus: must carry RNA-dependent RNA polo The genome of a (-) RNA virus is complementary to the piece of RNA that encodes viral

proteins.c. Retrovirus: must encode reverse transcriptaseo Since these viral genomes enter the cell in an RNA form, they must undergo reverse

transcription to make DNA from an RNA template.d. Double-stranded DNA virus: often encode enzymes required for dNTP synthesis and

DNA replicationb) Prokaryotes: do not contain membrane-bound organelles and lack of nucleus

- Structure:o Cytoplasm:

i. The prokaryotic genome: a single double-stranded circular DNA chromosomeii. Transcription and translation occur in the same place at the same timeiii. Plasmid: extrachromosomal genetic elements

o Cell membrane and cell walli. Cell membrane: a lipid bilayer which is similar to animal plasma membraneii. Cell wall: rigid, a lipid bilayer outside cell membrane – composed of peptidoglycan –

bacteria without cell wall = protoplastiii. Gram staining of the cell wall

- Gram positive : thick peptidoglycan layer which contacts to extracellular environment

- Gram negative : outer membrane with endotoxin which contacts to extracellular environment + periplasmic space (thin peptidoglycan)

- Endotoxin vs exotoxin – Endotoxin: normal components of the outer membrane of Gram-negative bacteria – Exotoxin: toxic substances secreted by both Gram-negative and Gram-positive

o Capsule: sticky layer of polysaccharide surrounding the bacterial cell and often surrounding an entire colony of bacteria.

o Flagella: long, whip-like filaments bacterial motility prokaryotic flagellum: contains a “9+2” arrangement of microtubules the connection between chemotaxis and flagellar propulsion is dependent upon chemoreceptors on the cell surface that bind attractants or repellents and transmit a signal which influences the direction of flagellar rotation

o Pili: long projections on the bacterial surface involved in attaching to different surfaces- Shape: spherical bacteria = cocci, rod-shaped bacteria = bacilli, helical bacteria = spirochetes or

spirilla- Growth Requirements:

o Temperatureo Nutrition: chemoautotroph – build organic macromolecules from CO2 using the energy

of chemicals, chemoheterotroph – require organic molecules as their carbon source and for energy, photoautotroph – use CO2 as a carbon source and obtain their energy from the Sun, photoheterotroph – get energy from Sun and require an organic molecule as their carbon source

o Growth media: require auxiliary trophic substance to live (cannot survive on minimal medium because it can’t synthesize a molecule it)

- Oxygen utilization and tolerance:o Bacteria which require oxygen: obligate aerobeso Bacteria which does not require oxygen: facultative anaerobes (use oxygen when it’s

around, but don’t need it), tolerant anaerobes (grow in the presence or absence of oxygen, but don’t use in their metabolism), obligate anaerobes (poison by oxygen)

o Anaerobic respiration: relying on an external electron acceptor other than O2- Bacterial Life Cycle:

o No meiosis = binary fission = asexual reproductiono Sexual reproduction = conjugation for exchanging genetic informationo Lag phase/Prior to achieving exponential growth Log phase/Grows linearly with time

Stationary phase/Cells cease to divide for lack of nutrients o Carrying capacity: maximum population at the stationary phaseo Germination: the metabolic reactivation of an endospore/tough, thick external shells

comprised of peptidoglycan cannot increase their population through spore formation- Genetic exchange between bacteria

o Conjugation: bacteria make physical contact and form a bridge between cells After the male cell produce sex pili and the pili contact a female cell = a conjugation bridge The F factor is replicated and transferred from the F+ to F- cell (Fertility factor = an extrachromosomal element)/ A cell with the F factor integrated into its genome (Hfr = high frequency of recombination)

o Conjugation between Hfr and F- the conjugation of an Hfr cell with an F- cell does not usually result in an F+ cell the F factor usually remains in the Hfr cell

c) Fungi- Structure: yeast/unicellular, fungi/multicellular eukaryote chemoheterotroph

o Chitin: a rigid cell wallo Saprophyte: feed off dead plants and animalso Parasites: feed off living organismso Mutualism: live in a symbiotic relationshipo Hypha: a long filament of cells joined end-to-end septate hyphae (separated by walls)/

aseptate hyphae (composed of cells joined together in a long tube)o Haustoria: hypae that are specialized to digest and absorb nutrients in a parasitic fashiono Mycelium: a meshwork of hyphaeo The vegetative portion of the thallus is involved in obtaining nutrientso The fruiting body: functions in reproduction

