Comp Exam-White

Question 1

signal transduction

Answer 1

cell to cell communication

Question 2

signal transduction pathway interruption example with leptin

Answer 2

knockout of leptin gene → mouse gains weight

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

Question 3

endocrine signaling

Answer 3

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

Question 4

paracrine signaling

Answer 4

acts locally

affects cells nearby (not as freely diffusible)

short lived sigal

Question 5

syanptic signaling

Answer 5

acts locally

affects cells nearby (not as freely diffusible)

short lived signal

e.g. neurotransmitters

Question 6

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

Answer 6

• same
• surface
• growth factors

Question 7

direct cell signaling:

• e.g. ____ cells
• ____-presenting cells to ____ cells

Answer 7

• immune
• Ag, T

Question 8

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

they require ____ mediated signaling

Answer 8

hydrophilic or large

receptor

Question 9

G-proteins are heterotrimeric proteins composed of 3 subunits:

G-proteins are ____ nucleotide-binding proteins

Answer 9

alpha, beta, gamma

guanine

Question 10

G-protein signaling

Answer 10

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

Question 11

cholera and G-protein signaling:

Answer 11

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

Question 12

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

Answer 12

• PKA
• catalytic, regulatory
• regulatory
  
  • phosphate
  • activation or inactivation

Question 13

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

Answer 13

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

Question 14

receptor tyrosine kinase signaling

Answer 14

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

Question 15

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

Answer 15

1. dimerize, JAKs
2. phosphorylate
3. STATs
4. dimerize, nucleus, DNA

Question 16

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 ____

Answer 16

1. dimerize
2. R-smad, r-smad
3. Co-Smad, transcription

Question 17

what makes cells different

Answer 17

differences in proteins due to differences in gene expression

Question 18

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 ____

Answer 18

• simplest
• 2
• recognition
  
  • major
• dimer

Question 19

zinc finger motif:

• DNA binding motif includes a ____ atom
• binds to ____ groove of DNA
• includes ____ and ____ secondary structures

Answer 19

• zinc
• major
• alpha-helix and beta-sheet

Question 20

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 ____

Answer 20

• dimerization domain, activation domain, and DNA binding domain
• 2 alpha helices
• 7
• clothespin

Question 21

helix-loop-helix motif:

• includes:
• can occur as ____ or ____
• 3 domains:

Answer 21

• short alpha chain connected by a loop to a second longer alpha chain
• homodimers or heterodimers
• DNA binding domain, dimerization domain, activation domain

Question 22

regulation by RNA stability:

• decapping: exposed mRNA degraded from ____ end
• mRNA degraded from ____ end through polyA tail and into coding region

Answer 22

• 5’
• 3’

Question 23

3 post translational modifications

Answer 23

non-covalent interactions (protein folding and cofactor binding)

covalent modification (phosphorylation, etc.)

binding to other protein subunits

Question 24

proteasome:

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

Answer 24

apparatus that deliberately destroys aberrant protein

1, 1

Question 25

_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

Answer 25

1. Start (G₁/S) → duplication 1. environment 2. G₂/M → 1. replicated 3. metaphase-to-anaphase transition

Question 26

_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

Answer 26

1. activities 2. cyclins 3. cyclin

Question 27

_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)

Answer 27

1. T-loop 2. active 3. CAK 4. Wee1 5. Cdc25 phosphatase

Question 28

_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

Answer 28

1. APC/C, APC/C 2. separase 3. cohesin

Question 29

_classes of caspases:_ 1. _​_caspases synthesized first as an inactive precursor called \_\_\_\_ 2. ____ caspases activate executioner caspases 3. ____ caspases executes apoptosis

Answer 29

1. procaspases 2. initiator 3. executioner

Question 30

_intrinsic pathway of apoptosis:_ when ____ is released from mitochondria, it binds to a protein called ____ and forms \_\_\_\_

Answer 30

cytochrome c Apaf1 apoptosome

Question 31

BH123

Answer 31

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

Question 32

Bcl2

Answer 32

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

Question 33

BH3-only protein

Answer 33

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

Question 34

IAPs

Answer 34

block caspases after spontaneous activation of caspases

Question 35

anti-IAPs

Answer 35

bind to IAPs and activates intrinsic pathway of apoptosis

Question 36

_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 ( ____ )

