Principles of Physiology Exam 1

Krogh's principle

for every biological problem there is an organism on which it can be most conveniently studied

Bergman's rule

larger species will be found in colder climates; species of smaller sizes will be found in warmer climates

Body Size and Complexity

complexity increases with body size to increase internal surface area ratio

Basal Metabolic Rate (BMR)

metabolic rate when organism is at rest (energy needed for vital processes)

Mass-Specific Metabolic Rate (MSMR)

BMR divided by organism's mass

BMR vs Mass

allometric relationship- nonlinear correspondence between BMR and mass

Surface Area and Volume

SA:V ratio gets smaller as volume increases at much faster rate than surface area; having more SA means higher rate of exchange across cell membrane

Pros and Cons of being large

Pros: maintains body temp more easily, have more inert tissue, greater cell specialization
Cons: move slower, more easily targeted by predators, require carefully maintained environment

Homeostasis

maintained via negative feedback loops; equilibrium state

Conformers

organisms where homeostasis is heavily influenced by environment

Avoiders

organism where homeostasis avoid environmental conditions

Regulators

organisms where homeostasis is mid affected

Negative Feedback Loops

Give signals to return to systems to norman/baseline, most common, lots of subtypes
Antagonistic: usually to effectors with opposite effects
Anticipatory: activates corrective response before variable is disturbed (ex. glucose and insulin, thermostat, body temperature)

Feedback Loop terms

Stimulus: initiation event
Variable: effect
Sensor: detects the change in the variable
Integrator: compares against reference value (set point)
Effectors: make adjustments to the variable

Positive Feedback Loops

work to enhance or continue change, rare
(ex. labor, fight and flight)

Nucleotides

DNA/RNA, ATP/NADH
DNA/RNA Structure: phosphate group, pentose sugar (deoxyribose), nitrogenous base
ATP: 3 phosphate groups, adenine, ribose
NADH: same thing lol

Proteins

Functional: enzymes, transport, channels
Signaling: millions of signaling molecules and receptors
Immunity: antibodies
Energy storage: protein catabolism
Structural: microtubules and other filaments
20 different amino acids: categorized into polar charges, polar uncharged, nonpolar (hydrophobic)

Levels of Protein Structure

Primary: sequence of amino acids
Secondary: hydrogen bonds, alpha helices, beta sheets
Tertiary: noncovalent bonds, just folding
Quaternary: multiple subunits together

Heat Shock and Protein Damage

Proteins unfold/misfold at high temperatures
Heat shock-proteins interact with other proteins to help them fold correctly

Carbohydrates

Sugars in single units or chain
Energy Storage (glucose): packed together and stored as starch or glycogen
Structural (cellulose chitin)
Signaling (glycoproteins glycolipids): cell adhesion and recognition (ABO blood types), digestion (absorptive surface)

Lipids

Fatty acids, triglycerides, phospholipids, cholesterol
All are hydrophobic: nonpolar C-H bonds, need help travelling through blood
Energy storage: long-term storage (fatty acids, triglycerides)
Structural/functional (cell membranes)
Has to be transported as triglyceride (glycerol plus fatty acids)
Saturated vs Unsaturated fatty acids
Structure of phospholipids: polar head face out and nonpolar fatty acid tails face inward
Steroids: derived from cholesterol through a series of enzymatic modifications, easily diffuse across cell membranes to bind to intracellular receptors

Central Dogma

Allele of gene transcribed into RNA containing exons and introns that go through exon splicing to get mRNA that is translated into a protein by a ribosome and tRNA

Glycolysis

1. spend 1 ATP to trap glucose in the cell (hexokinase takes glucose and makes glucose 6-phosphate)
2. rearrange it to prepare for split
3. spend 1 ATP add a P prepare split
4. splits into 3 carbon molecules [glyceraldehyde-3-phosphate]
5. interacts NAD + Pi to create NADH + H+ to add extra phosphate G-3-P (2x)
6. two P groups transferred to ADP to make 2 ATP (2x) -> 2 pyruvate

Input and Output of Glycolysis

Input: 2 ATP, glucose, NADPi
Output: 4 ATP, 2 pyruvate, 2 NADH, H2O
Net ATP: 2

Linking Step

Pyruvate to Acetate
1. move pyruvate from cytosol to mitochondria (gain NADH, convert pyruvate to Acetyl-CoA)
2. pyruvate travels through transmembrane protein, releases CO2, protonate an NAD to NADH, and is tagged with Coenzyme A to produce Acetyl-CoA