- Life cycleo Asexual reproduction: budding (a new smaller hypha grows outward from an existing

one), fragmentation (mycelium can be broken into small pieces), asexual spore formation (mitosis to generate many spores from one cell) multiple identical genetic clones of the original fungi

o Sexual reproduction: Fungal adults are haploid rather than diploid fusion of haploid fungal gametes produces a diploid zygote the diploid zygote quickly enters meiosis to produce haploid cells divide by mitosis to produce a new haploid adult.

IV. Eukaryotic Cellsa) Nucleus

- Genome + nuclear envelope- Prokaryote: replication + translation and transcription occur in cytoplasm

- Eukaryote: replication, transcription and splicing occur in the nucleus + translation occur in the cytoplasm

- Genome: chromosome is a separate linear DNA molecule centromere: near the middle to ensure that newly replicated chromosomes are sorted properly during cell division telomere: large numbers of repeats of a specific DNA sequence with the help of telomerase genes reside on a specific location on chromosome: locus (region that genes tend to be inaccessible and turned off = heterochromatin, region that genes tend to be activated = euchromatin) nuclear matrix: support and provide over structure

b) Nucleolus: a region within the nucleus which functions as a ribosome factory + the site of transcription of rRNA by RNA pol Ic) Nuclear envelope: punctuated with large nuclear pores that allow the passages of material into and out of the nucleus large proteins contain nuclear localization sequence can pass through nuclear pores the nuclear localization mechanism is nonspecificd) Mitochondria: site of oxidative phosphorylation

- Emdosymbiotic theory: Many unique mitochondrial polypeptides are encoded by the cellular genome and not the mitochondrial genome

- Maternal inheritance: mitochondria are inherited only from the mother, since the cytoplasm of the egg becomes the cytoplasm of the zygote

e) Endoplasmic reticulum: a large system of folded membrane including rough ER and smooth ER- Proteins are synthesized on the rough ER will end up: secreted into the extracellular environment

+ integral plasma membrane proteins + in the membrane or interior of the ER, Golgi apparatus, or lysosomes

- Some proteins have an amino acid sequence at their N-terminus: signal sequence is recognized by the signal recognition particle, which binds to the ribosome.

- Integral membrane proteins: have sections of hydrophobic amino acid residues = transmembrane domains that pass through lipid bilayer membranes not removed after translation (plasma membrane)

- Targeting signal: go to different organelle (lysosome, rough/smooth ER, Golgi apparatus)- Localization signal: sent to an organelle not part of secretory path (nucleus, mitochondria,

peroxisome)f) Golgi apparatus: The portion of the Golgi nearest the rough ER = cis stack (protein receiving), the part farthest from rough ER = trans stack (protein leaving)

- Constitutive secretory path: vesicles from the Golgi to the cell surface- Regulated secretory pathway: store secretory proteins in secretory vesicles and release them only

at certain timesg) Lysosome:

- Responsible for the degradation of biological macromolecules by hydrolysis- Acid hydrolases: enzyme responsible for degradation in lysosomes

h) Peroxisome:- Catalase: covert peroxide into water and oxygen

i) Plasma membrane:- Protein

o Integral membrane protein: embedded in the membrane, held there by hydrophobic interactions

o Peripheral membrane protein: not embedded in the membrane at all, but rather are stuck to integral membrane proteins, held there by hydrogen bonding and electrostatic interactions

- Fluidity:o Saturated fatty acids (lacking any double bonds): strong van der Waals forces between

side chainso Unsaturated fatty acids (with one or more double bonds): weak van der Waals forces o Cholesterol: plays a key role in maintaining optimal membrane fluidity by fitting into the

membrane interior- Transport:

o Diffusion: solute moves toward equilibriumo Osmosis: solvent moves toward equilibrium

o Passive: any thermodynamically favorable movement of solute across a membrane down a gradient

Simple diffusion: diffusion of a solute through a membrane without help from a protein

