Foundational toolkit week 1

What are the components of a disease script?

who, why, how, what

What are semantic qualifiers?

relevant details about the pathology (unilateral/bilateral, acute/chronic, severe/mild)

What is a schema?

condensing information into chunks to make it easier to remember

What is non-analytic reasoning?

quick, efficient way of thinking dependent on pattern-recognition and rules of thumb

What is analytic reasoning?

working through a case slowly and methodically

What are the steps of a problem-based approach?

create problem list, identify differential diagnoses, make diagnostic plan, make therapeutic plan, make monitoring plan

What is Occam’s Razor?

the most simple solution is most likely correct (but patients may have as many diseases as they want)

What are the categories of self-care?

physical, psychological, emotional, spiritual, personal, professional

What is One Health?

the concept that human, animal, and environmental health are inextricably connected

What are wicked problems?

unique problems that resist quick fixes and long-term solutions and require interdisciplinary collaboration (climate change, world hunger)

What is cytosol?

non-liquid aqueous substance that organelles are suspended in

What is the plasma membrane?

liquid, non-aqueous lipid bilayer with embedded proteins

What are intracellular membranes?

encase organelles and divide cells into different compartments

What is the role of the endoplasmic reticulum (ER)?

exchanges material within a cell

What is the role of the Golgi complex?

exchanges material with the extracellular space

What is the nuclear envelope?

double layered membrane with nuclear pores

What are nuclear pores?

holes in the nuclear envelope for mRNA and proteins to travel in and out of the nucleus

What is inside the nuclear envelope?

chromatin (DNA), nucleoli (RNA), nuclear lamina (intermediate filaments)

What is outside the nuclear envelope?

basket of intermediate filaments that hold the nucleus in place in the cytosol and anchors of other intracellular structures

What is the function of mitochondria?

has inner and outer membranes to generate ATP

What are the components of the cytoskeleton?

microtubules, actin filaments, intermediate filaments

What is the function of microtubules?

mediate intracellular transport, coordinate global cellular events like polarization and division

What is the function of actin filaments?

cortical network of thin filaments that mediate all motile and contractile behavior

What is the function of intermediate filaments?

rigorous network of fibers that follow microtubules, assist cell shape, and provide support for anchoring intracellular structures

What are the molecular components of of a cell?

inorganic molecules, small organic molecules, and macromolecules

What are the inorganic molecules of a cell?

water (70%) and ions (1%)

What are the small organic molecules of a cell?

sugars, fatty acids, amino acids, nucleotides (less than 3%)

What are the macromolecules of a cell?

proteins, nucleic acids (26%)

What are the types of nucleic acids?

DNA and RNA

What are the functions of proteins?

enzymatic catalysis and regulation, transport, storage, motility, structure and support, immune protection, signaling

What are prion diseases?

protein misfolding that propagates and spreads throughout body, transmissible in blood and meat (mad cow disease, scrapies, chronic wasting disease, cruzfelt-jacob’s disease)

What is primary protein structure?

sequence of amino acids bound by peptide bonds with 20 different R groups

What is secondary protein structure?

alpha helices and beta sheets

How are alpha helices structured?

spiral shaped stabilized by intra-chain H bonds with R groups projecting outwards (keratin)

How are beta sheets structured?

antiparallel chains forming sheets with many alanine and glycine groups (silk)

What is tertiary protein structure?

one complete protein chain from N terminus to C terminus, can contain alpha helices and beta sheets (one subunit of hemoglobin)

What is quaternary structure?

multiple protein chains together (complete hemoglobin made of 4 chains)

What is the function of chaperone complexes?

bind to newly translated proteins as they come out of ribosome to ensure correct folding and destroy misfolded proteins

What is a catalyst?

compound that accelerates a chemical reaction by lowering the activation energy but is not consumed or altered and does not change the overall free energy of the reaction

What are the enzyme classes?

oxidoreductases, transferases, hydrolases, lyases, isomerases, ligases

What is the function of oxidoreductases?

transfer electrons (dehydrogenase)

What is the function of transferases?

transfer C, N, S, or P groups (kinase)

What is the function of hydrolases?

add water to cleave bonds (nuclease, protease)

What is the function of lyases?

cleave C-C, C-N, or C-S bonds to make double bonds (decarboxylase)

What is the function of isomerases?

form isomers, same atoms in different configuration (isomerase)

What is the function of ligases?

hydrolysis of ATP to form new bonds (DNA ligase)

What are the functions of enzymes?

extreme specificity to control what reactions occur, couple favorable and unfavorable reactions, regulatory mechanisms to control activity

How do enzymes catalyze reactions?

enzyme-substrate bond may strain bond to be broken to make it easier to break, active site may provide reactive functional groups or stabilizing charges for transition state, use cofactors like NADH, may form unstable covalent bonds with transition state to stabilize it

What are cofactors?

permanently or temporarily attached organic or inorganic molecules that work with enzymes, mostly vitamins and minerals

What is a prosthetic group?

permanently attached to enzyme

What is a coenzyme?

temporarily attached to enzyme and can participate with other enzymes

What is V_max?

mols/minute, maximum velocity of a reaction at saturating substrate concentration, depends on enzyme concentration

What is K_m?

amount of substrate needed to reach half of Vmax, measure of binding affinity, high = weak, low = strong

What is irreversible inhibition?

drug or toxin destroys enzyme

What the types of reversible inhibition?

competitive, non-competitive, uncompetitive

What is competitive inhibition?