Citric Acid/Krebs Cycle

1. Acetyl-CoA combines with oxaloacetate and water via Citrate synthase to create Citrate and CoA-SH (makes the 3 C Acetyl-CoA a 6 C Citrate)
2. Energy-harvesting steps produce: 3 NADH + FADH2 + ATP (2x) (so in total- 6, 2, 2)
3. overall by this point, 1 glucose molecule has produced: 4 ATP, 10 NADH, 2 FADH2

Anaerobic Respiration

Begins with glycolysis, but pyruvate interacts with lactate dehydrogenase to convert it into lactate; makes less energy but at a faster pace

Electron Transport Chain (Oxidative Phosphorylation)

1. 10 NADH * 2.5 ATP = 25 ATP
2. 2 FADH2 * 1.5 ATP = 3 ATP
Net 28 ATP
- proton gradient has high extracellular proton concentration and low intracellular proton concentration; gradient drives ATP synthase
- waste products: oxygen free radicals (oxygen containing unpaired electrons) search for electron to complete and stabilize atom (can be combated via antioxidants)

Where does each step of glucose metabolism take place?

1. glycolysis = cytosol
2. linking step = mitochondrial matrix
3. krebs cycle = mitochondrial matrix
4. ETC = mitochondrial inner membrane

Free Radicals

contain an unpaired electron

Antioxidant

can donate a spare electron

Fat Catabolism

1. Lipolysis: triglycerides broken down into free fatty acids
2. transported into mitochondria- use 2 ATP and CoA to make a fatty Acyl-CoA (activated fatty acid)
3. carnitine replaces CoA so that it can help long-chain fatty acids across mitochondrial membrane (short chains can cross alone)
4. Beta Oxidation: snips off two carbon atoms at a time and sends Acetyl-CoA to citric acid cycle

Protein Catabolism

1. Proteasomes digest chains tagged with ubiquitin
2. newly broken amino acids can go directly into Krebs cycle
- glucogenic, ketogenic, and glucogenic/ketogenic

Nucleic Acid Catabolism

1. glycolysis breaks nucleotides into nucleoside, then separates pentose and base along glycosidic bond
2. purines turn into uric acid
3. pyrimidines turn into citric acid cycle intermediates

Fluid Mosaic

- cell membranes are never static
- CM composed of phospholipid bilayer (hydrophilic head and hydrophobic tail)
- Saturated (no double/triple bonds) v Unsaturated (has "kinks" created by double/triple bonds)
- Membrane fluidity: liquid crystal at high temp, crystal at low temp (can't function properly)
- Fluidity maintained by cholesterol levels and unsaturated fatty acids

Selective Permeability

- Permeable: gasses and lipophilic molecules
- Semipermeable: small uncharged polar molecules
- Impermeable: large uncharged polar molecules, ions

Simple Diffusion

- movement of particles from high to low concentrations without protein, no energy or transporters needed, applies to lipid-soluble molecules, driven by concentration gradient
- Fick's Law: "molar flux due to diffusion is proportional to the concentration gradient"
-Osmosis

Osmosis

-movement of a solvent through a semipermeable membrane to equalize the solute concentration (solvent typically water and solute is molecule)

Osmotic Pressure

- force that must be applied to a solution side to stop movement of water
- hypoosmotic: low osmotic pressure, low # of solutes in cell, water diffuses out
- hyperosmotic: high osmotic pressure, high # of solutes in cell, water diffuses in
- isosmotic: equal osmotic pressure, equal number of solutes, no net movement of water

Osmolarity

a measure of osmotic pressure of a given solution (unit = osmoles)

Tonicity

- same measure as osmolarity BUT only applies to non-permeable solutes; penetrating solutes have NO effect on tonicity
- hypertonic solution has a higher concentration of solutes outside the cell, water leaves and cell shrinks (plasmolysis)
- hypotonic solution has a lower concentration of solutes outside the cell, water rushes in and cell expands (cytolysis)
- isotonic solution has equal concentration outside cell, no net movement of water

Facilitated Diffusion

- no ATP required, moves down concentration gradient, requires carrier protein (channel)
- open channels: allows only select molecule to flow through freely
- gated channels: can open/close in response to various stimuli (voltage, ligand, mechanical)
- carrier proteins allow molecules through via conformational change; types are uniport, symport, and antiport

Active Transport

- protein transporter needed, energy is required, molecule moves against concentration gradient
- primary active transport: uses ATP directly (ex. Na+/K+ ATPase pump)
- secondary active transport: uses ATP indirectly, couples movement of one molecule to movement of second molecule; can take product of one primary AT and use it in secondary AT

Cell Signaling Basics

- Signaling cells: send a signal
- Target cells: receives the signal

Indirect (local and distant) signaling

1. release of chemical messenger from signaling cell
2. transport of messenger to target cell
3. communication of signal to target cell