Facilitated diffusion: movement of solute across a membrane, down a gradient with the help of channel protein and carrier protein

Kinetics: Simple diffusion is limited only by the surface area of the membrane and the size of the drive force v.s. facilitated diffusion depended on the saturation of transport proteins.

o Active: require energy input to be thermodynamically favorable (ΔG < 0) Primary active transport: directly couple to ATP hydrolysis Secondary active transport: not coupled directly to ATP hydrolysis

o Na+/K+ ATPase and the resting membrane potential Pump 3 Na+ out of the cell, 2 K+ into the cell by hydrolyzing one ATP to drive

the pumping of these ions against their gradients Sodium leak channels: some of the potassium ions which are pumped into the

cell are able to leak back out Resting membrane potential: potassium leaves the cell through the leak channels,

the movement of positive charge out of the cell creates an electric potential across the plasma membrane with a net negative charge on the interior of the cell

To maintain osmotic balance between the cellular interior and exterior To establish the resting membrane potential To provide the sodium concentration gradient used to drive secondary active

transporto Exocytosis: a process to transport material outside of the cell in which a vesicle in the

cytoplasm fuses with the plasma membrane and the contents of the vesicle are expelled into the extracellular space

o Endocytosis: Phagocytosis: cell eating = nonspecific uptake of large particulate matter into

phagocytic vesicle, which later merges with a lysosome Pinocytosis : cell drinking = non specific uptake a small molecules and

extracellular fluid via invagination Receptor-mediated endocytosis: the site of endocytosis is marked by puts coated

with the molecule clathrin and with receptors that bind to a specific moleculej) Cell-surface receptors:

- Epinephrine arrives at the cell surface and binds to a specific G-protein-linked receptor- The cytoplasmic portion of the receptor activated G-proteins, causing GDP to dissociate and GTP

to bind in its place- The activated G-protein diffuse through the membrane and activate adenylyl cyclase- Adenylnyl cyclase makes cAMP from ATP- cAMP activates cAMP-dependent protein kinases in the cytoplasm- cAMP-dependent protein kinases phosphorylates certain enzymes, with the end result being

mobilization of energyk) Cytoskeleton:

- Microtubules: a hollow rod composed of two globular proteins: alpha-tubulin and beta-tubulin. o One end cannot elongate, one is anchored to the microtubule organizing center, located

near the nucleuso Within the MTOC is a pair of centrioleso Aster: the microtubules that radiate out form the centrioles during mitosiso Polar fibers: the microtubules connecting the chromosomes to the astero Kinetochore: which is attached to the spindle

- Eukaryotic cilia and flagella: o Each microtubule is bound to its neighbor by a contractile protein called dynein which

causes movement of the filaments past one anothero The cilium or flagellum is anchored to the plasma membrane by a basal body, which has

the same structure as a centriole

- Microfilament: rods formed in the cytoplasm from polymerization of the globular protein actino Microfilaments are dynamic and are responsible for gross movements of entire cell and

amoeboid movement: changes in the cytoplasmic structure which cause cytoplasm and the rest of the cell to flow in one direction.

- Intermediate filaments: resisting mechanical stressl) Cell adhesion and cell junctions

- Tight junction: layer of epithelia cells in the gut forms a tight seal- Desmosome: epithelia cells in the skin are held together tightly but do not form a complete seal

anchored to the plasma membrane by a plaque formed by the protein keratin- Gap junction: allow ions to flow back and forth between them

m) Cell cycle and mitosis:- S phase: cell actively replicates its genome- M phase: mitosis (partitioning of cellular components into two halves) and cytokinesis (physical

process of cell division)- Gap phases plus S phase interphase- Mitosis: prophase metaphase anaphase telophase- Sister chromatids are identical copies of a chromosome, attached to each other at the centromere.

Homologous chromosomes are equivalent but nonidentical and do not come anywhere near each other during mitosis.

V. Genetics and Evolutiona) Incomplete dominance: the phenotype of a heterozygote is a blended mix of both allelesb) Codominance: two alleles are both expressed but are not blended.

- ABO blood group antigens: IA, IB, and i. The alleles IA and IB are codominant and will be expressed regardless of the second allele, while I is recessive to both IA and IB. The alleles IA and IB cause type A or type B antigens to be expressed, while i does not cause antigen expression.