Answer 36

* gain, oncogenes * loss * recessive

Question 37

activatino of oncogenes (4 ways)

Answer 37

* 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

Question 38

_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

Answer 38

* inhibit * * restrict * integrity

Question 39

_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

Answer 39

* familial * tumor * one * inherited * heterozygosity * sporadic * second * regulator * recessive

Question 40

_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 \_\_\_\_

Answer 40

* colorectal * 10 * cure * adenmoa * APC * K-ras * p53

Question 41

functions of cytoskeleton: * represents ____ of the cell * important in ____ of the cell * maintains correctly ____ cells * insures cell are properly structured \_\_\_\_

Answer 41

* bones * organization * shaped * internally

Question 42

acting filaments

Answer 42

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

Question 43

microtubules

Answer 43

slinky of life forms tube like structure determines the positions of membrane-enclosed organelles directy intracellular transport

Question 44

intermediate filaments

Answer 44

girders in buildings provide mechanial strength strong filament resists mechanical stress allows formaiton of hair and fingernails

Question 45

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

Answer 45

* filaments * helical * end to end and side to side * head to tail * flexible

Question 46

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

Answer 46

* microtubules * helical * end to end and side to side * heterodimer * GTP * fast * slow

Question 47

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:

Answer 47

* bi-concave * circulation * flexible * anemia * hereditary spherocytosis * spherical * burst * hemolytic * ankyrin and spectrin

Question 48

hereditary spherocytosis: * ____ is defective in this disease * spherical RBCs that lyse and release \_\_\_\_ * clinical presentation:

Answer 48

* spectrin * hemoglobin * hemolysis, anemia, splenomegaly

Question 49

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

Answer 49

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

Question 50

listeria: * leaves an ____ track which are comet tails * ____ complex makes this happen * addition of actin ____ filaments pushes the bacteria along

Answer 50

* actin * Arp2/3 * branched

Question 51

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

Answer 51

* neuromuscular * 12 * scoliosis * respiratory failure or cardiac myopathy * quality * glucocorticoids * X * 3 * 2/3

Question 52

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 \_\_\_\_

Answer 52

* 427, 79 * muscle * * actin * cytoskeletal * * 3-19 and 42-60

Question 53

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

Answer 53

* creatine * 4-5 * fat or connective * pseudohypertrophy * waddling * tiptoes * lordosis * kyphosis * Gower

Question 54

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 \_\_\_\_

Answer 54

* milder * 16 * left * X * size and quantity

Question 55

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

Answer 55

* ATP * ETC and oxidative phosphorylation * DNA * 37 genes for 13 proteins * mutation * myopathys * variability

Question 56

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

Answer 56

Ragged Red Fibers

Question 57

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:

Answer 57

* maternally * heteroplasmy * threshold * tissues that require more energy than others → brain/CNS, heart, and skeletal muscle

Question 58

MERRF: Myoclonus Epilepsy with Ragged Red Fibers: * myoclonus → often the ____ symptom * myoclonic \_\_\_\_ * ____ (lack of coordinated muscle movements) * ____ \_\_\_\_ ____ (muscle tissue) * seizures and \_\_\_\_

Answer 58

* first * epilepsy * ataxia * Ragged Red Fibers * dementia

Question 59

MELAS: Mitochondrial Encephalopathy, Lactic Acidosis with Stroke-like episodes: * stroke-like episodes of \_\_\_\_ * blindness * headaches * anorexia * recurrent vomiting * lactic acidosis * Ragged Red Fibers

Answer 59

* hemiparesis

Question 60

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

Answer 60

* 20 * retinitis pigmentosa * * conduction * ataxia * cerebral * * Ragged Red Fibers

Question 61

CPEO: Chronic Progressive External Ophthalmoplegia: * mild to moderate mitochondrial myopathy (ragged red fibers oserved in skeletal muscle) - mtDNA \_\_\_\_ * \_\_\_\_

Answer 61

* rearrangements * ptosis

Question 62

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

Answer 62

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