Anat and Phys Unit 1
Introduction to Anatomy and Physiology
Anatomy is the study of structure
Physiology is the study of function
Structure determines the function and the function determines the structure
How to Study Anatomy
Examining structure of the human body
Inspection - viewing
Palpation - feeling
Auscultation - listening
Percussion - tapping
Cadaver dissection - cutting and separating human body tissues to reveal tissue relationships
Comparative anatomy - study of multiple species to learn about form, function, and evolution
Exploratory surgery
Physical light
Endoscopic
Medical imaging - viewing the inside of the body without surgery
Radiology - branch of medicine concerned with imaging
Uses electronic waves other than visible light
Medical Imaging
Radiography (x-rays)
Dense tissue appears white
Over half of all medical imaging
Most common and the oldest
Shows hard and soft tissues
Radiopaque substance
Liquids that show up on x-rays, showing the pathway the substance takes
Can be injected or swallowed
Fills hollow structures
Blood vessels
Intestinal track
In the human body hollow spaces are called lumens
Computed tomography (CT scan)
Formerly called a CAT scan
Low intensity x-rays and computer analysis
Show twists
Have more detail and can tell the differences between tissues
Magnetic resonance imaging (MRI)
Superior quality to CT scan
Best for soft tissue
Uses a strong magnet
All atoms on the surface point the same way (electrons spin the same way instead of opposite), electrons flip back and images are generated
Easiest electrons to see are closest to the nucleus
Focus on things in the body that contain lots of water
Positron emission tomography (PET scan)
Assesses metabolic state of tissue
Distinguishes tissues most active at any given moment
Mechanics - inject radioactively labeled glucose
Put radioactive barium into glucose, will be absorbed into the parts of the body that consume the most glucose (high metabolic)
Kidneys, liver, heart, and nervous system
Can see tumors
Can see which parts of the brain are working the hardest - highest metabolic load
Sonography
Second oldest and second most widely used
High frequency sound waves echo back from internal organs
Avoids harmful x-rays
Electromagnetic waves are not used, sound waves are
Can see the density and shape of what is being bounced off of
Does not mutate the genome so will not increase cancer risk
Fields of Anatomy
Gross anatomy - study of structures that can be seen with the naked eye
Histology - examination of tissues with microscope
Looks at cells in tissues to determine function
Cytology - study of structure and function of cells
Cyto - cell
The Hierarchy of Complexity
Organism composed of organ systems
Organ systems composed of organs
Organs composed of tissues
Tissues composed of cells
Cells composed of organelles
Organelles composed of molecules
Molecules composed of atoms
All work together for a common purpose
Anatomical Variation
No two humans are exactly alike
Anatomy books show most common organization of structres
Some individuals lack certain muscles
Some individuals have an atypical number of vertebrae
Some individuals have an atypical number of certain organs
Example: kidenys
Some individuals show situs inversus
Left-right reversal of organ placement
Inside there are many differences between everyone
Only 40% of people have the “normal” branches in the aorta
Characteristics of Life
Organization - living things exhibit a higher level of organization than nonliving things
Cellular composition - living matter is always compartmentalized into one or more cells
Metabolism - internal chemical reactions
Responsiveness - ability to sense and react to stimuli
Irritability or excitability
Movement - of organism and/or substances within the organism
Homeostasis - maintaining relatively stable internal conditions
Development - differentiation of growth
Reproduce - producing copies of themselves, passing genes to offspring
Evolution - changes genes from one generation to the next
Need to display all characteristics
Aging and Senescence
Aging - all changes occurring in the body with the passage of time
Growth, development, and degenerative changes that occur later in life
Senescence - the degeneration that occurs in organ systems after the age of peak functional efficiency
Gradual loss of reserve capacities, reduced ability to repair damage and compensate for stress, and increased susceptibility to disease
High senescence example: female reproductive system
Low senescence example: endocrine system
Peak is in late teens to early twenties
Male muscle mass - 30
Skin 50s-60s
Sun and physical habits influence senescence
1 in 8 Americans is 65 or older
Senescence is an important issue for American health care
Heart disease, cancer, stroke, and other illnesses are related to senescene
Cause of senescence is unclear
Personal health and fitness practices can lessen effects of senescence
The senescence of one organ system typically leads to senescence of other organ systems
Cascade of failures
Organ systems to do degenerate at the same rate
Some show moderate changes, while others show pronounced differences
When social security came out the average age of death was 67
Reasons for longer lifespan
Safety guidelines - fewer industrial accidents
Antibiotics
Exercise and Senescence
Good nutrition and exercise are best ways to slow senescence
Exercise improves quality of life by maintaining endurance, strength, and joint mobility
Reduces incidence and severity of hypertension, osteoporosis, obesity, and diabetes mellitus
90 year old can increase muscle strength threefold in 6 months with 40 minutes of isometric exercise per week
Resistance exercise reduces bone fragments
Endurance exercises reduce body fat and increase cardiac output and oxygen uptake
Three to five 20 to 60 minute periods of exercise per week to raise heart rate 60% to 90% of maximum
220 bpm minus one’s age in years
Death
Life expectancy - the average length of life in a given population
Has increased substantially over the last century
Male - 76.2 years
Female - 81 years
Life span - maximum age attainable by humans
Has not increased for centuries (maximum age)
No recorded age beyond 122 years
No definable instant of biological death
Some organs function for an hour after the heart stops
Brain death is lack of cerebral activity (flat EEG), reflexes, heartbeat, and respiration for 30 minutes to 24 hours
Normally referred to as death
Brain death does not mean there is no brain activity
A PET scan would not be blank even if someone is dead
Brain dead - no change in electricity
Death usually occurs as a failure of a particular organ followed by a cascade of other organ failures
Homeostasis and Negative Feedback
Homeostasis - maintaining a relatively constant internal environment
Homo - same
Statis - Status
Negative feedback allows for dynamic equilibrium within a limited range around a set point
The response is opposite to the stimulus
Example: when body temperature is too high (stimulus) your body sweats and lowers body temperature (response)
The body uses negative feedback loops
Loss of homeostatic control causes illness or death
