Unit 1 Flashcards
(477 cards)
0
Q
membrane glycoproteins are oriented in the ER membrane with their carbs on the ____ side of the membrane
A
lumenal
1
Q
enzyme that attaches carbs to Asn residues in proteins
A
oligosacharyltransferase
2
Q
blood type allele encoding non functional enzyme
A
O
3
Q
glycoprotein component of mucus
A
mucins
4
Q
endoglycosidases remove ___ from glycoproteins
A
carbs
5
Q
site of glycoprotein degradation
A
lysosome
6
Q
carbs attached to proteins Ser and Thr residues are:
A
O linked
7
Q
a function of mucus secretion
A
lubrication, protection from noxious substances
8
Q
O blood group allele relative to A and B
A
recessive
9
Q
protein with oligosaccharides attached
A
glycoprotein
10
Q
diseases caused by defects in proteoglycan degradation
A
mucopolysaccharidoses
11
Q
enzyme that cleaves bonds between sugars
A
glycosidase
12
Q
ABO blood group antigens are oligosaccharide components of glycoproteins and ____
A
glycolipids
13
Q
enzymes that cleave proteins into aa’s
A
proteases
14
Q
membrane glycoproteins are oriented in the plasma membrane with their carbs on the ____ side of the membrane
A
EC
15
Q
linear or branched polymer of sugars
A
polysaccharides
16
Q
encoded by the ABO gene locus
A
glycosyltransferase
17
Q
protects epithelial cells from noxious substances
A
mucins
18
Q
sugar polymer containing a repeating disaccharide
A
glycosaminoglycan
19
Q
Cys residues in mucins allow them to
A
polymerize
20
Q
protein with glycosaminoglycan chains attached
A
proteoglycan
21
Q
individuals with AB blood have alleles that are
A
codominant
22
Q
O linked glycosylation occurs here
A
Golgi
23
Q
individuals with O blood are considered universal ____
A
donors
24
failure to degrade glycosaminoglycans
mucopolysaccharidosis
25
where and how are glycoproteins degraded in the cell
lysosomes with hydrolases
26
what chemical property of glycosaminoglycans allows them to form lubricants and gels
hydrophilic, strongly - charge due to sulfates and carboxyl groups, attract water
27
where are mucins found
GI, resp, genitourinary tracts
28
synthesis of N linked glycoproteins
occurs in ER co translationally
| added as a block of sugars
29
synthesis of O linked glycoproteins
in Golgi post translationally
| added one at a time
30
what class of enzyme is responsible for adding sugars to O linked glycoproteins
glycosyltransferases
31
what is the structural difference between a glycoprotein and a proteoglycan?
glycoprotein--no serial repeat, mostly protein
| proteoglycan--serial repeat, mostly sugar
32
oligosaccharide
3-15 sugars covalently bound in linear or branched chain (eg ABO blood group antigens)
33
polysaccharide
long linear or branched polymer of sugars (eg glycosaminoglycans, glycogen, starch)
34
glycosidase
cleaves glycosidic bond (b/w two monosaccharides)
35
glycosyltransferases
form glycosidic bonds
36
oligosaccharyltransferase
transfers a pre-formed oligosaccharide from its lipid anchor to an appropriate Asn residue in a polypeptide during N linked glycosylation in the ER
37
linear polymer of a repeating disaccharide unit with many negative charges on carboxyl and sulfate groups, form gels
glycosaminoglycan
38
Inclusion cell disease
defect adding M6P tag on lysosomal hydrolases
39
digestion of obsolete cell parts
autophagy
40
return to a different plasma membrane domain in a polarized cell
transcytosis (antibody transfer via breastmilk)
41
uptake of cholesterol from blood to make new membranes
receptor mediated endocytosis
42
defective LDL receptors so cholesterol uptake is blocked and builds up in blood, leads to heart attack
familial hypercholesterolemia
43
_____ exocytosis pathway: all proteins passing through the Golgi will enter this pathway unless directed elsewhere by a specific signal, vesicles bud from trans Golgi and fuse with plasma membrane, operates continuously
default
44
_____ exocytosis pathway: specialized secretory cells, use secretory vesicles, only in response to an EC signal
regulated
45
most cells have a thick layer of carbohydrate on their cell surface known as:
glycocalyx
46
enzyme that removes the carb from the protein
endoglycosidase
47
where O linked sugars are built
Golgi
48
trans Golgi sorts into these three destinations:
lysosome, plasma membrane, secretory vesicle
49
where N linked oligosaccharides are modified
Golgi
50
entry face of ER
cis
51
exit face of Golgi
trans
52
determinant of cell shape
cytoskeleton
53
organelle contiguous with nuclear envelope
ER
54
cell's permeability barrier
plasma membrane
55
component of thin filaments
actin
56
ribosomal RNA synthesis site
nucleolus
57
protein degradation signal
ubiquitin
58
toxin clean up site
