Block 1 Exam Flashcards
General physiolgy
Focus on the cellular principles that are common to the function of all organs and tissues
Comparative physiology
Focuses on differences and similarities among different species
Medical physiology
Deals with how the human body functions
Requires integrated understanding of events at the level of molecules, cells, and organs
Milieu exterieur
surrounds the whole organism
Milieu interieur
Tissues and cells of the organisms live in here
Extracellular fluid
What can released molecules initiate?
Signal transduction to modify gene transcription and a wide range of other cell functions
Fixte du milieu interieur
Free independent life
Homeostasis
Control of a vital parameter
Negative feedback mechanism requirements
Sense vital parameter
Compare input signal with set point
Multiply error signal by proportionality factor
Output signal activates effector mechanism
Physiology
study of homeostatic mechanisms that allow an organism to persist despite ever-changing pressures of environment
5 Constituents of the cytoplasm
myriad proteins nucleic acids nucleotides synthesized sugars accumulated sugars
Plasma membrane
Forms cell’s outer skin
Permeability of plasma membrane
Impermeable to large molecules
Selectively permeable to small molecules
Active transport
Use metabolic energy to drive uphill movements of substances
Principle constituents of cellular membrane
Lipid and proteins
Head groupd
Identity determines name as well as properties of phospholipids
Phosphatidylethanolamines
Ethanolamine in head group
Phospholipid characteristics at low concentrations
Monolayer
Hydrophilic head groups are fully dissolved
Hydrophobic tails stick up in the air
Phospholipid characteristics at medium concentrations
Micelles
Headgroups form surfaces of small spheres
Tails point toward their centers
Phospholipid characteristics at high concentrations
Bilayers
Arrange into two parallel sheets facing each other tail to tail
Leaflets
Why can detergents dissolve phospholipid membranes
Both are amphipathic
Sol state
High temperatures: thermal energy is greater than interaction energy
Lateral diffusion is rapid
Gel state
Lower temperatures: interaction energy is greater than thermal energy
Lateral diffusion is slow
Transition temperature
Bilayer membrane converts from the gel to the sol phase (and vice versa)
Sphingomyelins
Sphingolipids because they contain sphingosine
Phospholipids because they contain a phosphate group
Why is the rate of “flip-flop” low for phospholipids?
Hydrophilic head group would have to transit central hydrophobic core
Movement of phospholipids
Move side to side, flex, and rotate
Inner surface of plasma membrane
Phosphatidylethanolamine and phosphatidylserine
Outer surface of plasma membrane
Almost exclusively phosphatidycholine
Membrane microdomains
Caveolae
Caveolins
Rafts
Caveolae
Flask shaped invaginations of plasma membrane
Cavolins
Proteins making up the coat for caveolae
Rafts
Defined by biochemical behaviors of constituents when surrounding membrane is dissolved in nonionic detergents
Peripherally associated membrane proteins
Adhere to cytoplasmic or extracellular surfaces
Can be removed by very high salt concentration or very low salt concentration
What disrupts ionic bonds in peripherally associated membrane proteins
Very high salt concentrations
What disrupts hydrogen bonds in peripherally associated membrane proteins
Very low salt concentrations
Integral membrane proteins
Intimately associate with lipid bilayer
Membrane must be dissolved to dislodge
What are the possible integral membrane protein associations
Transmembrane
Embedded in bilayer
Lipid-anchored proteins
Transmembrane proteins
Span the lipid bilayer
Embedded proteins
Doesn’t cross the bilayer
Lipid-anchored proteins
Attached by covalent bond or fatty-acid derivative
Membrane spanning a-helices
Short stretches of aa that pass through membrane once
Mainly non-polar aa
Topology
Pattern with which the transmembrane protein weaves across lipid bilayer
Multimeric proteins
Membrane proteins form tight, noncovalent associations with other membrane proteins in plane of bilayer
Increase stability
Ligand-binding receptors
Comprise group of transmembrane proteins that most clearly illustrate concept of transmembrane signaling