Called the disease state
Receptor - structure that senses change in the body
Example: stretch receptors above heart that monitor blood pressure
Normally a sensory organ
Integrating (control) center - control center that processes the sensory information and makes a decision and directs the response
Example: cardiac center of the brain
The central nervous system
Effector - cell or organ that carries out the final corrective action to restore homeostasis
Example: the heart
Normally muscular tissue
Homeostasis depends on the process
Positive Feedback and Rapid Change
Self-amplifying cycle
Leads to greater change in the same direction’
Response is the same as the stimulus
Feedback loop is repeated
Change produces more change
Examples: childbirth, blood clotting, protein digestion, and generation of nerve signals
Contractions lead to more contraction
Can sometimes be dangerous
Example: runaway fever
Gradients and Flow
Gradient - a difference in chemical concentration, charge, temperature, or pressure between 2 points
Matter and energy tend to flow down gradients
Movement in the opposite direction is moving up the gradient
Moving in this direction requires spending metabolic energy
Go from where there is a lot of something to where there is a little
Law of entropy
Moving with the gradient does not require energy
Chemicals flow down concentration gradients
Charged particles flow down electrical gradients
Heat flows down thermal gradients
Cells
Cell Theory
All organisms are composed of cells and cell products
Cell is the simplest structural unit of life
An organism’s structure and functions are due to cell activities
Cells come only from preexisting cells
Cells of all species exhibit biochemical similarities
Different cells have different properties
Example: cell wall
Cell Shapes and Sizes
There are about 200 types of cells in the body with varied shapes
Squamous - thin, flat, scaly
Cuboidal - squarish looking
Can look round, can have rounded corners
Columnar - taller than wide
Can look cuboidal
A cell’s shape can appear different if viewed in a different type of section
Longitudinal vs. cross
Polygonal - irregularly angular shapes, multiple sides
Stellate - star-like
Spheroid to ovoid - round to oval
Discoid - disc-shaped
Fusiform - thick in the middle, tapered toward the ends
Fibrous - thread like
Example: muscles
Human Cell Size
Most cells are about 10-15 micrometers in diameter
Egg cells (very large) are 100 micrometers in diameter
Visible to the naked eye
Some nerve cells are over 1 meter long
Limit on cell size - an overly large cell cannot support itself, may rupture
For a given increase in diameter, volume increases more than surface area
Volume is proportional to cube of diameter
Surface area is proportional to square of diameter
Maximum limit - determined by how quickly something can be moved from the outside to the middle of a cell
Surface area to volume ratio
Comparison of Viewing Techniques
Light microscope (LM) revealed plasma membrane, nucleus, and cytoplasm (fluid between the nucleus and the surface)
Transmission electron microscope (TEM) improved resolution (better detail)
Scanning electron microscope (SEM) improved resolution further, but only for surface features
Can be problematic and easily messed up$
Basic Components of a Cell
Plasma (cell) membrane
Surrounds cell and defines boundaries
Made of proteins and lipids
Cytoplasm - interior of cell
Organelles
Example: nucleus
Cytoskeleton
Inclusions - stored or foreign particles
Cytosol - intercellular fluid (ICF)
Extracellular fluid (ECF) - fluid outside of cells, includes tissue (interstitial fluid)
The Plasma Membrane
The border of the cell
Appears as a pair of dark parallel lines when viewed with an electron microscope
Has intracellular and extracellular faces
Functions: defines cell boundaries, governs interactions with other cells, controls passage of materials in and out of the cell
Has 2 layers of phospholipids
Glycerol head with a partial charge (polar), fatty acid tail (saturated fatty acids) does not have a partial charge (nonpolar)
Maximum number of hydrogens attached to the carbon
Membrane Lipids
98% of membrane molecules are lipids
Phospholipids
75% of membrane lipids are phospholipids
Amphipathic molecules arranged in a bilayer
Amphipathic - has both a polar and nonpolar region
Example: ethanol
Hydrophilic phosphate head faces the water on each side of the membrane
Hydrophobic tails are directed towards the center avoiding the water
Drift laterally, keeping membrane fluid
Cholesterol
20% of the membrane lipids
Holds phospholipids still and can stiffen the membrane
Can change with the temperature
Acclimatize to colder temperatures and lower the amount of cholesterol to maintain viscosity
Glycolipids
5% of the membrane lipids
Phospholipids with short carbohydrate chains on extracellular face
Contributes to glycocalyx - carbohydrate coating on cell surface
A carbohydrate and a lipid
Can identify a person through these and can differentiate where a cell came from
Membrane Proteins
2% of the molecules but 50% if the weight of membrane
Integral proteins penetrate membrane
Transmembrane proteins pass completely through
hydrophobic exterior, hydrophilic interior
Give form and function to the cell membrane
Hydrophilic regions contact cytoplasm (extracellular fluid)
Hydrophobic regions pass through lipid of the membrane
Some drift in the membrane others are stuck to the cytoskeleton
Peripheral proteins
Adhere to one face of the membrane, but do not penetrate
Usually tethered to the cytoskeleton
Proteins make up the majority of dry weight in our bodies
There are not. a lot of proteins in our cell membranes, but proteins are large
Channel proteins - hydrophilic materials go through
Functions of membrane proteins include
Receptors - binds to chemical messengers such as hormones sent by other cells, bind chemical signals
Tell what to change inside a cell
Enzymes - breaks down a chemical messenger and terminates its effect, catalyze reactions including digestion of molecules, and production of second messengers
Organic catalyst
Majority of proteins in the body
Channels - constantly open and allows solutes to pass into and out of the cell, allow hydrophilic solutes and water to pass through the membrane
Gated channel - opens and closes to allow solutes through but only at certain times
Ligand gated channels - respond to chemical messengers
Voltage gated channels - responds to charged particles
Mechanically gated channels - respond to physical stress on cell
Example: cochlea
Cell-identity marker - glycoprotein, distinguishes the body’s own cells from foreign cells, act as identification tags
Cell-adhesion molecule (CAM) - binds cells together, mechanically link cell to extracellular material
Second messenger systems - communicate with cell receiving the chemical message
Carriers - binds solutes and transfers them across the membrane
Example: pumps
Example: LDL causes high cholesterol, HDL tries to lower LDL
Carriers consume ATP
G-Proteins
Take a small extracellular signal and amplify it intracellularly
Chemical first messenger (epinephrine) binds to a surface receptor