- The other main antigen in blood: Rh factor. - Pleiotropism: alteration of a gene is said to have pleiotropic effects if the result alters many

different, seemingly unrelated aspects of the organism’s total phenotype.- Polygenism: complex traits that are influenced by many different genes are called polygenic.- Penetrance: a person with a given genotype will express the expected phenotype. - Epistasis: expression of alleles for one gene is dependent on a different gene c) Sex Chromosomes:- Sex-linked traits: traits that are determined by genes on the X or Y chromosome because of their unique patterns of expression and inheritance.d) Meiosis:- In male: meiosis occurs in spermatogonia- In female: meiosis occurs in oogonia- The primary difference between meiosis and mitosis is that replication of genome is followed by

one round of cell division in mitosis and two rounds of cell division in meiosis.- Prophase I: homologous chromosomes pair with each other during meiotic prophase I in synapsis

(bivalent or tetrad) crossing over occur between homologous chromosomes, not sister chromatids

- Metaphase I: sister chromatids are aligned on the metaphase plate- Anaphase I: homologous chromosomes separate and sister chromatids remain together cells

are considered to be haploid- Meiosis II begins immediately after telophase I anaphase II: separation of sister chromatidse) Nondisjuction: a failure of chromosome to separate correctly during meiosisf) Mendelian genetics:- Law of segregation: two alleles of an individual are separated and passed on to the next

generation singly- Law of independent assortment: the alleles of one gene will separate into gametes independently

of alleles for another geneg) Linkage: the exception to the law of independent assortment- The frequency of recombination between two genes on a chromosome is proportional to the

physical distance between the genes along the linear length of the DNA molecule. The frequency

of recombination is the number of recombinant phenotypes resulting from a cross divided by the total number of progeny

h) Inheritance patterns and pedigreesInheritance Pattern Identification TechniquesAutosomal recessive Can skip generation

Number of affected males is usually equal to the number of affected females

Autosomal dominant Does not skip generationsNumber of affected males is usually equal to number of affected femalesAn affecter parent passes the trait to either all or half of offspring

Mitochondrial Maternal inheritanceAffected female has all affected childrenAffected male cannot pass the trait onto his childrenUnaffected female cannot have affected children

Y-Linked Affected male only, females never have the traitAffected father has all affected sonsUnaffected father cannot have an affected son

X-linked recessive Can skip generationsTend to affect males more than femalesUnaffected females can have affected sonAffected female has all affected sons, but can have both affected or unaffected daughter

X-linked dominant Hardest to identifyDoes not skip generationsUsually affects males more than femalesAffected fathers have all affected daughterAffected mothers can have unaffected sons, and pass the trait equally to sons and daughters

i) Population genetics:- Hardy-Weinberg in population genetics: the frequencies of alleles in the gene pool of a

population will not change over time:i. There is no mutationii. There is no migrationiii. There is no natural selectioniv. There is random matingv. The population is sufficiently large to prevent random drift in allele

frequenciesvi. p2 + q2 + 2pq = 1 and (p + q)2 = 1 (q2: frequency of homozygous recessive,

p2: frequency of homozygous dominant, 2pq: frequency of heterozygous)- After one generation, a population will reach Hardy-Weinberg equilibrium, in which allele

frequencies no longer change. Since allele frequencies do not change, and genotype frequencies can be calculated from allele frequencies, it follows that genotype frequencies also do no change over time

j) Evolution by natural selection- Natural selection: an interaction between organisms and their environment that causes differential

reproduction of different phenotypes and thereby alters the gene pool of a population.i. In a population, there are heritable differences between individuals

ii. Heritable traits produce traits that affect the ability of an organism to survive and have offspring

iii. Some individuals have phenotypes that allow them to survive longer, be healthier, and have more offspring than others

iv. Individuals with phenotypes that allow them to have more offspring will pass on their alleles more frequently than those with phenotypes that have fewer offspring

v. Over time, those alleles that lead to more offspring are passed on more frequently and become more abundant, while other alleles become less abundant in the gene pool

vi. Changes in alleles frequency are the basis of evolution in species and populations