Water and Lipid Solubility

- Hydrophobic and lipophilic: not water soluble, dissolves in lipids, ex. steroids, can't be stored, need carrier proteins, can diffuse across cell membrane
- Hydrophilic and lipophobic: water soluble, does not dissolve in lipid, ex. proteins, can be stored in vesicles, travels freely in blood, can't cross cell membrane but utilizes surface receptors

Ligand-receptor interactions

- Specificity: receptors bind to only correct shaped ligands
- Agonists: activate receptors
- Antagonists: blocks receptors

Regulation of Response

- can down/up regulate by changing number of receptors on cell (more receptors = more response)
- number of receptors most directly related to intensity of response
- Signal transduction pathways increase (amplify) number of molecules affected

Ligand-Gated ion channels

- ligand binding causes change in receptor shape
- concentration gradient dictates direction

Enzyme-linked receptors

- receptor has single membrane-spanning segment
- intracellular domain has enzymatic activity (ex. tyrosine kinase)
- when ligand binds, catalytic domain starts a cascade of events (ex. phosphorylation)
- MAP Kinase, G-protein coupled receptors

MAP Kinase

- regulates genes involved in cell growth/survival
- abnormal signaling = uncontrolled cell growth (cancer)

G-protein coupled receptors

- protein that spans cell membrane, interacts intracellularly with G-proteins
- contain several membrane spanning segments (domains)
- G-protein named for ability to bind to guanosine nucleotide
- activated second messenger systems

G-protein signaling basics

- composed of alpha, beta, and gamma subunits
- alpha begins inactive with bind to GDP
- ligand binds to receptor, leading to conformational change causing alpha subunit to exchange GDP to GTP
- Alpha dissociates from beta/gamma
- alpha activates downstream enzymes and second messengers
- effector enzyme: targets of G-proteins that produce second messengers

Second Messengers

- (alpha)s stimulates adenylyl cyclase which then catalyzes ATP to cAMP; protein kinase enzymes activated by second messenger and catalyze phosphorylation of other proteins
- (alpha)i inhibits adenylyl cyclase
- (alpha)q stimulates phospholipase C which cleaves PIP2 into diacylglycerol (DAG) and inositol triphosphate (IP3); DAG activates protein kinase C while IP3 binds to calcium channel in ER causing calcium release which activated protein kinase enzymes

Subunit -> Effector Enzyme -> 2nd Messenger

- (alpha)s -> adenylyl cyclase -> cAMP
- (alpha)i -> adenylyl cyclase -> cAMP
- (alpha)q -> phospholipase C -> IP3/calcium & DAG

A cell at rest is ...

- negatively charged (around -70 mV)
- maintained via ion channels and electrochemical gradient

Chemical Gradient

ions flow according to ion concentrations, always high to low

Electrical Gradient

- opposites attract, same repel

Electrical properties of CM

- voltage: separation of charged particles on either side creates potential for electrical flow
- current: the movement of charged particles

Electrochemical gradient

- how cells maintain different ion concentrations inside and outside of cell
- chemical: ions diffuse to lower concentration
- electrical: charges attracted to opposite
- equilibrium potential: equal and opposite, no net flow

Nernst Equation

- calculates voltage necessary to oppose net movement of single ion down concentration gradient
- Ex = (61/z)*log([X] outside/[X] inside)

Goldman Hodgkin Katz (GHK) equation

- calculates equilibrium voltage of membrane with account of all ions
- Em = (61 mV)*log[(Pkout+Pnaout+Pclin)/(Pkin+Pnain+Pclout)]
- potassium has highest permeability (P=1), all others relative to it

Neuron Structures

- Multipolar neuron: many dendritic branches, motor (CNS -> effector), pyramidal, Purkinje
- Bipolar neuron: two main branches, relay (CNS -> CNS)
- Unipolar neuron: one main branch, sensory (receptor -> CNS)

Functional Zones of Neuron

1. signal reception: dendrites and soma; received incoming signals and converts it to change in membrane potential
2. signal integration: axon hillock; signal crosses threshold -> action potential started
3. signal conduction: axon (wrapped in myelin sheath); AP travels down axon, unidirectional
4. signal transmission: axon terminals; neurotransmitters released

Neuron Anatomy

dendrites, cell body (soma), axon hillock, axon, myelin sheath (Schwann cells), synapse

Axon size and conduction speed

- the thicker the diameter of the axon, the faster the potential travels (if get too big, end up becoming limiting)
- the more myelinated the axon is, the faster the potential travels

Myelination

- insulating layer of lipid-rich Schwann cells wrapped around axon of internodes
- glial cells: supportive cells
- nodes of ranvier: areas of exposed axonal membrane
- saltatory conduction: AP leaps from node to node

Membrane potential at rest

- created by electrochemical gradient
- main players: Na+ and K+
- resting MP is -70mV

Membrane potential during an action potential

1. Na+ channels begin to open in reaction to slight positive membrane change, Na+ rushes in cell, more Na+ channels begin to open (keeps going until equilibrium potential of +60mV is reached)
2. Na+ inactivation gates close and K+ channels open, K+ rushes out of cell (keeps going until equilibrium potential of -90mV is reached), excess K+ leaks back out

Action Potential

1. depolarization
2. repolarization
3. hyperpolarization

What affects likelihood of an action potential?