Surface receptor changes shape, and initiates chemical reactions inside a cell
cAMP and Ca2+ are common secondary messengers
Up to 60% of drugs work through G proteins and secondary messengers
The Glycocalyx
Fuzzy coat external to the plasma membrane
Carbohydrate moieties of glycoproteins and glycolipids
Unique in everyone but identical twins
Functions
Protection
Immunity to infection
Defense against cancer
Transplant compatibility
Fertilization
Embryonic development
Has many alcohol groups
Need to match glycocalyx for transplant
Microvilli
Extensions of the membrane
1-2 micrometers
Gives 15-40 times more surface area
Best developed in cells specialized in absorption
On some absorptive cells they are very dense and appear as a fringe
Brush boarder
Some microvilli contain actin filaments that are tugged toward the center of a cell to milk absorbed contents into a cell
If you want to improve absorption, raise the rate of diffusion
Cilia
Motile cilia are in the respiratory tract (cleaning), uterine tubes (moving egg), ventricles of the brain, and the ducts of testes
50 to 200 on each cell
Beat in waves sweeping material across a surface in one direction
Cilia beat freely within a saline layer at cell surface
Chloride pumps pump Cl- into ECF
Na+ and H2) follow
Mucus floats on top of the saline layer
Cystic Fibrosis
Hereditary disease in which cells make chloride pumps, but fail to install them in the plasma membrane
Mutation to the chloride ion channel
Fail to create adequate saline layer on the cell surface
Thick mucus plugs pancreatic ducts and respiratory tract
Sticks to cilia
Inadequate digestion of nutrients and absorption of oxygen
Chronic respiratory infections
Life expectancy is 30, used to be in the teens
Gene/editing and therapy has worked
Flagella
Tail of a sperm - the only function flagellum in humans
Whip-like structure with axoneme identical to cilium’s
Much longer than cilium
Stiffened by coarse fibers that support the tail
Movement is undulating, snake-like, corkscrew
No power stroke and recovery strokes
Largest of 3 extensions
Microvilli is the smallest of the three
20x longer than the body of the sperm
Purpose of locomotion
If there is more than one flagellum it is considered mutated and will not be able to reproduce
Pseudopods
Continually changing extensions of the cell that can vary in shape and size
Can be used for cellular locomotion and capturing foreign particles
Pseudo - fake
Pod - foot
Transitory extensions of the cell membrane
Allows for the cell to move and wrap around target particles like bacteria and debris
Membrane Transport
Plasma membrane is selectively permeable
Allowing some things through, but preventing others from passing
Think of a colander
Passive mechanisms require no ATP
Random molecular motion of particles provide necessary energy
Energy neutral
Move down the gradient
Examples: filtration, diffusion, and osmosis
Active mechanisms consume ATP
Active transport and vesicular transport
Moves against the gradient
Moves a chemical from an area with high concentration to an area with low concentration
Carrier-mediated mechanisms use a membrane protein to transport substances across the membrane
Filtration
Type of passive transport
Particles are driven through the membrane by physical pressures
Filtration of water and small solutes through gaps in capillary walls
Depends on small screens
Allows for the delivery of water and nutrients to tissues
Allows for removal of waste from capillaries in the kidneys
Kidneys have extra leaky capillaries because they filter waste
Simple Diffusion
Net movement of particles from a place of high concentration to a place of lower concentration (passive transport)
Examples: perfume, air freshener
Due to constant spontaneous molecular motion
Molecules collide and bounce off of each other
Substances diffuse down their concentration
Does not require a membrane
Substances can diffuse through a membrane if the membrane is permeable to the substance
Temperature influences the rate of diffusion
The hotter the faster because of greater kinetic energy
Molecular weight - larger molecules move slower
Steepness of concentration gradient - more steep, faster rate
Membrane surface area - greater area faster rate
Membrane permeability - higher permeability faster rate
Osmosis
Net flow of water through a selectively permeable membrane
The movement of water across a membrane
Water moves form the side where it is more concentrated to the side where it is less concentrated
Powered by the concentration of a solute that cannot move across the membrane
Water will move across and dipole-dipole bond or hydrogen bond
Examples: sugar on fruit, beef jerky
Solute particles that cannot pass through the membrane “draw” water from the other size
Water moves from higher purity to lower purity
Crucial consideration for IV fluids
Osmotic imbalances underlie diarrhea, constipation and edema
Water can diffuse through phospholipid bilayers, but osmosis is enhanced by aquaporins
Aquaporins - channel proteins in a membrane specialized for water passage
Cells can speed up osmosis by installing more aquaporins
Aqua - water
Porin - whole
Many aquaporins are in the kidneys
Osmotic pressure - the pulling force
Increases as the amount of nonpermeating solute rises
Examples: more salts or proteins
Hydrostatic pressure - the pushing force
Physically increases as fluid presses against the membrane
Example: heart contracting to pump blood
Increases pressure
Reverse osmosis - the process of applying mechanical pressure to override osmotic pressure
Mechanical filtration across a membrane
Push along the membrane
Allows for the purification of water
Water goes to the ionic compounds
Osmotic and hydrostatic are opposite
Osmolarity and Tonicity
One osmole (osm) = 1 mole of dissolved particles
Takes into account whether the solute ionizes in water
Molarity multipled by the number of ions
May need to look at solubility rules
1 M glucose is 1 osm/L
1 M NaCl is 2 osm/L
Osmolarity - the number of osmoles per liter of solution
Body fluids contain a mix of many chemicals, and osmolarity is the total osmotic concentration of all the solutes
Blood plasma, tissue fluid, and intracellular fluid are 300 milliosmole per liter (mOsm/L)
Hypotonic solution - causes a cell to absorb water and swell
Not enough salt (less than 0.9%), cells will absorb a lot of water
Has a lower concentration of nonpermeating solutes than intracellular fluid (ICF)
Distilled water is an extreme example
Hypertonic solution - causes cells to lose water and shrivel (crenate)
Has a higher concentration of nonpermeating solutes than ICF
Too much salt (more than 0.9%) cells will lose water
Isotonic solution - causes no change in cell volume
Concentrations of nonpermeating solutes in bath and ICF are the same
Normal saline (0.9% NaCl) is an example
When osmolarity inside and outside are equal so no net movement of water
Carrier-Mediated Transport
Transport proteins in membrane carry solutes into or out of a cell or organelle
Transport proteins are specific for particular solutes
Solute (ligand) binds to the receptor site on the carrier protein
Solute is released unchanged on the other side of the membrane
