Comp Exam-White Flashcards
signal transduction
cell to cell communication
signal transduction pathway interruption example with leptin
knockout of leptin gene → mouse gains weight
leptin is released from fat and signals hypothalamus that you are full
endocrine signaling
long distance signaling
freely diffusible signals
long lasting (long half-life in minutes) → takes time to go through the circulatory system to find a target cell
paracrine signaling
acts locally
affects cells nearby (not as freely diffusible)
short lived sigal
syanptic signaling
acts locally
affects cells nearby (not as freely diffusible)
short lived signal
e.g. neurotransmitters
autocrine signaling:
- cells respond to signal that they themselves release, or release to cells of the ____ type
- cell secretes signal that feeds back and binds to a receptor on its own ____
- e.g. ____ ____ in cancer cells
- same
- surface
- growth factors
direct cell signaling:
- e.g. ____ cells
- ____-presenting cells to ____ cells
- immune
- Ag, T
most ligands or hormones are ____ or ____ and can’t get into a cell
they require ____ mediated signaling
hydrophilic or large
receptor
G-proteins are heterotrimeric proteins composed of 3 subunits:
G-proteins are ____ nucleotide-binding proteins
alpha, beta, gamma
guanine
G-protein signaling
ligand binds → activated receptor binds to G-protein (acts as a GEF) → G-alpha releases GDP and binds GTP and dissociates from G-beta/gamma → G-alpha binds and activates adenylyl cyclase → G-alpha hydrolyzes GTP to GDP, dissociates from adenylyl cyclase and binds back to G-beta/gamme (becoming inactive) → adenylyl cyclase generates cAMP from ATP → cAMP acts as second messenger molecule
cholera and G-protein signaling:
cholera toxin modifies G protein by keeping the G-alpha in the GTP active form indefinitely
pathway is always active
pumps Cl- and water out of cell in intestine and causes severe diarrhea
cAMP targets:
- cAMP activates cAMP-dependent ____ that consists of 4 subunits
- inactive PKA: 2 ____ subunits and 2 ____ subunits
- binding of 2 cAMP molecules to ____ subunits of tetramer results in release of active catalytic subunits
- active catalytic subunits can regulate proteins by addition of ____ group: addition of 2 negative charges can change conformation of protein
- can result in ____ or ____ of enzymatic target proteins
- PKA
- catalytic, regulatory
- regulatory
- phosphate
- activation or inactivation
receptor tyrosine kinases:
- enzymatic domain is in the ____ tail of the integral membrane protein
- are used for response to ____ factors
- ligand binding induces ____ of 2 receptor monomers
- ____ occurs (cross phosphorylation)
- receptor acts as a ____ site to recruit other proteins
- binds to ____ with ____ domain (src homology)
- Grb2 has a ____ domain that binds to ____ in ____
- SOS binds to ____ and acts as a GEF (GDP → GTP)
- Ras → ____ → ____ → ____
- ultimate response: changes in protein activity or gene expression
- cytoplasmic
- growth
- dimerization
- autophosphorylation
- docking
- Grb2, SH2
- SH3, prolines, SOS
- RAS
- Raf → Mek → Erk
receptor tyrosine kinase signaling
- ligand binds and induces dimerization
- autophosphorylation occurs
- docking site
- Grb2 binds (with SH2 domain)
- SH3 domain of Grb2 binds prolines in SOS
- SOS is a GEF and adds GTP to Ras
- Raf → Mek → Erk
- ultimate response
JAK-STAT Receptors:
- ligand binds and receptors ____ , then bind ____ (Janus kinases)
- JAKs ____ each other and the receptor
- receptor binds and phosphorylates ____.