Adhesion molecules
Form physical contacts with surrounding EC matrix or with the cellular neighbors
Integrins
Comprise large family of transmembrane proteins that link cells to EC matrix
Cell-cell adhesion molecules
Attach cells to each other
Cadherins
Glycoproteins with one membrane spanning segment and a large extracellular domain that binds Ca2+
N-CAMs
Neural cell adhesion molecules
Members of immunoglobulin superfamily
GPI-linked class
Linked to membrane phospholipids via an oligosaccharide
Effect of loss of cell-cell and cell-matrix adhesions
Hallmark characteristic of metastatic tumor cells
Pores and channels
Allow water, specific ions, very large proteins to flow passively through bilayer
Carriers
Facilitate transport of specific molecule across membrane
Couple transport of a molecule to that of other solutes
Pumps
Use energy released by ATP hydrolysis to drive transport of substances into or out of the cells against energy gradients
Amphipathic helices
Hydrophobic aa alternate with hydrophilic aa at regular intervals
Nuclear pores
Penetrate nuclear envelope and provide transport between cytoplasm and nuclear interior
Chromatin
Complex between DNA and DNA-binding proteins
Nucleosomes
Chain of tightly folded DNA-protein assemblies
Proton pumps
Embedded within lysosome’s limiting membrane
Aids in protein hydrolysis
Endocytic vesicle
Surrounds material that has been internalized from cell exterior by endocytosis
Tubulin
Heterodimers form microtubules
Plus end vs minus end
Heterodimers can be added at 3x speed at the plus end
Centrosome
Microtubule-organizing center
Basal body
Centriole situated at ciliary root
Cilia
Present on surface of epithelial cells
Radial spokes
Connect outer tubules to central pair
What do Muscle heavy chains consist of?
The N-terminal head
A neck, lever, linker, or hinge
C-terminal rod or tail
Kinesins
Hydrolyze ATP and convert this energy into mechanical transitions causing kinesins to walk along microtubule
Cytoplasmic dynein
Moves in plus to minus direction (retrograde)
Thin filaments
Helical polymers composed of globular actin (G-actin)
How are thin filaments functionally similar to microtubules?
Actin polymers are polar and grow at different rates at each end
Actin binds and then hydrolyzes a nucleotide
Thick filaments
Composed of dimers of myosin
Myosin
Helical tails and globular head groups
Hydrolyze ATP at head group
What family are myosin molecules in muscles a part of?
Myosin II
Cell locomotion
Arrays of actin-myosin filaments are responsible
Growth cone
Tip of growing axon
Richly endowed with contractile fibers
Capable of same motions that characterize motile cells
Amino-terminal extensions
Present on most secretory or membrane proteins
Never on soluble proteins in cytosol
Signal-recognition particle (SRP)
Ribonucleoprotein complex
7 distinct polypeptides
Translation arrest
Protein synthesis is stopped
Persists until SRP-nascent peptide-ribosome complex finds unoccupied docking protein
Translocon
Contains tunnel or nascent protein to pass through across rough ER membrane
Glycosylation
Enzymatic, en-bloc coupling of preassembled oligosaccharide chains to asparagine residues
Protein disulfide isomerase
Catalyzes disulfide bond formation
Enzyme retained in the ER lumen through noncovalent interactions with ER membrane proteins
Tertiary structure
Folding of the protein
Chaperones
Large class of ATP-hydrolyzing proteins that appear to participate in wide variety of polypeptide-folding phenomena
Unfolded protein response activation mechanisms
Feedback control
Cell fate regulation
Adaptive response
Feedback control
Regulating rate of protein synthesis by temporarily halting protein translation
Cell fate regulation
Recognizing and eliminating misfolded proteins
Adaptive response
Ramping up production of molecular chaperones involved in protein folding
Ubiquitin
Marks proteins for destruction
Retrotranslocation
Removes ubiquitin-tagged proteins from ER membrane
Proteasome
Degrades ubiquitinated proteins
Secretory pathway
Rout followed by all secretory and membrane proteins
Porosomes
Universal secretory machinery in cells
Coatamer
Involved in trafficking of proteins between ER and Golgi and between stacks of the Golgi
How do coatamer coats differ from clathrin cages?