As solute concentration rises, the rate of transport rises, but only to a point
Transport maximum (Tm) - the transport rate at which all carriers are occupied
One protein is designed to move one chemical
One chemical per protein
Different proteins can move the same chemical, though some are better at it than others
Saturation maximum - the maximum rate chemicals can be moved
If you increase the number of carrier proteins the transport maximum would increase, opposite if you remove carrier proteins
Example: diabetes
Three kinds of carriers
Uniport - carries one type of solute, moves one molecule at a time
Example: calcium pump
Symport - carries two or more solutes simultaneously in the same direction (cotransport), two in the same direction at the same time
Example: sodium-glucose transporters
Antiport - carries two or more solutes in opposite directions (countertransport)
Usually powered by the direct consumption of ATP
Example: sodium-potasium pump
Removes Na+ and brings in K+
Three kinds of carrier-mediated transport
Facilitated diffusion, primary active transport, and secondary active transport
Most common carrier in the body is uniport
Secondary active transport is powered by the concentration gradient
Facilitated diffusion - the carrier moves the solute down its concentration gradient (passive transport - follows concentration gradient)
Does not consume ATP
The solute attaches to the binding site on the carrier, the carrier changes information, then releases the solute on the other side of the membrane
Passive transport does not use ATP, moves from high concentration to low concentration
Primary active transport - the carrier moves the solute through a membrane up its concentration gradient
ATP is used, consumes energy
Example: calcium pump (uniport) uses ATP while expelling calcium from cell to where it is already more concentrated
Example: sodium-potassium pump (antiport) uses ATP while expelling sodium and importing potassium into the cell (most common)
Directly consumes ATP, though some can consume indirectly as well
Magnifies the gradient - larger difference between extremes
There will be a resting membrane voltage
Sodium-potassium pump functions
Maintains steep Na+ concentration gradient allowing for secondary active transport
Regulates solute concentration and thus osmosis
Maintains negatively charged resting membrane
Produces heat - generates lots of heat
Primary source of body heat
“Burns” through ATP
One of the single biggest energy usages in the body
Uses 40% of calories
Secondary active transport - the carrier moves the solute through the membrane but only uses ATP indirectly
Example: sodium-glucose transporter (SGLT, symport)
In kidneys and digestive track, pulls out glucose and in the body/bloodstream, will eventually be moved against the concentration gradient
Moves glucose into the cell while simultaneously carrying sodium down its gradient
Depends on primary transport performed by Na+ and K+ pump
Does not use ATP itself
Uses concentration gradient of a different ion (normally sodium)
Gradient will want to equalize, can pull other chemicals along with them
SGLTs work in kidney cells that have Na+ and K+ pump at the other end of the cell
Basal surface - primary active transport, high concentration of sodium outside the cell and low concentration inside
Can use the gradient of sodium ions to transport glucose into the cell (secondary active transport)
Vesicular Transport
Moves large particles, fluid droplets, or numerous molecules at once through the membrane in vesicles - bubble like enclosures of membrane
Utilizes motor proteins energized by ATP
Vesicle - storage compartment
Formed when the cell membranes folds in or out on itself
Fold out to get something out of the cell
Exocytosis - discharging material from the cell
Endocytosis - vesicular processes that bring material into the cell
Phagocytosis - “cell eating” engulfing large particles, brings solids into cells
Phag - eat
Pseudopods, phagosomes, and macrophages
Example: white blood cells wrapping around bacteria
Pinocytosis - “cell drinking” taking in droplets of ECF containing molecules that are useful in the cell, brings extracellular liquids into the cell
Pino - drink
The membrane caves in and pinches off pinocytic vesicle
Receptor-mediated endocytosis - particles bind to specific receptors on the plasma membrane
Protein receptors on cells are selectively grabbing specific molecules, concentrate on the surface of the cell, when there is enough it is brought inside the cell
Enables cells to take in specific molecules that bind to extracellular receptors
More selective
Clathrin-coated vescile in cytoplasm - uptakes LDL from the blood stream
How you get high concentrations/amounts of a chemical/protein into a cell
Lybosome - organelle filled with digestive enzymes
Transcytosis - transport of material across the cell by capturing it on one side and releasing it on the other
Receptor-mediated endocytosis moves it into the cell and exocytosis moves it out the other side
trans - across
Chemical is carried from one side of the cell into and through the cell and out the other side
Example: the blood brain barrier
Exocytosis - secrets material, something is released from the cell
Replacement of plasma membrane removed by endocytosis
Phospholipids will fuse with the plasma membrane - increases surface area, endocytosis will remove phospholipids and decrease the surface area
The Cytoskeleton
The network of protein filaments and cylinders
Determines cell shape, supports structure, organizes cell contents, directs movement of materials within a cell, contributes to movements of the cell as a whole
Gives shape and organization to the cell membrane and organelles
Composed of microfilaments, intermediate fibers, and microtubles
Microfilaments - 6 nanometers thick, made from actin protein, forms terminal web
Intermediate filaments - 8-10 nanometers thick, within skin cells, made of keratin protein, gives a cell shape, resists stress
Microtubles - 25 nanometers thick, consist of protofilaments, made of protein tubulin, radiate from centrosome, can come and go, maintain cell shape, hold organelles, act as railroad tracks for walking motor proteins, make axonemes of cilia and flagella, from mitotic spindule, hollowm make cilia
Tube madde of tubes
May have motor proteins build in - dynein and kinesin
Molecular Biology
Essential Cellular Structures
Cell membrane - separates the inside from the outside of the cell
Nucleus - stores DNA
DNA strands are held together with hydrogen bonds
Chromosome - a large piece of tightly coiled DNA
Sister chromatids - identical arms of the same chromosome
Centrosomes - make microtubles
DNA Replication and the Cell Cycle
Before a cell divides it must duplicate its DNA so it can give a complete copy of all of its genes to each daughter cell
Since DNA controls all cellular function this replication process must be very exact
Mistakes can occur
Law of complementary base pairing - we can predict the base sequence of one DNA strand if we know the sequence of the other
A to T
C to G
Strong selective pressures prevent mutation
DNA Replication
