Comp Exam-White Flashcards

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1
Q

signal transduction

A

cell to cell communication

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2
Q

signal transduction pathway interruption example with leptin

A

knockout of leptin gene → mouse gains weight

leptin is released from fat and signals hypothalamus that you are full

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3
Q

endocrine signaling

A

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

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4
Q

paracrine signaling

A

acts locally

affects cells nearby (not as freely diffusible)

short lived sigal

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5
Q

syanptic signaling

A

acts locally

affects cells nearby (not as freely diffusible)

short lived signal

e.g. neurotransmitters

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6
Q

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
A
  • same
  • surface
  • growth factors
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7
Q

direct cell signaling:

  • e.g. ____ cells
  • ____-presenting cells to ____ cells
A
  • immune
  • Ag, T
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8
Q

most ligands or hormones are ____ or ____ and can’t get into a cell

they require ____ mediated signaling

A

hydrophilic or large

receptor

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9
Q

G-proteins are heterotrimeric proteins composed of 3 subunits:

G-proteins are ____ nucleotide-binding proteins

A

alpha, beta, gamma

guanine

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10
Q

G-protein signaling

A

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

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11
Q

cholera and G-protein signaling:

A

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

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12
Q

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
A
  • PKA
  • catalytic, regulatory
  • regulatory
    • phosphate
    • activation or inactivation
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13
Q

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
A
  • cytoplasmic
  • growth
  • dimerization
  • autophosphorylation
  • docking
    • Grb2, SH2
    • SH3, prolines, SOS
    • RAS
    • Raf → Mek → Erk
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14
Q

receptor tyrosine kinase signaling

A
  1. ligand binds and induces dimerization
  2. autophosphorylation occurs
  3. docking site
  4. Grb2 binds (with SH2 domain)
  5. SH3 domain of Grb2 binds prolines in SOS
  6. SOS is a GEF and adds GTP to Ras
  7. Raf → Mek → Erk
  8. ultimate response
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15
Q

JAK-STAT Receptors:

  1. ligand binds and receptors ____ , then bind ____ (Janus kinases)
  2. JAKs ____ each other and the receptor
  3. receptor binds and phosphorylates ____.
  4. STATs separate from receptors, ____ , and enters the ____ , binds to ____ and causes transcription
A
  1. dimerize, JAKs
  2. phosphorylate
  3. STATs
  4. dimerize, nucleus, DNA
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16
Q

serine-threonine receptor and Smad:

  1. ligands bind and receptors ____ and are phosphorylated
  2. activated receptor (by phosphorylation) binds to ____ and phosphorylates ____
  3. R-smad binds to ____ and moves into nucleus to impact ____
A
  1. dimerize
  2. R-smad, r-smad
  3. Co-Smad, transcription
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17
Q

what makes cells different

A

differences in proteins due to differences in gene expression

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18
Q

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 ____
A
  • simplest
  • 2
  • recognition
    • major
  • dimer
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19
Q

zinc finger motif:

  • DNA binding motif includes a ____ atom
  • binds to ____ groove of DNA
  • includes ____ and ____ secondary structures
A
  • zinc
  • major
  • alpha-helix and beta-sheet
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20
Q

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 ____
A
  • dimerization domain, activation domain, and DNA binding domain
  • 2 alpha helices
  • 7
  • clothespin
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21
Q

helix-loop-helix motif:

  • includes:
  • can occur as ____ or ____
  • 3 domains:
A
  • short alpha chain connected by a loop to a second longer alpha chain
  • homodimers or heterodimers
  • DNA binding domain, dimerization domain, activation domain
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22
Q

regulation by RNA stability:

  • decapping: exposed mRNA degraded from ____ end
  • mRNA degraded from ____ end through polyA tail and into coding region
A
  • 5’
  • 3’
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23
Q

3 post translational modifications

A

non-covalent interactions (protein folding and cofactor binding)

covalent modification (phosphorylation, etc.)