- Fitness: how successful it is in passing on its alleles to future generations- Source of genetic diversity: New alleles (mutation in genome) and new combinations of existing

alleles (recombination).- Modes of natural selection

i. Directional selection: If natural selection removes those at one extreme, the population average over time will move in the other direction

ii. Divergent selection: Natural selection removes the members near the average over time divergent selection will split the population in two and perhaps lead to a new species.

iii. Stabilizing selection: both extremes of a trait are selected against, driving the population closer to the average

iv. Artificial selection: human intervene in the matingv. Sexual selection: have evolved elaborate rituals and physical display that

play a key role in attracting and choosing a matevi. Kin selection: animals that live socially often share alleles with other

individualsk) Species concept and speciation

- Reproductive isolation keeps existing species separate- Prezygotic: barriers prevent the formation of a hybrid zygote- Postzygotic: barriers to hybridization prevent the development, survival or reproduction of hybrid

individuals- Speciation: the creation of new species

i. Cladogenesis: branching speciation one species diversifies and becomes two or more new species allopatric isolation (geographical isolation) divergent evolution

ii. Anagenesis: one biological species simply becomes another by changing so much

iii. Homologous structures: physical features shared by two different species as a result of a common ancestor.

iv. Analogous structures: same function in two different species, but not due to common ancestry convergent evolution

v. Parallel evolution: two species go through similar evolutionary changes due to similar selective pressures.

VI. The Nervous and Endocrine SystemsVII. The Circulatory, Lymphatic, and Immune Systems

a) Overview of the circulatory system- Distribute nutrients from digestive tract, liver, and fat tissue

- Transport oxygen from the lungs to the entire body and carbon dioxide from the tissues to the lungs

- Transport metabolic waste products from tissues to the excretory system- Transport hormones from endocrine glands to targets and provide feedback- Maintain homeostasis of body temperature- Blood clotting- Perfusion: the flow of blood through a tissue ischemia: inadequate blood flow due to shortages

of O2 and nutrients, and buildup of metabolic wastes hypoxia: adequate circulation is present but the supply of oxygen is reduced and wastes are adequately removed

- Heart: a muscular pump that forces blood through a branching series of vessels to the lungs and the rest of the body

- Arteries: vessels that carry blood away from the heart at high pressure- Vein: vessels that carry blood back toward the heart at low pressure- Arteries arterioles, smaller arteries capillaries, very small vessels- Pulmonary circulation: the flow of blood from the heart to the lungs and back to the heart right

side: blood to the lungs, left side: pumps blood to the rest of the body- Portal system: blood passes through several sets of capillaries before returning to the heart.

b) Heart- Vein, low pressure atria, high pressure ventricle artery, high pressure- Right side: the right atrium receives deoxygenated blood from the systemic circulation (from

inferior vena cava and superior vena cava) and pump it into the right ventricle go to pulmonary artery to the lungs (no oxygen blood)

- Left side: oxygenated blood from the lungs returns through the pulmonary veins to the left atrium and is pumped into the left ventricle before being pumped out of the heart in a single large artery (aorta) to the systemic circulation (oxygen blood) (Note: left ventricle would pump blood in both directions: out the aorta and back into the left atrium)

- Coronary veins which merge to form the coronary sinus (not end up in the inferior vena cava or superior vena cava) right atrium coronary arteries (aorta)

c) Valves: ensure one-way flow through the circulatory system (ventricular pressure, high pressure atrioventricular valve atrial pressure, low pressure)- Bicuspid: the AV valve between the left atrium and the left ventricle- Tricuspid: the AV valve between the right atrium and the right ventricle- Pulmonary and aortic semilunar valves semilunar valves

d) Cardiac cycle:- Two periods: diastole and systole- For diastole: Atria contract blood flow into relaxed ventricles- For systole: Ventricles contract atrioventricular valve close semilunar valves fly open

blood rushes into the aorta and pulmonary artery (Note: during systole, pressure in the atria is low, and thus the atria fill with blood from the vena cava and pulmonary veins.