Four steps of DNA replication: unwinding, unzipping, building new DNA strands, repackaging
DNA unwinds from histones
DNA helicase unzips a segment of the double helix exposing its nitrogenous bases
Replication fork - the point of DNA opening
Helicase is an enzyme
ends in -ase - enzyme
DNA polymerase builds new DNA strands
Ploymerase reads exposed vases and matches complementary free nucleotides
Separate polymerase molecules and work on each strand proceeding in opposite directions
The polymerase moving toward the replication fork makes a long, continuous, new strand of DNA
Single strand DNA
DNA polymerase builds new DNA strands
DNA polymerase makes polymers of DNA
The polymerase moving away from the replication fork makes short segments of DNA, DNA ligase joins them together
Two daughter DNA molecules are made from the original parental DNA
Semiconservative replication - each daughter DNA consists of one old and one new helix
Half new and half the original parent strand
Newly made DNA is repackaged
With thousands of polymerase molecules working simultaneously on the DNA, all 46 chromosomes are replicated in 6-8 hours
Millions of histones are made in the cytoplasm while DNA is replicated and they are transported into the nucleus soon after DNA replication ends
Each new DNA helix wraps around histones to make new nucleosomes
Looks for mutations and fixes them
Mitochondrial genome is replicated faster
Chloroplast in plants is replicated quickly
Errors and Mutations
DNA polymerase makes mistakes
Multiple modes for correction of replication errors
double checks the new base pair and tends to replace biochemically unstable pairs with more stable correct pairs
Result is only one error per 1 billion bases replicated
Mutations - changes in DNA structure due to replication errors or environmental factors - radiation, viruses, chemicals
Some mutations cause no ill effects, others can kill the cell, turn it cancerous, or cause genetic defects in future genreations
DNA is the densest, most replicated, and have the most information storage in the universe
The Cell Cycle
The cell’s life form one division to the next
Includes interphase and the mitotic phase
Interphase includes 3 subspaces
G1, S, G2
Mitotic phase includes multiple subspaces
Prophase, metaphase, anaphase, telophase
Mitotic phase - the replication phase
Synthesis - doubles DNA
G1 Phase - the first gap phase
Interval between cell birth (from division) and DNA replication
Cell carries out normal tasks and accumulates materials for the next phase
Gathering building blocks
S phase - synthesis phase
Cell replicates all nuclear DNA and duplicates centrioles
Synthesis, genome is replicated
G2 phase - second gap phase
Interval between DNA replication and cell division
Cell repairs DNA replication errors, grows and synthesizes enzymes that control cell division
Quality control, looks for mistakes
M phase - mitotic phase
Cell replicates its nucleus
Pinches in two to form new daughter cells
G0 phase - describes cells that have left the cycle and cease dividing for a long time or permanently
Do not get replicated, focuses on forming necessary functions
Examples: motor neurons, skeletal muscle tissue, stasis
Cell cycle duration varies between cell types
Mitosis
A main goal is to take one cell with two copies of the genome (diploid = 2n) and make two identical daughter cells which are also diploid
A diploid has 2 sets of chromosomes
The division of the nucleus
Functions: growth of all tissues and organs after birth, replacement of cells that can die, repair of damaged tissue
Four phases: prophase, metaphase, anaphase, telophase
Somatic cells - non sex-cells, majority of the cells in the body
For cellular reproduction - growing, tissues repair (normal skin and inside the digestive track)
Prophase - genetic material condenses into compact chromosomes
Start of mitosis
Makes it easier to distribute to daughter cells than chromatin
46 chromosomes - 2 chromatids per chromosome
DNA condenses into chromosomes
Mitotic spindles form
Nuclear envelope disintegrates
Centrioles sprout spindle fibers - long microtubles
Spindle fibers push centriole pairs apart
Some spindle fibers attach to kinetorches of centromeres of chromosomes
Metaphase - chromosomes are aligned on the cell equator
Chromosomes are lined up in the middle of the cell
Spindle fibers complete mitotic spindle (lemon shaped)
Spindles attach to chromosomes
Shorter microtubles from centrioles complete and aster which anchors itself to the inside of the cell membrane
Anaphase - enzyme cleaves two sister chromatids apart at centromere
Chromosomes are ripped in half by mitotic spindles to form 2 unreplicated chromosomes
Single stranded daughter chromosomes migrate to each both of the cell as motor proteins in kinetochores crawl along spindle fibers
Telophase - chromosomes cluster on each side of the cell
Rough ER makes a new nuclear envelope around each cluster
ER makes phospholipids
Phospholipids are needed to make the double membrane around the nuclei
Chromosomes uncoil to chromatin
Mitotic spindle disintegrates
Each nucleus forms a nucleoli
Have gradual transition between phases
Cytokinesis - the division of the cytoplasm into two cells
Telophase is the end of nuclear division but overlaps cytokinesis
Cytokinesis begins during telophase
Activated by myosin protein pulling on actin in the terminal web of cytoskeleton
Creates a cleavage furrow around the equator of the cell
Shows the start of cytokinesis
The cell eventually pinches into two - ends with 2 diploid daughter cells
Meiosis - when sperm and egg cells are made, only have haploid daughter cells
Regulation of Cell Division
Cells divide when:
They have enough cytoplasm for two daughter cells
They have replicated their DNA
They have adequate supply of nutrients
They are stimulated by growth factors - chemical signals
Neighboring cells die, opening ups space
Cells stop dividing when:
They snugly contact neighboring cells
Nutrients or growth factors are withdrawn
Occurs so we don’t get cancer - if the cell cycle is not working correctly a tumor can form
Molecular timer
Cyclins - proteins that regulate the cell cycle, common target for cancer research
Not normally present but form during interphase
Cyclin-dependent kinases (cdks) - activated by cyclins to phosphorylate other proteins
Cyclin-cdk complexes control
The replication of DNA and centrioles in the S phase
The condensation of chromosomes, breakdown of nuclear envelope, formation of the mitotic spindle, and attachment of chromosomes to the spindle in prophase
The splitting of the centromere and separation of the sister chromatids at anaphase
Checkpoints are controlled by cyclin-cdk complexes
Start or G1 checkpoint - either allows the cell to proceed toward the S phase, or if it doesn’t the cell goes into the noncycling G0 phase
Checks if there are enough nutrients
G2/M check point - late in the G2 phase, determines whether the cell is able to proceed to mitosis
A third checkpoint at the transition from metaphase to anaphase determines whether the cell can proceed to anaphase, leading to separation its sister chromatids
DNA is checked
What is a Gene?