Vmax stays the same, Km increases because more substrate is needed to outcompete inhibitor to reach Vmax, product still made

What is non-competitive inhibition?

Vmax decreases, Km stays the same because inhibitor binds after substrate, preventing product from being made

What is uncompetitive inhibition?

Vmax decreases, Km increases because inhibitor can bind either before or after substrate binding, so it can have both competitive and non-competitive effects

What does allosteric mean?

agent binds to non-active site of enzyme and causes conformational change

How is a trypanosome infection treated?

parasite lifecycle dependent on enzyme ODC, administration of irreversible inhibitor destroys it and prevents replication

How are enzyme assays used in clinic?

many enzymes are organ specific, so their presence in blood indicates pathology

What is specific activity?

number of enzyme units per mg protein

What is a standard unit?

amount of enzyme that catalyzes 1umol per min

What are the functions of the plasma membrane?

regulates chemical and macromolecule exchange with environment, mediates cell-cell adhesion and communication, mediates changes in cell shape and size

What are different ways proteins are embedded in membranes?

transmembrane, membrane associated, lipid-linked, protein attached

What are the functions of the membrane embedded proteins?

transporters, anchors, receptors, enzymes, cell-cell recognition, intercellular joinings

What are membrane proteins covered in and why?

sugars, to make cells distinct and recognizable by other cells (immune cells, fertilization)

What are carrier proteins?

open on one side to pick up a molecule, close, open on the other side to release it into/out of the cell

What are channel proteins?

Open and close entirely to let molecules pass freely into/out of the cell

What does uniport mean?

1 molecule travels in 1 direction through a transport protein

What does symport mean?

2 molecules travel in the same direction through a transport protein

What does antiport mean?

2 molecules travel in opposite directions through a transport protein

What does sodium-potassium pump transport?

3Na+ out of the cell, 2K+ into the cell

What does ouabain do?

inhibits sodium-potassium pump by preventing K+ from binding

What is a voltage gated channel?

ion channel opens due change in membrane potential

What is a ligand gated channel?

ion channel opens due to a substrate binding to a ligand either inside or outside the cell

What is a mechanically gated channel?

ion channel opens due to mechanical force, in the ear when cilia bend

Why do action potentials only travel in 1 direction?

after depolarization, potassium channels are still open, allowing K+ to leave cell, and sodium channels are deactivated, but down the axon is still negatively charged so that area can depolarize to carry the action potential

What is the role of Schwann cells?

wrap around axons to create myelin sheath, insulating axon and preventing action potential from diffusing

What are nodes of Ranvier?

gaps between myelin sheaths when depolarization occurs, about 1mm apart

How does an action potential cross the synaptic cleft?

when signal arrives, voltage gated calcium channels open, Ca2+ triggers vesicles with neurotransmitters to fuse with plasma membrane via SNAREs, neurotransmitters bind to ligand-gated ion channels of next neuron, causing next neuron to depolarize

What is the role of peroxisomes?

oxidation of toxic molecules

What is protein sorting?

selective transport of proteins from cytosol to organelles

What is the role of a signal sequence?

part of a protein that binds to translocator to bring it into intended location (ER, nucleus, mitochondria, peroxisomes)

How is protein transport into the nucleus mediated?

gated transport, karyopherin translocator bind to protein being imported and fibrils made of phenylalanine and glycine line nuclear pores

How is protein transport into mitochondria mediated?

transmembrane transport, TOM is translocator of outer membrane, TIM is translocator of inner membrane

How is protein transport into peroxisomes mediated?

transmembrane transport, C-terminal signal sequence

What is Zellweger syndrome?

hereditary disease with empty peroxisomes causing large liver, high blood iron and copper, vision problems

How is protein transport into the ER mediated?

transmembrane transport, import occurs during translation, signal sequence of about 20 hydrophobic amino acids, stop sequence also read by translocator to prevent more from being imported, but ribosome keeps translating and the rest of the protein stays outside the ER

What is glycosylation?

addition of sugars to proteins at asparagine (N-linked) or serine (O-linked) side chains

What is Cystic Fibrosis?

accumulation of misfolded protein needed for Cl- transport causing thick mucous in respiratory and GI tracts