e) Hear sounds, heart rate, and cardiac output- The heart rate/pulse is the number of times the closure of the atrioventricular valve at the

beginning of systole and the closure of the semilunar valve at the end of systole.- Stroke volume: the amount of blood pumped with each systole- Cardiac output: the total amount of blood pumped per minute = SV x HR

f) The Frank-Starling mechanism and venous return- Two principal ways to increase venous return (the return of blood to the heart by the vena cava):

increase the total volume of blood in the circulatory system/contraction of large veins can propel blood toward the heart.

g) Cardiac Muscle:- Functional syncytium: a tissue in which the cytoplasm of different cells can communicate via gap

junctions (found in intercalated disks which is the connections between cardiac muscle cells)- Cardiac conduction system: the action potential in the heart is transmitted from the atrial

syncytium to the ventricles- Voltage gated sodium channels (slow calcium channel): these channels open in response to a

change in membrane potential to a specific voltage allow the passage of calcium down its gradient these channels also stay open longer than the fast sodium channels do (causing the

membrane depolarization to last longer in cardiac muscle than in neurons, producing a plateau phase.

- The result of long depolarization in cardiac muscle increase the calcium concentration inside the cell because of allowing the entry of calcium ion from the extracellular environment and induce the sarcoplasmic reticulum to release calcium by T tubule contraction of actin-myosin fibers strengthening the force with which blood is expelled.

h) Rhythmic excitation of the heart:- The initiation of each action potential: occurs in the sinoatrial node of the right atrium. Under

normal circumstances, the cells of the SA node act as the pacemarker of the heart. - Inside the SA node unstable resting potential

i. Phase 4: slow depolarization by sodium leak channel that are responsible for its rhythmic, automatic excitation inward sodium leak brings the cell potential to the threshold for voltage-gated calcium channels

ii. Phase 0: the upstroke of the pacemaker potential an inward flow of Ca2+iii. Phase 3: repolarization closure of the Ca2+ channels and opening of the

Ki+ channels leading to an outward flow of K+ from the cell- Inside cardiac muscle cells:

i. Phase 0: depolarization, action potentials propagating through the intercalated discs stimulate myocytes to reach threshold for voltage-gated Na+ channels the Na+ channels open and Na+ rushes into the cell (Na+ influx)

ii. Phase 1: initial repolarization, the Na+ channels inactivate and K+ channels open an efflux of K+ and a slight drop in cell potential (Na+ channels inactivate, K+ channels open K+ efflux)

iii. Phase 2: plateau phase the influx of Ca3+ ions balance the K+ efflux from the phase one, leading to a transient equilibrium in cell potential (Ca2+ channels open Ca2+ influx, K+ channels still open K+ efflux)

iv. Phase 3: repolarization, Ca2+ channels close and the K+ channels continue to allow K+ to leave the cell (Ca2+ channels close, K+ channels still open K+ efflux)

v. Phase 4: which inward and outward current are equal (K+ channels close)i) Regulation of the heart by the autonomic nervous system:

- The autonomic nervous system does not initiate action potentials in the heart only regulate the rate of contraction

- The role of parasympathetic system in controlling the heart is the modulate the rate by inhibiting rapid automaticity

j) Hemodynamics: study of blood flow driven force: a difference in pressure from arteries to veins- Resistance: the force opposing flow ΔP = Q x R (Q: blood flow, R: resistance)- To change resistance the degree of constriction of arteriolar smooth muscle, precapillary

sphincters If arteriolar smooth muscles contract, it becomes more difficult for blood to flow from arteries into capillaries.

- The sympathetic nervous system controls the peripheral resistancek) Blood pressure:

- Systolic pressure/diastolic pressure ventricles contract- Pulse pressure is the difference between systolic and diastolic pressures.

l) Autoregulation: certain metabolic wastes have a direct effect on arteriolar smooth muscle causing it to relax.