Coatamer coats are composed of several coatamer proteins
Clathrin cages formation is spontaneous, coatamer coat assembly requires ATP
Coatamer coat remains until vesicle docks with target membrane
SNAREs
Receptors for SNAPs
Calnexin and Calreticulin
ER proteins that retain misfolded proteins until they are folded properly or degraded
Trans-Golgi Network (TGN)
Sorts proteins
Tunicamycin
Blocks addition of N-linked sugars to newly synthesized proteins preventing M6P recognition markers from attaching
Fluid phase endocytosis
Uptake of materials dissolved in ECF and not bound to receptors on cell surface
Receptor-mediated endocytosis
Molecules bind to cell-surface receptors with high affinity
Familial hypercholesterolemia (FHC)
Caused by defect in gene encoding LDL receptor
Features of epithelia
Connect to one another via tight junctions
Tight junctions define boundary between apical and basolateral domain
Central cilium
Sense mechanical deformation associated with fluid flow
Tight junction
Complex structure impedes passage of molecules and ions between cells of epithelial monolayer
Claudins
Principal structural elements of tight junction
Roles of tight junctions
Barriers
Selective gates
Fences
Tight junction barriers
Separate one compartment from another
Tight junction selective gates
Permit certain solutes to flow easier than others
Tight junction fences
Separate polarized surfaces of epithelial plasm into apical and basolateral domains
What information do epithelial cells need
Must know which end is up
Must know there are neighbors to establish cell-cell contacts
Gap junctions
Interconnect cytosols of neighboring cells
Desmosomes
Holds adjacent cells together at a single, round spot
What are the four types of extracellular signaling molecules
Amines
Peptides and proteins
Steroids
Other small molecules
Five categories of receptor
Ligand-gated ion channels G proteins-coupled receptors Catalytic receptors Nuclear receptors Receptors that undergo clevage
Six steps of signaling
Recognition Transduction Transmission Modulation Response Termination
Gs
Stimulates adenylyl cyclase
Gi
Inhibits adenylyl cyclase
Families of GTP-binding proteins
Ras Rho Rab Arf Ran
Ras proteins
Regulate gene transcription
Rho proteins
Rearrangement of cytoskeleton
Rab and Arf proteins
Vesicle trafficking
Ran proteins
Nucleocytoplasmic transport
Which step of gene expression is most commonly regulated?
Step 2 Initiation of transcription
How is chromatin remodeling regulated?
Histone acetylation
DNA methylation
How is initiation of transcription regulated?
Transcriptional activation or repression
How is termination of transcription regulated?
Premature termination
How is RNA processing regulated?
Alternative splicing
How is nucleocytoplasmic transport regulated?
Blockade of transport
How is translation regulated?
Control of translation
How is mRNA degradation regulated?
mRNA stability
What mediates splicing?
snRNPs
What are snRNPs?
Complex of proteins and snRNA
Ligand-gated ion channels Ligand or Agonist
Small organic molecules, neurotransmitters
Ligand-gated ion channels receptor location
Membrane bound
Ligand-gated ion channels receptor subunit structure
Multimer
Ligand-gated ion channels receptor-ligand affinity
Low
Ligand-gated ion channels Receptor function
Ion channel opens or closes
Ligand-gated ion channels termination of signal
Diffusion from cleft
Degradative enzymes
Presynaptic neuron reuptake
Nuclear receptor ligand or agonist
Contains hydrophobic AAs or sterol nucleus
Nuclear receptor location
Cytoplasm (bonded to chaperone)
Nucleus
Nuclear receptor subunit structure
Intracellular soluble protein
Nuclear receptor function
Transcription Factors
Importance of Promoter region in DNA
Basal Transcription Machinery Assembles
Importance of TATA box in DNA
TFIID binds and anchors Pol II
Importance of 5’ Flanking Regions in DNA
Contains enhancers and suppressor sequences
Importance of Introns and Exons in DNA
Transcribed
What parts of DNA are included in the transcript?