binding to other protein subunits

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24
Q

proteasome:

specificity of proteasome: ____ E1 ubiquitin activating enzyme and ____ proteasome, but 30 E2 ubiquitin conjugating enzymes and hundreds of E3 accessory proteins

A

apparatus that deliberately destroys aberrant protein

1, 1

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25
Q

cell cycle checkpoints:

  1. checkpoint 1: ____ checkpoint → cell commits to cell cycle entry and chromosome ____
    1. is ____ favorable?
  2. checkpoint 2: ____ checkpoint → move into chromosome alignment on spindle in metaphase
    1. is all DNA ____ ?
  3. checkpoint 3: ____ transition → trigger sister chromatid separation and cytokinesis
A
  1. Start (G1/S) → duplication
    1. environment
  2. G2/M →
    1. replicated
  3. metaphase-to-anaphase transition
26
Q

Cdks:

  1. ____ of Cdks rise and fall during cell cycle
  2. there are proteins that regulate Cdks called ____
  3. ____ levels vary according to the point of time in cell cycle
A
  1. activities
  2. cyclins
  3. cyclin
27
Q

cyclin-Cdk activity:

  1. without cyclin bound (inactive state), the active site of Cdk is blocked by a region called the ____
  2. the binding of cylcin causes the T-loop to move out of the active site (Cdk is now partly ____ )
  3. phosphorylation of Cdk by ____ at the T-loop fully activates the cave site of Cdk to make a fully functional Cdk
  4. ____ phosphorylates roof site (inhibitory)
  5. ____ dephosphorylates roof site (active)
A
  1. T-loop
  2. active
  3. CAK
  4. Wee1
  5. Cdc25 phosphatase
28
Q

M-Cdk activates APC/C to complete mitosis:

  1. M-Cdk + inactive ____ + Cdc20 → active ____
  2. active APC/C dissociates ____ from securin
  3. active separase can cleave ____ allowing sister chromatids to separte in anaphase
A
  1. APC/C, APC/C
  2. separase
  3. cohesin
29
Q

classes of caspases:

  1. _​_caspases synthesized first as an inactive precursor called ____
  2. ____ caspases activate executioner caspases
  3. ____ caspases executes apoptosis
A
  1. procaspases
  2. initiator
  3. executioner
30
Q

intrinsic pathway of apoptosis:

when ____ is released from mitochondria, it binds to a protein called ____ and forms ____

A

cytochrome c

Apaf1

apoptosome

31
Q

BH123

A

form aggregation in mitochondrial outer membrane and induce release of cytochrome c

32
Q

Bcl2

A

blocks intrinsic pathway of apoptosis by binding to BH123 and preventing aggregation

33
Q

BH3-only protein

A

activates intrinsic pathway of apoptosis by binding to Bcl2 protein, preventing Bcl2 from binding to BH123

34
Q

IAPs

A

block caspases after spontaneous activation of caspases

35
Q

anti-IAPs

A

bind to IAPs and activates intrinsic pathway of apoptosis

36
Q

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 ( ____ )
A
  • gain, oncogenes
  • loss
    • recessive
37
Q

activatino of oncogenes (4 ways)

A
  • 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
38
Q

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
A
  • inhibit
    • restrict
      • integrity
39
Q

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
A
  • familial
    • tumor
    • one
    • inherited
    • heterozygosity
  • sporadic
    • second
  • regulator
  • recessive
40
Q

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 ____
A
  • colorectal
  • 10
  • cure
  • adenmoa
  • APC
  • K-ras
  • p53
41
Q

functions of cytoskeleton:

  • represents ____ of the cell
  • important in ____ of the cell
  • maintains correctly ____ cells
  • insures cell are properly structured ____
A
  • bones
  • organization
  • shaped
  • internally
42
Q

acting filaments

A

mardi-gras beads

determine the shape of cells surface and are necessary for whole-cell locomotion, secretion, and endocytosis