m) Components of blood: plasma (electrolytes and buffers)+ formed elements- Blood proteins

i. Albumin is essential for maintenance of oncotic pressure, osmotic pressure in the capillaries due only to plasma proteins

ii. Immunoglobulins: key of immune systemiii. Fibrinogen: blood clottingiv. Lipoproteins: large particles consisting of fats, cholesterol, and carrier

proteins.v. Erythrocytes (Red blood cells)

a. Erythropoeitin: stimulates RBC production in the bone marrowb. Nu nucleus or other organelles such as mitochondriac. Rely on glycolysis for ATPd. Hemoglobin to carry oxygen

vi. Blood typing: a. Hemolytic disease of the newborn (mother Rh-, baby: Rh+):

some Rh+ cells from the child can mix with the mother’s Rh- blood and lead to her sensitization

vii. Leukocytes: fight infection and dispose of debris, move by amoeboid motility – cell crawling.Macrophage phagocytose debris and

microorganisms, amoeboid motility, chemotasis: movement directed by chemical stimuli

B cell mature into plasma cell and produce antibodies

T cell Kill virus-infected cells, tumor cells, and reject tissue grafts, also control immune response

Neutrophil Phagacytose bacteria resulting in pus, amoeboid motility, chemotaxis

Eosinophil destroy parasites, allergic reactionsBasophil Store and release histamine, allergic

reactions

viii. Platelets (from megakaryocytes inside bone marrow cells) and Hemostasis (mechanism of preventing bleeding):

a. Fibrin: a threadlike protein hold the platelet plug togetherb. Fibrinogen fibrin by thrombin

n) Transport of gasesa. Oxygen: Low O2 affinity due to decreasing pH, increasing PCO2, and

increasing temperatureb. Carbon Dioxide: Carbonic anhydrase: covert CO2 into bicarbonate ,

some carbon dioxide is transported by simply being stuck onto hemoglobin

c. Exchange of substances across the capillary wall:i. The capillaries are the site of exchange between the blood

and tissues three types of substance must be able to pass through the cleft: nutrients, wastes, and white blood cells.

ii. Hepatic portal vein: absorb A and glucose from the digestive tract

iii. Lacteals: the lipoprotein enter tiny lymphatic vessels in the intestinal wall lipoprotein carries fats to adipocytes for storage

iv. The hydrostatic pressure created by the heart simply tends to squeeze water out of the capillaries

v. The high osmolarity of the tissues tends to draw water out of the bloodstream (oncotic pressure) at the beginning of the capillary, the hydrostatic pressure is high, the result is that water squeezes out into the tissues As water continues to leave the capillary, the relative concentration of plasma proteins increases at the end of capillary the hydrostatic pressure is quite low, but since the blood is now very concentrated, the oncotic pressure is very hight. As a result, water flows back into the capillary from the tissues

o) The lymphatic system:

- Lymph nodes: contain millions of white blood cells that can initiate an immune response against anything foreign.

p) Immune system:- Innate immunity: non-specific protein the body provides against various invaders skin

i. The skin is an excellent barrier against the entry of microorganisms

ii. Tears, saliva, and blood contain lysozyme, an enzyme that kills some bacteria by destroying their cell walls.

iii. The extreme acidity of the stomach destroys many pathogens which are ingested with food or swallowed after being passed out of the respiratory tract.

iv. Macrophages and neutrophils indiscriminately phagocytize microorganisms

v. The complement system is a group of about 20 blood proteins that can non-specifically bind to the surface of foreign cells, leading to their destruction.

- Humoral Immunity, antibodies, and B cells:i. Binding of antibody may directly inactivate the antigenii. Binding of antibody can induce phagocytosis of a particle by

macrophages and neutrophils.iii. The presence of antibodies on the surface of a cell can

activate the complement system to from holes in the cell membrane and lyse the cell.

iv. B cells Plasma cells: actively produce and secrete antibody protein into the plasma. Memory cells: are produced from the same clone and have the same variable regions, but do not secrete antibody.

v. Clonal selection: method of selecting B cells with specific antigen binding Antigen stimulates profliferation of a specific B cell clone expressing a single antibody protein that recognizes that antigen.

- Cell-mediated immunity and the T cell:i. T helper: CD4 cells activate T killer: CD8 cells, B cellsii. The role of T killer cell: to destroy abnormal host cells:

virus-infected host cells, cancer cells, foreign cells such as the cells of a skin graft given by an incompatible donor

VIII. The Excretory and Digestive IX. The Muscular and Skeletal Systems

a) Skeletal musclei. Movement of joints

-X. The Respiratory System and The SkinXI. The Reproductive SystemsXII. Some Molecular Biology Techniques