- STATs separate from receptors, ____ , and enters the ____ , binds to ____ and causes transcription
- dimerize, JAKs
- phosphorylate
- STATs
- dimerize, nucleus, DNA
serine-threonine receptor and Smad:
- ligands bind and receptors ____ and are phosphorylated
- activated receptor (by phosphorylation) binds to ____ and phosphorylates ____
- R-smad binds to ____ and moves into nucleus to impact ____
- dimerize
- R-smad, r-smad
- Co-Smad, transcription
what makes cells different
differences in proteins due to differences in gene expression
Helix-turn-helix DNA binding motif:
- ____ DNA binding motif
- ____ alpha helices connected by short chain of amino acids
- longer helix portion = ____ module-DNA
- binds to ____ groove of DNA
- binds DNA as ____
- simplest
- 2
- recognition
- major
- dimer
zinc finger motif:
- DNA binding motif includes a ____ atom
- binds to ____ groove of DNA
- includes ____ and ____ secondary structures
- zinc
- major
- alpha-helix and beta-sheet
leucine zipper motif:
- 3 domains:
- includes:
- interactions between hydrophobic amino acid side chains (leucines) at every ____ amino acids down one side of alpha helix
- grabs DNA like ____
- dimerization domain, activation domain, and DNA binding domain
- 2 alpha helices
- 7
- clothespin
helix-loop-helix motif:
- includes:
- can occur as ____ or ____
- 3 domains:
- short alpha chain connected by a loop to a second longer alpha chain
- homodimers or heterodimers
- DNA binding domain, dimerization domain, activation domain
regulation by RNA stability:
- decapping: exposed mRNA degraded from ____ end
- mRNA degraded from ____ end through polyA tail and into coding region
- 5’
- 3’
3 post translational modifications
non-covalent interactions (protein folding and cofactor binding)
covalent modification (phosphorylation, etc.)
binding to other protein subunits
proteasome:
specificity of proteasome: ____ E1 ubiquitin activating enzyme and ____ proteasome, but 30 E2 ubiquitin conjugating enzymes and hundreds of E3 accessory proteins
apparatus that deliberately destroys aberrant protein
1, 1
cell cycle checkpoints:
- checkpoint 1: ____ checkpoint → cell commits to cell cycle entry and chromosome ____
- is ____ favorable?
- checkpoint 2: ____ checkpoint → move into chromosome alignment on spindle in metaphase
- is all DNA ____ ?
- checkpoint 3: ____ transition → trigger sister chromatid separation and cytokinesis
- Start (G1/S) → duplication
- environment
- G2/M →
- replicated
- metaphase-to-anaphase transition
Cdks:
- ____ of Cdks rise and fall during cell cycle
- there are proteins that regulate Cdks called ____
- ____ levels vary according to the point of time in cell cycle
- activities
- cyclins
- cyclin
cyclin-Cdk activity:
- without cyclin bound (inactive state), the active site of Cdk is blocked by a region called the ____
- the binding of cylcin causes the T-loop to move out of the active site (Cdk is now partly ____ )
- phosphorylation of Cdk by ____ at the T-loop fully activates the cave site of Cdk to make a fully functional Cdk
- ____ phosphorylates roof site (inhibitory)
- ____ dephosphorylates roof site (active)
- T-loop
- active
- CAK
- Wee1
- Cdc25 phosphatase
M-Cdk activates APC/C to complete mitosis:
- M-Cdk + inactive ____ + Cdc20 → active ____
- active APC/C dissociates ____ from securin
- active separase can cleave ____ allowing sister chromatids to separte in anaphase
- APC/C, APC/C
- separase
- cohesin
classes of caspases:
- __caspases synthesized first as an inactive precursor called ____
- ____ caspases activate executioner caspases
- ____ caspases executes apoptosis
- procaspases
- initiator
- executioner
intrinsic pathway of apoptosis:
when ____ is released from mitochondria, it binds to a protein called ____ and forms ____
cytochrome c
Apaf1
apoptosome
BH123
form aggregation in mitochondrial outer membrane and induce release of cytochrome c
Bcl2
blocks intrinsic pathway of apoptosis by binding to BH123 and preventing aggregation
BH3-only protein
activates intrinsic pathway of apoptosis by binding to Bcl2 protein, preventing Bcl2 from binding to BH123
IAPs
block caspases after spontaneous activation of caspases
anti-IAPs
bind to IAPs and activates intrinsic pathway of apoptosis
two broad types of mutations in cancer:
- overactivity mutations: ____ of function - ____ - involves a single mutation event and activation of gene causing propliferation (dominant)
- underactivity mutations: ____ of function - suppressor genes - involve genes that inhibit growth
- mutation event: one gene - no effect, second mutation causes problems ( ____ )
- gain, oncogenes
- loss
- recessive
activatino of oncogenes (4 ways)