- intensity of initial stimulus
- number and types of stimuli that occur together
- frequency of repeated stimuli
- distance from stimuli to axon
- graded potential

Voltage-gated Na+ channels

- 2 gates: normal gate and inactivation gate
- closed at RMP and opens if threshold potential reached
- inactivation gate begins to close slowly throughout depolarization

Voltage-gated K+ channel

- one gate, stays closed at RMP
- opens slowly once -55 mV reached
- open from peak potential through hyperpolarization

Refractory period

- occurs around hyperpolarization
- absolute: incapable of generating new AP, Na+ channel closes, membrane must repolarize
- relative: more difficult to generate AP but can happen with strong enough signal, some Na+ channels inactive and increased K+ channels open

The Synapse

- signal transmission zone
- synaptic cleft: space between presynaptic and postsynaptic cells
- neuromuscular junction: synapse between a motor neuron and a muscle

Diversity of synaptic transmission

- electrical synapse: common in simple animals, gap junction (direct communication between neurons), fast form of communication, can be bi-directional, postsyn and presyn signal similar, excitatory signals only
- chemical synapse: common in complex animals, slower, unidirectional, postyn signal can be different, excitatory or inhibitory

Neurotransmitter release

1. AP reaches axon terminal and depolarizes membrane
2. voltage-gated Ca2+ channels open and calcium flows
3. calcium influx triggers synaptic vesicles to release neurotransmitter
4. neurotransmitter binds to receptors on target cells; ionotropic channels (ligand gated, neurotransmitter binds directly to channel- ex. glutamate) or metabotropic channels (G-protein coupled, neurotransmitter binds to G-protein which sends intracellular signal messengers to open up channel- ex. GABA)

Types of Transmitters

- inhibitory: cause hyperpolarization, postsynaptic cell less likely to generate AP
- excitatory: cause depolarization, postsynaptic cell more likely to generate AP
- ions: Na+ channels are depolarizing and excitatory, K+ are hyperpolarizing and inhibitory, Cl- are hyperpolarizing and inhibitory

Signal Strength

- influenced by neurotransmitter amount and receptor activity
- release: due to frequency of AP, chich influences Ca2+ concentration
- removal: degradation of synaptic molecules by enzymes, uptake by surrounding cells, or passive diffusion out of synaptic cleft
- receptor activity: density of receptors on postsynaptic cell

Kinesin

- motor protein, serves to move vesicles down the axon and axon terminals

Major Neurotransmitters

- cholinergic (acetylcholine): primarily assc. with parasympathetic NS, neuromuscular junction
- adrenergic (norepinephrine, epinephrine): assc. with sympathetic NS, smooth muscle, heart muscle

Neuromuscular junctions

- specialized synapses
- motor neurons presyn cell with ACh -> postsyn is muscle

Primary cholinergic receptors

- Nicotinic: ion influx, simple ion-gated channel, sodium, excitation, ionotropic
- Muscarinic: excitation and inhibition, g-protein coupled

Adergenic system

- epinephrine and norepinephrine
- neurohormones: can be neurotransmitters at synapses (NE) or travel in blood as hormone (E)
- found in sympathetic NS
- receptors: membrane bound G-protein coupled receptors; have varying affinities for EPI and NOR (beta higher affinity for E, alpha higher affinity for NE)

Common neurotransmitters

adrenaline (E), noradrenaline (NE), acetylcholine (ACh), dopamine, serotonin, glutamate, GABA

Numbers to know

- Resting membrane potential = -70mV
- Eq potential Na+ = +60mV
- Eq potential K+ = -90mV
- Eq potential of Cl- = -65mV
- Eq potential of Ca2+ = +120 mV
- AP threshold = -55 mV

Summation

- EPSP-IPSP Cancellation: excitatory and inhibitory graded potentials cancel each other out
- Spatial Summation: excitatory potentials from many neurons trigger threshold point
- Temporal Summation: many excitatory potentials from one neuron triggers threshold point

Which GPCR alpha subunit does each adrenergic receptor have?

- alpha 1 is Gaq
- alpha 2 is Gai
- alpha B Gas

Tetrodotoxin (TTX)

- binds to and blocks Na+ channels