Gene - an information containing segment of DNA that codes for the production of a molecule of RNA that plays a role in synthesizing one or more proteins
Amino acid sequence of a protein is determined by the nucleotide sequence in the DNA
There are thousands of genes in a chromosome
Genome - all the DNA in one 23-chromosome set
All of the genes combined
3.1 billion nucleotide pairs in the human genome
46 human chromosomes, come in two sets of 23 chromosomes
Diploid = 2n
One set of 23 chromosomes come from each parent
The Genetic Code
The body can make millions of different proteins (the proteome) from just 20 amino acids, and encoded by genes made of just 4 nucleotide (A, T, C, G)
Genetic code - a system that enables the 4 nucleotides to code for amino acid sequences of all proteins
Amino acids are the building blocks of protein
Minimum code to symbolize 20 amino acids is three nucleotides per amino acid
Base triplet - a sequence of 3 DNA nucleotides that stands for one amino acid
3 nucleotides per amino acid
Codon - the 3-base sequence in mRNA
DNA to RNA to protein
DNA has T-thyminr
RNA has U-uracil
AUG (methanine) is the start amino acid
Protein Synthesis
All body cells except sex cells and some immune cells contain identical genes
Immune cells specifically plasma cells differ (shuffled genome)
Different genes are activated in different cells
Sometimes genes are activated and sometimes not
Can change the type of cell
Any given cell uses 1/3 to 2/3 of its genes
The rest remain dormant and may be functional in other types of cells
Involves the genome
The shape of an antibody determines which pathogens it can and cannot attach to
When a gene is activated messenger RNA (mRNA) is made
mRNA is complementary to the gene
Migrates from the nucleus to the cytoplasm where it codes for amino acids
Process of protein synthesis DNA to mRNA to protein
In transcription DNA codes for mRNA - occurs in the nucleus
mRNA is made in the nucleus
Copies information, stays in the language of nucleic acid
In translation mRNA codes for the protein - usually occurs in the cytoplasm
Translation - one language to another, nucleic acid to amino acid
Chemical code to a different chemical code
Ribosomes translate genetic code
Transcription
The copying of genetic instructions from DNA to mRNA
RNA polymerase - an enzyme that binds to DNA and assembles mRNA
Certain DNA base sequences signal start
RNA polymerase opens up the DNA helix and reads the bases from one strand of DNA
Helicase is what opens up the DNA helix
Simple base signals
Makes corresponding DNA
C on DNA - G on mRNA
G on DNA - C on mRNA
T on DNA - A on mRNA
A on DNA - U on mRNA
If a region of DNA does not actively code for RNA it doesn’t mean that it doesn’t hav e function
Example: regulatory DNA
RNA polymerase rewinds the DNA helix behind it
A gene can be transcribed by several polymerase molecules
Terminator - a base sequence at the end of a gene signaling to stop
Pre-mRNA - immature RNA produced by transcription
Gets edited in the nucleus
Exons - segments of pre-mRNA that will be exported from the nucleus and translated into protein
Introns - segments of pre-mRNA that must be removed before translation, stay inside the nucleus
Most likely used in the control of protein synthesis
Introns are broken down into nucleotide monomers and recycled for new mRNA sequences
Enzymes within the nucleus remove introns from the RNA and splice exons together
One gene can produce one pre-mRNA to give 6 variations of glucose transporter protein
One gene will code for multiple variations of the same protein - called mRNA editing
Alternative splicing - variations in the way exons are spliced allow for a variety of proteins to be produced from one gene
One gene can code for more than one protein
Exons can be spliced together into a variety of different mRNAS
Translation
The process that converts the language of nucleotides into the language of amino acids
Go from mRNA to proteins
Occurs in the cytoplasm
Three main participants in translation
mRNA carries code form the nucleus to the cytoplasm
Has a protein cap that is a recognition site for ribosome
Physically carries the information
Transfer RNA (tRNA) - delivers a single amino acid to the ribosome for it to be added to the growing protein chain
Contains an anticodon - a series of 3 nucleotides that are complementary to the codon of mRNA
Have 1 amino acid attached to them, delivers one amino acid at a time to the growing protein
Ribosomes - organelles that read the message
Found free in cytosol, rough on ER and on nuclear envelope
Consist of large and small subunits where each subunit is made of several enzymes and ribosomal RNA (rRNA) molecules
Nonmembrane bound organelle made of RNA for protein synthesis
mRNA molecules begins with the leader sequence
Acts as a binding site for a small ribosomal subunit
Large subunit attaches to a small subunit
Ribosome pulls a mRNA molecule through it like a ribbon reading the bases as it goes
Ribosome slides around to find AUG
When the start codon (AUG, methionine) is reached, protein synthesis begins
All proteins begin with methionine when first synthesized
Three steps to translation: initiation, elongation, termination
Initiation: the leader sequence in mRNA binds to the small ribosomal subunit, the initiator tRNA (bearing methionine) pairs with the start codon, the large ribosomal subunit joins the complex and the now fully formed ribosome begins reading bases
mRNA exits the nucleus and forms a ring and ribosomal subunits attach and find AUG, collects the amino acids to start the protein, continues with other amino acids until the stop codon
Elongation: the next tRNA (with its amino acid) binds to the ribosome while its anticodon pairs with the next codon of mRNA, peptide bond forms between methionine and second amino acid, ribosome slides to read the next codon and releases initiator tRNA (empty), next tRNA with appropriate anticodon brings its amino acid to the ribosome, another peptide bond forms between the second and third amino acids, the process repeats extending a peptide to a protein
Termination: when the ribosome reaches a stop codon a release factor binds to it, finished protein breaks away from the ribosome, ribosome dissociates into 2 subunits
3 different stop codons: UAA, UAG, UGA
Translation can be rapid
Polyribosome - 1 mRNA attached to multiple ribosomes, usually 10-20
A cell may have 300,000 identical mRNA molecules undergoing simultaneous translation
A cell can produce over 100,000 protein molecules per second
Individual ribosomes synthesize individual proteins
Transfer RNA
Small RNA molecule
Coils on itself to form an angular L shape
One end includes 3 nucleotides called an anticodon
Other end has a binding site specific for one amino acid
tRNA picks up a free amino acid in cytosol