Introns and Exons
Importance of 7-methyl guanosine cap in RNA
Add to mRNA transcript and is required for export out of nucleus
Importance of Introns in RNA
Translated or spliced out (siRNA or miRNA)
Importance of Exons in RNA
Translated or spliced out
Importance of Poly A tail in RNA
Adds stability to mRNA
Importance of 5’ UTR in RNA
Location for ribosome to sit prior to translating mRNA
Types of Seizures
General onset seizure
Focal onset seizure
General Onset and Focal Onset Seizure motor symptoms
Jerking movements (clonic)
Weak/limp muscles (atonic)
Brief muscle twitch (myoclonus)
Tense/rigid muscles (tonic)
General onset seizure non-motor symptoms
Atypical absence seizures (staring spells)
Brief myoclonus in a specific body part/eyelids
Focal Onset Seizure non-motor symptoms
Changes in sensation/emotion
Changes in thinking/cognition
Changes in autonomous function
Lack of movement
General onset seizure
Global seizure in the brain
Focal onset seizure
Specific part of the brain
Main excitatory neurotransmitter in the brain
Glutamate
Main inhibitory neurotransmitter in the brain
GABA
Hyperfunction of iGluRs diseases/disorders
Alzheimer's disease Parkinson's disease Stroked induced ischemic injuries Depression Epilepsy Intellectual disability
Hypofunction of iGluRs diseases/disorders
Epilepsy
Intellectual disability
Schizophrenia
Excitatory receptor ion channel
Na+
K+
Ca2+
Inhibitory receptor ion chanel
Cl-
Misfolded protein in Alzheimer’s Disease
A-beta
Tau
Misfolded protein in Parkinson’s disease
alpha-Synuclein
Misfolded protein in Lewy-body dementia
alpha-Synuclein
Misfolded protein in Huntington’s disease
Huntingtin
Misfolded protein in Amyotropic lateral sclerosis
Superoxide dismutase
FUS
Misfolded protein in Frontotemporal dementia
Tau
TDP-43
Misfolded protein in Spongiform encephalopathies (prion diseases)
Prion protein
What causes Insulin Resistance?
Genes Gender Adiposity Diet Exercise Hyperglycemia Drugs Infection
Osmolality
of particles free in solution/kg solvent (unit= Osm)
Osmolarity
of particles free in solution/unit volume of solvent
Effective osmolyte
a nonpermeant solute that drives movement of water
Tonicity
effective osmolality, doesn’t count permeants, determines whether water will shift compartments (more specific than osmolarity)
Bulk Electroneutrality
of negative charges = # of positive charges in solution
Osmotic pressure
Pressure created by osmotic gradient that drives the movement of water
Oncotic Pressure
Type of osmotic pressure that is generated due to proteins within the plasma
Hydrostatic Pressure
Pressure exerted by a stationary fluid (P=(rho)gh)
Nernst Equation
Ex = (60/z)*log([X]o/[X]i)
Units: mV
Na+ Interstitium concentration
145 mM
K+ Interstitium concentration
4.5 mM
Ca2+ Interstitium concentration
1.2 mM
Cl- Interstitium concentration
116 mM
Na+ Intracellular concentration
15 mM
K+ Intracellular concentration
120 mM
Ca2+ Intracellular concentration
10^-7 M
Cl- Intracellular concentration
20 mM
Driving Force equation
Vm - Ex
Where does Mfn1 bind
Outer mitochondrial membrane
Where does OPA1 bind
Inner mitochondrial membrane
What is DRP1’s receptor
Fis1
Na+ Plasma Concentration
142 mM
Na+ Protein-free plasma concentration
153 mM
K+ Plasma concentration
4.4
K+ Protein-free plasma concentration
4.7 mM
Ca2+ Plasma concentration
- 2 mM (ionized)
2. 4 mM (total)
Ca2+ Protein-free Plasma concentration
1.3 mM (ionized)
Cl- Plasma concentration
102 mM
Cl- Protein-free plasma concentration
110 mM
Intracellular osmolality
290 mOsm
ECF osmolality
290 mOsm
Plasma osmolality
291 mOsm
Plasma and interstitial fluid pH
7.4
Cellular pH
7.2
Primary active transport
Energy from ATP hydrolysis coupled to “uphill” movement
Ex: Na+/K+ ATPase
Secondary active transport
Energy from existing gradients coupled to “uphill” movement
Ex: Na+/Ca2+ exchange
Passive transport
Simple diffusion (through lipid bilayer) Facilitated diffusion (specialized transport proteins)
Na+ Equilibrium potential
+61 mV
K+ Equilibrium potential
-88 mV
Ca2+ Equilibrium potential
+125 mV
Cl- Equilibrium potential
-47 mV
Na+ Driving Force
-121 mV
IN
K+ Driving Force
+28 mV
OUT
Ca2+ Driving Force
-185 mV
IN
Cl- Driving Force
-13 mV
OUT
Current and conductance
Ik = Gk * (Vm - Ek)
Parallel Batteries Model
Vm = G’naEna + G’kEk
G’na
Gna/(Gna+Gk)
G’k
Gk/(Gna+Gk)
Troponin T
Binds a single molecule of tropomyosin
Troponin C
Binds Ca2+
Troponin I
Binds actin and inhibits contraction