peroxisome
59
protein synthesis machines
ribosome
60
chromosome home
nucleus
61
mtDNA shape
circular
62
microtubule organizing center
centrosome
63
process that produces most of a cell's ATP
ox phos
64
worn out organelles are digested here
lysosome
65
proteins synthesized in ER are modified in
Golgi
66
ATP generating powerplants
mitochondria
67
structures that form poles of the mitotic spindle
centrioles
68
double membrane protecting the genome
nuclear envelope
69
cell interior minus nucleus
cytoplasm
70
sorting station for endocytosed material
endosome
71
cytoskeletal element that arranges organelles
microtubules
72
extensively folded mitochodrial membrane forms
cristae
73
sea in which organelles reside
cytosol
74
lysosomal enzymes work best at __ pH
low
75
small organelles containing enzymes involved in oxidative reactions that break down lipids and destroy toxic molecules
peroxisomes
76
responsible for the transcription and processing of rRNAs and for assembly of ribosomal subunits
nucleolus
77
cylindrical protein degradation machines located in the cytoplasm
proteasomes
78
subunit for microtubule assembly
tubulin dimer
79
nucleotide bound to subunit of microtubule
GTP
80
cytoskeletal element most important for changes in cell shape
actin based microfilaments
81
filaments that provide strength to axons in the nervous system
neurofilaments
82
neurofilaments are a special type of
intermediate filament
83
centrosomes are assembly sites for
microtubules
84
kinesins move toward the __ ends of microtubules
+
85
dyneins carry ___ in a cilium
doublet microtubules are both track and cargo in cilium (so they can bend)
86
why is ciliary assembly essential for vision
rod and cone
87
cytoskeletal element with no structural polarity, not used as motility tracks, high tensile strength
intermediate filaments
88
specific enzyme defect produces a metabolic block, accumulation of substrate, deficiency of product
inborn error of metabolism
89
three distinct phenotypes from mutations of a single gene
phenotypic heterogeneity
90
mutations in different genes lead to same clinical phenotype
locus heterogeneity
91
stage in mitosis when chromosomes separate
anaphase
92
stage when chromosomes are best visualized
metaphase
93
nondisjunction during meiosis I results in daughter cells that are:
2-heterodisomic for A1 and A2
| 2-nullosomic for A1 and A2
94
nondisjunction in meiosis II results in daughter cells that are
2-normal
1-isodisomic A2 and A2
1-nullosomic for A
95
phase of recombination
prophase
96
stage of reductive division
anaphase I
97
meiosis of oocytes completed after
fertilization
98
primary oocyte arrested in ___ until ___
prophase I, ovulation
99
nucleotide
sugar, base, phosphate grp
100
nucleoside
sugar, base
101
bases with one ring
pyrimidines, CUT
102
bases with two rings
purines, AG
103
differentiation between A and G
G =O (big "GUst of AIR on my way to work")
| A does not have it
104
how to remember T
Tom does meth
105
how to remember C
Amy is a sight to see
106
number of base pairs per turn
10.5
107
angstroms per turn of B DNA
34A
108
base pairing: instead of anti conformations, bases are syn/anti, forms triple helix
hoogsteen
109
DNA is ___ stable at high pH
less
110
parts of chromosome responsible for accurate segregation of sister chromatids after chromosome replication, rich in ___ base pairs
centromeres, AT
111
telomeres are rich in ___ base pairs
GC
112
chromatin used for transcription
euchromatin
113
silenced chromatin
heterochromatin
114
enzyme that cuts strands to relieve topological stress
topoisomerase
115
attached to nuclear envelope, provides support and attached to chromatin
lamina
116
process that causes lamina disassembly during cell division
phosphorylation
117
Ran GAP is on the ___ side of the nucleus with higher concentrations of ___
cytoplasmic, GDP
118
Ran GEF is on the ___ side of the cell with higher concentrations of ___
nuclear, GTP
119
___ molecules are exported from the nucleus using Ran
RNA
120
___ molecules are transported into the nucleus using Ran
protein
121
4-8 aa's on a protein recognized by importin
nuclear localization signal
122
in the nucleolus, DNA in the ____ is not being transcribed
fibrillar center
123
in the nucleolus, rRNA molecules are being synthesized in this compartment
Dense Fibrillar Component
124
in this part of the nucleolus, there are maturing ribosome precursors
A Granular Component
125
rRNA precursor strand for ribosome synthesis
45 S
126
components of the small ribosomal subunit
18s rRNA
127
components of the large ribosomal subunit
5.8s, 28s, and 5s from elsewhere
128
test ribosomal translation before leaving nucleus
pioneering