The cost of binding an amino acid to the tRNA is 1 ATP
1 tRNA for each individual codon
Protein Processing and Secretion
Protein synthesis is not finished when the amino acid sequence (primary structure) has been assembled
To work a protein must fold into precise secondary and tertiary structures
Chaperone proteins - older proteins that pick up new proteins and guide their folding into the proper shapes
Proteins to be used in the cytosol are likely to be made on free ribosomes within the cytosol
Cytosol - the liquid in the cytoplasm, stays in the cell
Proteins destined for packaging into lysosomes or secretion from the cell are assembled on rough ER and sent to the Golgi complex for packaging
Entire polyribosomes migrate to the rough ER and docks on it surface
Assembled amino acid chain completed on rough ER
Sent to Golgi for final modification
Ribosome or rough ER goes to the Golgi complex, becomes an organelle or is excreted
Where a protein is synthesized determines where it goes
Proteins assembled on ER surface threads itself through a porte in the ER membrane into cisterna
ER modifies protein by post-translational modification
Pinches off bubble-like transport vesicle coated with clathrin
Vesicles detach from ER and carry protein to the nearest cisterna of the Golgi complex
Vesicles fuse and unload proteins into Golgi cisterna
Golgi complex further modifies the protein
Some Golgi vesicles become lysosomes
Other Golgi vesicles become secretory vesicles and migrate to the plasma membrane, fuse to it, and release their cell product by exocytosis
Different containers in the Golgi vesicles have different chemical properties and modify more
Gene Regulation
Genes can be turned on and off
Cells can turn some genes permanently off
Example: liver cells turn off hemoglobin genes
Cells can turn genes on only when needed
Depends on environmental factors
Example: bulking vs cuting
The level of gene expression can vary from day to day or hour to hour
Babies are born with blue eyes and they darken
This can be controlled by chemical messengers such as hormones
Examples: mammary gland cells turn on gene for casein protein only when breast milk is produced
Prolactin is amplified intracellularly
In the nucleus prolactin up-regulates transcription of the casein
Binds to ribosomes in the golgi complex
Casein - most prominent in milk, selectively turning on a gene
Synthesizing Compounds Other Than Proteins
Cells synthesize glycogen, fat, steroids, phospholipids, pigments, and other compounds
There are no genes for these products, but their synthesis is under indirect genetic control
They are produced by enzymatic reactions
Enzymes are proteins encoded by genes
Example: production of testosterone (a steroid)
A cell of the testes takes in cholesterol
Enzymatically converts it to testosterone
Only occurs when genes for the enzyme are active
Genes may greatly affect such complex outcomes as behavior, aggression, and sex drive
Less than 50% of dry weight is not protein
Enzymes are made from protein, and are used to make molecules
Molecules are synthesized by other proteins in the body
Theories of Senescence
Senescence may be an intrinsic process governed by the inevitable or even programmed changes in cell function
Intrinsic process - built in system
Senescence may be due to extrinsic (environmental) factors that progressively damage our cells over a lifetime
There is evidence that heredity plays a role
Twin studies of life span
Genetic conditions of progeria (werner syndrome)
Senescence - the loss of function of something
Lose functions to organ system
Example: skin gets thinner
Can swap old cells with new cells, but as we age that stops happening
The rate we age at is by both nature and nurture (genetic and environmental)
Nature - progeria, twins
Twins - one lives longer depending on environmental risks
Replicative senescence: decline in mitotic potential with age
Organ function depends on cell renewal keeping pace with cell death, but human cells can only divide a limited number of times
Telomeres - the ends of the chromosomes that diminish with each division
Some nucleotides are lost during DNA synthesis
Daughter strands are shorter
Get shorter, but coding regions are not affected until telomeres are reached, where genetic information will be lost
In old age, exhaustion of telomeres may make chromosomes more vulnerable to damage and replication errors
Old cells may be increasingly dysfunctional because of this
Counter: somatic cells (sperm and egg)
Enzymes can rebuild telomeres - only in gonads, not in epithelial cells
DNA damage theory: DNA suffers thousands of damaging events per day
Exposed to more environmental factors as you live longer
Examples: cellular replication and ultraviolet light
Oxidative stresses from free radicals generated by metabolism
While most damages are repaired, some persist and accumulate as the cell change, especially in non-dividing cells
Cumulative damage impairs function
Mutations build up and cause cancer
Cross-linking: with age collagen molecules become cross-linked making fibers less soluble and stiff
1/4 of the body’s protein is collagen - most common in the body
Causes stiffness of the joints, lenses, and arteries
Blood vessels - harder to respond to blood pressure changes
Digestive system - harder to move food around
Cross-linking of DNA and enzymes could impair function
Other protein abnormalities: increasingly abnormal structure in older tissues and cells
Lie in changes in protein shape and the moieties that are attached
Cells accumulate more abnormal proteins with age
Example: alzheimer’s - build up abnormal proteins build up and become pathogenic
Autoimmune theory: some altered macromolecules (example: oddly folded proteins) may be recognized as foreign
May stimulate lymphocytes to mount an immune response against the body’s own tissue
Autoimmune diseases become more common with age
Inappropriately up-regulated - antibodies attach to things that belong in the body
Examples: arthritis, chrons
Counter: measles causes immune memory loss
Cellular Respiration: Carbohydrate Metabolism
ATP comes from more that just carbohydrates
Metabolism
All reactions that involve transformations
Any chemical reactions that occur in the body
2 categories
Catabolism - breaks down molecules and releases energy
Example: cat breaks down a sofa by scratching, becomes smaller pieces
Anabolism - makes larger molecules and requires energy
Example: anabolic steroids
All the sugar in our body is from a dietary source
Storage or immediate use
Elevated glucose - insulin, lowers blood sugar, moves glucose to skeletal muscle fibers, get stuck in muscle fibers
Glucose builds in the liver and gets used to raise blood sugar, needs to go from the bloodstream to the inside of the cells (in the cytoplasm)
Cell Respiration
The specific chemical reactions used to turn food into Adenosine Triphosphate (ATP)