43
Q

microtubules

A

slinky of life

forms tube like structure

determines the positions of membrane-enclosed organelles

directy intracellular transport

44
Q

intermediate filaments

A

girders in buildings

provide mechanial strength

strong filament

resists mechanical stress

allows formaiton of hair and fingernails

45
Q

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
A
  • filaments
  • helical
  • end to end and side to side
  • head to tail
  • flexible
46
Q

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
A
  • microtubules
  • helical
  • end to end and side to side
  • heterodimer
  • GTP
  • fast
  • slow
47
Q

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
  • protein involved in RBC cytoskeleon:
A
  • bi-concave
  • circulation
  • flexible
  • anemia
    • hereditary spherocytosis
      • spherical
      • burst
      • hemolytic
  • ankyrin and spectrin
48
Q

hereditary spherocytosis:

  • ____ is defective in this disease
  • spherical RBCs that lyse and release ____
  • clinical presentation:
A
  • spectrin
  • hemoglobin
  • hemolysis, anemia, splenomegaly
49
Q

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
A
  • intestinal
  • soil, lettuce
  • headache, stiff neck, confusion, loss of balance, convulsions, fever, muscle aches
  • poisoning
  • 1600
  • die
    • pregnancy
  • antibiotics
  • actin
50
Q

listeria:

  • leaves an ____ track which are comet tails
    • ____ complex makes this happen
  • addition of actin ____ filaments pushes the bacteria along
A
  • actin
    • Arp2/3
  • branched
51
Q

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
A
  • neuromuscular
  • 12
  • scoliosis
  • respiratory failure or cardiac myopathy
  • quality
  • glucocorticoids
  • X
  • 3
  • 2/3
52
Q

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 ____
A
  • 427, 79
  • muscle
    • actin
      • cytoskeletal
        *
  • 3-19 and 42-60
53
Q

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
A
  • creatine
  • 4-5
  • fat or connective
    • pseudohypertrophy
  • waddling
  • tiptoes
  • lordosis
  • kyphosis
  • Gower
54
Q

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 ____
A
  • milder
  • 16
  • left
  • X
  • size and quantity
55
Q

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
A
  • ATP
    • ETC and oxidative phosphorylation
  • DNA
    • 37 genes for 13 proteins
    • mutation
  • myopathys
    • variability
56
Q

mitochondrial myopathy caused by accumulation of abnormal mitochondria that form aggregates of red sarcolemmal botches called

A

Ragged Red Fibers

57
Q

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:
A
  • maternally
  • heteroplasmy
  • threshold
  • tissues that require more energy than others → brain/CNS, heart, and skeletal muscle
58
Q

MERRF: Myoclonus Epilepsy with Ragged Red Fibers:

  • myoclonus → often the ____ symptom
  • myoclonic ____
  • ____ (lack of coordinated muscle movements)
  • ____ ____ ____ (muscle tissue)
  • seizures and ____
A
  • first
  • epilepsy
  • ataxia
  • Ragged Red Fibers
  • dementia
59
Q

MELAS: Mitochondrial Encephalopathy, Lactic Acidosis with Stroke-like episodes:

  • stroke-like episodes of ____
  • blindness
  • headaches
  • anorexia
  • recurrent vomiting
  • lactic acidosis
  • Ragged Red Fibers
A
  • hemiparesis
60
Q

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
A
  • 20
  • retinitis pigmentosa
    • conduction
      • ataxia
      • cerebral
    • Ragged Red Fibers
61
Q

CPEO: Chronic Progressive External Ophthalmoplegia:

  • mild to moderate mitochondrial myopathy (ragged red fibers oserved in skeletal muscle) - mtDNA ____
  • ____
A
  • rearrangements
  • ptosis
62
Q

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
A
  • optic
  • muscle
  • central
  • ganglion
  • 20s to 30s
  • rapid
    • one, both
  • 0
  • proteins