129
mobile DNA elements
transposons
130
copies of true genes
pseudogenes
131
parts of DNA that code for product
exons
132
parts of DNA that are removed
introns
133
histone octomer contains ___
H2A, H2B, H3, H4
134
30nm fiber is held together by which histone
H1
135
use of N-terminal tail domains on histones
Histone code, post translational modifications (acetylation, methylation) which alter local chromatin structure and therefore gene expression
136
part of the nucleus composed of proteins, provides structure and organization, chromosomes in it have distinct territories
nuclear matrix
137
how chromosomes are attached to the matrix
MARs matrix associated regions
138
autoimmune disease, body makes antibodies to own nuclear antigens
sytemic lupus erythmatosus
139
cancer caused by mutation in nuclear PML protein
acute promyelocytic leukemia
140
mutation in SMN (survival of motor neurons) part of protein involved in RNA processing
spinal muscular atrophy
141
genes encoded on acrocentric chromosome stalk arms
for rRNA
142
capped telomere on acrocentric short arm
satellite
143
normal variation in chromosome banding
chromosome polymorphism
144
number of complete sets of chromosomes N, 2N, 3N
euploidy
145
gain or loss of chromosomes less than a complete complement
aneuploidy
146
how to get aneuploidy
meiotic OR mitotic nondisjunction in anaphase I
147
normal embryo with mitotic error that gives rise to some cells with three copies of chromosome, acquired
mosaicism
148
how to get testes, androgen
TDF/SRY
149
females have ___ of Müllerian ducts
proliferation
150
males have ____ of Wolffian ducts
proliferation
151
when does X inactivation occur
3-7 days into development
152
how many Barr bodies does a cell have
number of X chromosomes - 1
153
is x inactivation random or nonrandom
random (if non random due to structural abnormality, females could express X linked diseases)
154
how are X chromosomes inactivated
epigentically, with methylation
155
____ region of chromosome escapes X inactivation
psueoautosomal
156
phase when DNA replicates
interphase
157
Meselson-Stahl experiment showed that DNA replication is __
semi conservative
158
what stops DNA from replicating throughout cell cycle
cyclin dependent kinase
159
a mutation in MMR gene leads to this phenotype, causes this disease
mutator phenotype, non polyposis colon cancer
160
polymerases used in event of a DNA lesion to minimize damage
error prone DNA polymerase, by template switching or hopping over it
161
defect in replication stress response can lead to these two diseases
AT, Bloom Syndrome
162
how does AZT work
chain terminator, nucleoside analog
163
how does camptothecin work
targets Topoisomerase I
164
environmental DNA damaging agents
mutagens
165
how to repair template independent damage
direct reversal by photolyase
166
how to repair single strand DNA damage
BER, MMR, NER
167
how humans repair double strand breaks
non homologous end joining
168
disease caused by defective NER
xeroderma pigmentosum
169
head group of membrane lipids contains
OH group
170
longer and more saturated chains are ___ fluid (more/less)
less
171
cis double bond causes kinks, resulting in ___ fluid membrane (more/less)
more
172
characteristics of cholesterol
lots of rings, only hyrophilic structure is the OH group on the end
173
sphingosine backbone with a sugar attached to primary OH group
glycolipid
174
hydrophilic part of sphingomyelin
phosphoryl choline
175
primary force driving formation of lipid bilayers
hydrophobic effect
176
effect of cholesterol on membrane fluidity
overall, decreases, but increases fluidity at border of cholesterols bc chains can't organize
177
lipid bilayer is most impermeable to ____
ions
178
four ways drugs can enter cells
passive diffusion, hijack transporters, liposome delivery, protein transduction
179
how to remove integral membrane protein
harsh detergent
180
lipid rafts are involved in _____
signal transduction, protein sorting and recognition, viral entry or exit from cell
181
actin monomer binds _ and _
Mg and ATP
182
____ form by self assembly of actin monomers
microfilaments
183
adding units bound to ATP at one end, losing units bound to ADP at other end of microfilament
treadmilling
184
combination of plasma membrane and underlying mesh of crosslinked actin filaments
cell cortex
185
parallel, unbranched microfilaments
filopodia
186
branched, extensions of cell membrane, ARP mediated, involved in migrating cell
lamellipodia
187
contractile ring of microfilaments found in a ____ cell
dividing
188
type of myosin that doesn't form filaments. Monomeric, stand alone vesicle vector. Tails associate with membranes.