The reverse is photosynthesis
The vast majority of plant life uses this
Three main steps: glycolysis, citric acid cycle (kerb’s cycle, TCA cycle), electron transport chain
Steps 2 and 3 occur in the mitochondria
Electron Carriers
Small molecules that serve to carry high energy electrons away from an enzyme
Coenzymes
NAD+ and FADH+ are two electron transporters
Electron carriers are vitamins
Vitamins are organic molecules
Minerals are elements
Electron carriers do not catalyze the reaction, they synthesize with a larger protein
Wheelbarrow analogy - carriers are wheelbarrows, electron is placed into a wheelbarrow, carries it over, dumps it, and returns and puts a new electron into the wheelbarrow, repeats
Can be reused over and over
Glycolysis
The primary purpose is to break glucose molecule into smaller pieces that can go into the mitochondria
Catabolic chemical reaction
Needs to be small enough to fit into the mitochondria
Metabolic pathway
Kickstarted by adding ATP, raises to an unstable configuration (higher energy state)
Glucose to 2 pyruvic acids
One glucose split into 2 pyruvic acids, 3 carbons in each
Net yield of 2 ATP
Exergonic
Example: striking a match on sandpaper
Does not require oxygen and occurs in the cytosol
Net equation: glucose + 2NAP + 2ADP +2Pi —> 2 pyruvic acid + 2NADH + 2ATP
Aerobic vs. Anaerobic
Aerobic respiration - the series of biochemical pathways used when oxygen is present
Makes more ATP
Anaerobic respiration - the series os biochemical pathways used when oxygen is not present
Makes less ATP
If there is some oxygen present, but not enough anaerobic respiration will be used
Oxygen pulls electrons towards itself
Strong electron affinity/electronegativity, strong electron acceptor
Electron carrier brings electrons to oxygen
Anaerobic Fermentation
The fate of pyruvate depends on oxygen availability
In the absence of oxygen (or mitochondria) cells can only generate ATP through glycolysis
Glycolysis cannot continue with a supply of NAD+
Anaerobic fermentation - NAD+ donates electrons to pyruvate reducing it to lactate and regenerating NAD+
Lactate leaves the cells that generate it and travel to the liver via the blood
When oxygen becomes available the liver oxidizes it back to pyruvate
Oxygen deficit - the oxygen required for this is part of the reason we breathe more vigorously after exercising (postexercise oxygen consumption)
Prevents acidosis - blood is too acidic
Example: recovering after running, huffing and puffing, oxygen is brought to the liver to remove lactic acid, turns back into pyruvic acid to complete cellular respiration
The liver can also convert lactate back to G6P and polymerize it to form glycogen for storage
Can also remove the phosphate group and release free glucose into the blood
Drawbacks of anaerobic fermentation: wasteful because most of the energy of glucose is still in the lactate and has contributed no useful work, lactate is toxic
Skeletal muscle is relatively tolerant of anaerobic fermentation, cardiac muscle less so, the brain employs no anaerobic fermentation
Glycogen - the storage molecule for glucose, pulled from when blood sugar is low
This is why athletes do carbo crams, to have extra glucose to tap into
The more intermediate species, the more energy we lost to thermal waste
We rely on some of this to maintain body temperature
Skeletal muscle experiences oxygen deficit more than any other type of muscle in the body
Aerobic Respiration
Pyruvic acid enters the mitochondria
CO2 is removed, Coenzyme A forms acetyl CoA
Pyruvic acid itself is not capable of getting past the mitochondria’s double membrane
The functional group is taken off and carbon dioxide is made
Acetyl CoA can enter the citric acid cycle
The goal is to make as much ATP possible from glucose
There are carbons lost into carbon dioxide
3 carbons, 3 carbon dioxide molecules
Circular series of reactions
Citric Acid Cycle
The primary purpose is to collect high energy electrons for the electron transport chain
This takes place in the mitochondrial matrix (liquid on the far inside of the mitochondrion)
Acetyl CoA combines with oxaloacetic acid to form citric acid
A series of reactions to convert citric acid back to oxaloacetic acid
The mitochondria’s folding in on itself is important for the electron transport chain
Adds 2 carbons to the electron transport chain
Citric acid is the start of the citric acid cycle
Loss of 2 CO2, gain of 2 C, electrons removed, net yield of 1 ATP
GTP is too reactive/unstable, gets added to ADP to make ATP
Electron Transport Chain and Oxidative Phosphorylation
Primary purpose is to make ATP
For 1 glucose there are 2 rotations through the cycle because there are 2 pyruvic acids and each enters the citric acid cycle phosphorylating ADP
Where something is phosphorylated a phosphate is added (PO4)-3
Takes place inside the mitochondria on the folds of the inner membrane (cristae)
A linked series of proteins on the cristae will transport high energy electrons between them
NADH+ and FADH2 carry electrons to ETC
High energy electrons are transported through different proteins
Electrons are shuttled in sequence through ETC
NAD+ and FAD+ are regenerated
Energy is used to phosphorylate ADP to make ATP
Energy is lost from electrons during electron transport
Goes from electron states and is used to move protons against the concentration gradient
Cyanide breaks the electron transport chain
Forces through anaerobic fermentation even though oxygen is present
Making ATP produces a byproduct of water
Free energy decreases
Cyanide binds to iron atom in one of the ETC proteins
Prevents electrons from moving and stops the system
Prevents the production of ATP through aerobic pathways
ETC pumps protons into the intermembrane space
Protons turn ATP synthase
ATP Synthesis Overview
ATP can be made 2 ways
Direct (substrate-level)
Both ATPs in glycolysis are made this way
2 ATPs/glucose in CAC are made this way
Oxidative phosphorylation
ATP generated by ETC
30-32 ATPs/glucose made this way
Total - 32-34 ATP per glucose (net yield)
Glycogen Metabolism
ATP is quickly used after it is formed
It is an energy transfer molecule not an energy storage molecule
The body converts extra glucose to other compounds better suited for energy storage (glycogen and fat)
Glycogenesis - synthesis of glycogen
Medium term of energy storage
Stimulated by insulin
Chains glucose monomers together
Genesis - creation of
Goes from glucose to glycogen
Glycogenolysis - hydrolysis of glycogen
Releases glucose between meals
Stimulated by glucagon and epinephrine
Liver cells can release glucose back into blood
Gluconeogenesis - synthesis of glucose from non-carbohydrates, such as glycerol and amino acids
Occurs only in the liver and later in the kidneys if necessary
Glycogen back to glucose
Neo - new