- deletion or point mutation in coding sequence → hyperactive protein made in normal amounts
- regulatory mutation → normal protein greatly overproduced
- gene amplification → normal protein greatly overproduced
- chromosome rearrangement → nearby regulatory DNA sequence causes normal protein to be overproduced
- OR fusion to actively transcribed gene produces hyperactive fusion protein
tumor supressor genes:
- tumor supressor genes generally encode proteins that ____ cell proliferation
- 2 major categories of tumor supressor genes
- proteins that normally ____ cell growth and proliferation
- proteins that maintain ____ of the genome
- inhibit
- restrict
- integrity
- restrict
two forms of retinoblastoma
- 40% of retinoblastoma is ____ in which both eyes are affected (tumors)
- somatic event occurs - eliminated one good copy and ____ forms
- cells are predisposed to cancer, but still have ____ good copy of Rb gene
- loss of function or deletion of one copy of Rb in every cell, because the defect is ____
- loss of ____
- 60& of retinoblastoma is ____ (no family history) (single tumor in one eye)
- two-hit hypothesis: first Rb gene obtains mutation, then need ____ mutation of Rb
- Rb protein is a ____ of the cell cycle
- Rb mutations are ____ , both copies of the gene (alleles) need to be inactive/lost
- familial
- tumor
- one
- inherited
- heterozygosity
- sporadic
- second
- regulator
- recessive
tumor progression: polyp:
- polyp is a precursor of ____ cancer
- slow disease → ____ years to develop
- cut off polyp → ____
- if left along, malignant tumor develops from ____ (polyp)
- important loss is ____ mutation which is a tumor supressor
- 40% of colorectal cancers have point mutation in ____
- 60% of colorectal cancers have in inactivating mutation of ____
- colorectal
- 10
- cure
- adenmoa
- APC
- K-ras
- p53
functions of cytoskeleton:
- represents ____ of the cell
- important in ____ of the cell
- maintains correctly ____ cells
- insures cell are properly structured ____
- bones
- organization
- shaped
- internally
acting filaments
mardi-gras beads
determine the shape of cells surface and are necessary for whole-cell locomotion, secretion, and endocytosis
microtubules
slinky of life
forms tube like structure
determines the positions of membrane-enclosed organelles
directy intracellular transport
intermediate filaments
girders in buildings
provide mechanial strength
strong filament
resists mechanical stress
allows formaiton of hair and fingernails
construction of cytoskeleton: actin:
- actin subunits are used for assembly of actin ____
- forms ____ assemblies of subunits
- self-associate, using a combination of ____ to ____ and ___ to ____ protein contacts
- actin monomers are arranged ____ to ____ to generate polarity
- are ____ and easily bent
- filaments
- helical
- end to end and side to side
- head to tail
- flexible
construction of cytoskeleton: tubulin:
- tubulin subunits are used for formation of ____
- form ____ assemblies of subunits
- self-associate, using a combination of ____ to ____ and ____ to ____ protein contacts
- tubulin is a ____ of a-tubulin and b-tubulin with noncovalent bonds
- both have binding site for ____
- plus end: is ____ growing
- minus end: is ____ growing
- microtubules
- helical
- end to end and side to side
- heterodimer
- GTP
- fast
- slow
function of cytoskeleton: RBCs
- RBCs are ____
- RBCs, once relased from bone marrow, have to make 1/2 million passages in ____
- RBCs must be ____ and strong enough to get through tight capillary spaces
- if RBC cytoskeleton is defective → ____
- leads to ____ ____
- RBCs are ____
- fragile RBCs ____
- ____ anemia
- leads to ____ ____
- protein involved in RBC cytoskeleon:
- bi-concave
- circulation
- flexible
- anemia
- hereditary spherocytosis
- spherical
- burst
- hemolytic
- hereditary spherocytosis
- ankyrin and spectrin
hereditary spherocytosis:
- ____ is defective in this disease
- spherical RBCs that lyse and release ____
- clinical presentation:
- spectrin
- hemoglobin
- hemolysis, anemia, splenomegaly
listeria:
- invades ____ cells
- found in the ____ and found on unwashed ____
- symptoms:
- can cause food ____
- every year about ____ people get infection
- 1/5 patients ____
- especially important during ____
- treatment is with ____
- ____-based motily of listeria causes damage
- intestinal
- soil, lettuce
- headache, stiff neck, confusion, loss of balance, convulsions, fever, muscle aches
- poisoning
- 1600
- die
- pregnancy
- antibiotics
- actin
listeria:
- leaves an ____ track which are comet tails
- ____ complex makes this happen
- addition of actin ____ filaments pushes the bacteria along
- actin
- Arp2/3
- branched
duchenne muscular dystrophy:
- DMD is most common fatal ____ disorder
- patients are in wheelchairs by age ____
- may develop ____
- premature death in 20s to 30s due to ____ failure or ____
- treatment aims to improve ____ of life
- ____ (predinose) has been shown to slow decline but effects are short (18-36 months)
- ____-linked recessive
- starts to show symptoms at ____ years
- ____ cases are familial
- neuromuscular
- 12
- scoliosis
- respiratory failure or cardiac myopathy
- quality
- glucocorticoids
- X
- 3
- 2/3
dystrophin protein:
- largest gene known: ____kDa and ____ exons
- main function is to provide structural stabilty to ____ cell membrane during cycles of contraction/relaxation
- have 4 functional domains
- N-terminal: ____ binding domain
- long spectrin like repeat domain: ____ portion of the dystropin protein
- cysteine rich and C-terminus: binds syntrophin proteins and dystroglycans
- deletion hotspots at exons ____ and ____
- 427, 79
- muscle
- actin
- cytoskeletal
*
- cytoskeletal
- actin
- 3-19 and 42-60
DMD clinical presentaiton:
- elevated ____ kinase in blood: 50-100x greater
- diagnosed about ____ years
- necrosis of muscle fibers occurs with replacement of ____ or ____ tissue
- leads to ____ : replacemnt of muscle with adipose and fibrous connective tissus → enlarged calves
- ____ run/walk
- walk on ____
- ____ : excessive inward curvature
- ____ : upward back curvature forward
- ____ maneuver
- creatine
- 4-5
- fat or connective
- pseudohypertrophy
- waddling
- tiptoes
- lordosis
- kyphosis
- Gower
becker muscular dystrophy:
- ____ form of Duchenne
- loss of walking after ____ years
- increased workload on ____ ventricle leads to enlargement
- ____-linked recessive
- some dystrophin protein - abnormal ____ and ____
- milder
- 16
- left
- X
- size and quantity
mitochondria:
- provides cellular energy in form of ____ for the cell
- does so by ____ and ____ ____
- have their own ____
- contains ____ genes for ____ proteins
- higher incidence of ____
- mitochondrial ____ is a muscle disease caused by mitochondrial dysfunction
- characterstics: clinical ____ and age related progession of disease
- ATP
- ETC and oxidative phosphorylation
- DNA
- 37 genes for 13 proteins
- mutation
- myopathys
- variability
mitochondrial myopathy caused by accumulation of abnormal mitochondria that form aggregates of red sarcolemmal botches called
Ragged Red Fibers
mitochondria:
- ____ inherited - mitochondria in eggs
- if mtDNA mutation occurs: a mixture of normal mitochondria and mutant mitochondria occurs in one cell, this is called ____
- need a certain level of aberrant mitochondria vs normal mitochondria for disease to occur, this is called ____ effect
- what tissues are generally impacted by mitochondrial diseases:
- maternally
- heteroplasmy
- threshold
- tissues that require more energy than others → brain/CNS, heart, and skeletal muscle
MERRF: Myoclonus Epilepsy with Ragged Red Fibers:
- myoclonus → often the ____ symptom
- myoclonic ____
- ____ (lack of coordinated muscle movements)
- ____ ____ ____ (muscle tissue)
- seizures and ____
- first
- epilepsy
- ataxia
- Ragged Red Fibers
- dementia
MELAS: Mitochondrial Encephalopathy, Lactic Acidosis with Stroke-like episodes:
- stroke-like episodes of ____
- blindness
- headaches
- anorexia
- recurrent vomiting
- lactic acidosis
- Ragged Red Fibers
- hemiparesis
Kearnes-Sayre Syndrome:
- onset before age ____
- ____ ____ (degenerative eye disease leading to blindness)
- at least one of the following:
- cardiac ____ abnormality
- cerebellar ____
- ____ spinal protein level above 100 mg/dL
- may have other presentations: optic atrophy, hearing loss, demenia, seizures, cardiomyopathy, lactic acidosis
- ____ ____ ____ are seen in skeletal muscles
- 20
- retinitis pigmentosa
- conduction
- ataxia
- cerebral
- conduction
- Ragged Red Fibers
CPEO: Chronic Progressive External Ophthalmoplegia:
- mild to moderate mitochondrial myopathy (ragged red fibers oserved in skeletal muscle) - mtDNA ____
- ____
- rearrangements
- ptosis
Leber Hereditary Optic Neuropathy (LHON):
- mitochondrial mutation only affects ____ nerve
- no ____ involvement
- acute or subacute, bilateral, loss of ____ vision
- degeneration of retinal ____ cell layer and optic nerve
- age of onset: ____ to ____
- onset and progression is ____
- initially affects ____ eye but eventually ____ are affected
- If a male has LHON, ____ percent chance that their offspring sill have LHON (unless mother has it)
- not caused by tRNA or mtDNA rearrangement, but mutations affect mtDNA genes encoding complex 1 ____ → single base pair substitutions
- optic
- muscle
- central
- ganglion
- 20s to 30s
- rapid
- one, both
- 0
- proteins