Myosin I
189
type of myosin that assembles into bipolar filaments, heads face opposite directions, doesn't move
Myosin II
190
what activates myosin
phosphorylation of associated proteins (caused by change in Ca concentration)
191
myosin regulation is known as ____
thick filament based regulation
192
regulation of muscle contraction is known as
thin filament (or actin) based regulation, faster
193
troponin's role
positions tropomyosin on actin filament. binds to Ca, tropomyosin, and actin
194
role of tropomyosin
covers (or uncovers, in presence of Ca) myosin binding site on actin
195
how Ca is released into muscle cell
AP to transverse tubules to SR to voltage gated channels, releases Ca
196
myosin pulls toward the __ end of the actin
+
197
how is the sarcomere array anchored to the plasma membrane
dystrophin
198
the ____ is divided into sarcomeres
myofibril
199
how are myofibrils connected to each other
desmin intermediate filaments
200
how is myosin held in place in the sarcomere
titin
201
what separates myofibrils
SR
202
myosin during rigor state
bound to actin, NO ATP
203
myosin during release
ATP BOUND, myosin head lowers affinity for actin
204
myosin when cocked
ATP hydrolysis causes translocation of myosin head, weak affinity for actin
205
myosin during Force Generating step of muscle contraction
phosphate dissociates, increased affinity of myosin for actin, activates power stroke
206
myosin during attached phase of muscle contraction
ADP dissociates as myosin head returns to original position
207
47, XXX
female, often undected, fully fertile, generally have chromosomally normal children
208
47, XYY
male, often undetected, normal, due to a nondisjunction error in the father
209
47, XXY
Klinefelter syndrome. Male with some female characteristics bc of week of development before X was inactivated. post pupertal hypogonadism, infertility
210
45, X
Turner syndrome. female, short stature, webbed neck in utero, usually infertile. 10% are mosaics, ratio of normal to abnormal determines severity (and a 46XY/45X can be either male or female. fine for males, detrimental for females)
211
XY female
androgen insensitivity, mutation of androgen receptor gene on long arm of X chromosome, +TDF/SRY, infertile
212
XX "Male"
can be treated, due to biochemical imbalance, virilization of female fetus that has congenital adrenal hyperplasia, lack of enzyme that allows androgens to build up in the body, male appearing infant
213
XX male is due to
an error in recombination during male meiosis. Balanced translocation with no clinical significance unless father passes X chromosome onto child
214
terminal deletion, Greek Warrior's helmet facial expession
Wolf Hirschhorn Syndrome
215
parents are normal but child has a deletion
de novo interstitial deletion
216
a duplication of the critical region of chromosome 21 can result in
Down Syndrome
217
reciprocal translocation risk
for chromosomally abnormal children
218
balanced translocation carrier with no risk to children
alternate segregation
219
balanced translocation carrier with risk to children
adjacent 1 segregation, adjacent 2 segregation, 3:1 segregation
220
translocation variant of standard reciprocal translocation, occurs only between two acrocentric chromosomes, only 45 total chromosomes but full content of DNA. Increased risk of ____
Robertsonian, nondisjunction
221
inversion when breaks occur on opposite sides of the centromere
pericentric
222
inversion on same side of centromere
paracentric, usually benign
223
An alteration in the DNA which has a population frequency less than 1%
rare genetic variant
224
Tay Sachs method of inheritance
autosomal recessive
225
presence in males of a single allele at X linked loci is:
hemizygosity
226
associated with rare autosomal recessive disorders
consanguinity in the parents of a proband
227
a mosaic individual has two or more cell lines of different genotypes derived from a ___ zygote
a single zygote
228
all or none expression a genetic disease genotype
penetrance
229
the occurrence together in a population of two or more alleles, each at a frequency greater than 1%, so that the heterozygote frequency is at least 2%
polymorphism
230
MOI hemophilia A
XLR
231
MOI CF
AR
232
MOI a-1 Antitrypsin def
AR
233
MOI DMD
XLR
234
MOI Tay Sachs
AR
235
MOI sickle cell
AR
236
MOI a and B Thalassemia
AR
237
MOI HD
AD
238
MOI DM
AD
239
DM disease stands for
diabetes mellitus
240
the proportion of the phenotypic variance caused by additive genetic variance
heritability
241
traits that are influenced by environmental factors, the recurrence risk is higher the more family members that are affected, gene-environment interactions, the more severe the malformation the greater the risk
multifactorially determined traits
242
when an allele/mutation is at a frequency of 1% or greater (2% or more of individuals will carry at least one autosomal copy)
polymorphism
243
genes/loci close together on the same segment of chromosome are said to form____ which tend to travel together through meiosis
haplotypes
244
distance between genes measured in centiMorgans
recombination distance
245
one centiMorgan represents approximately ______ base pairs
1 million
246
one centiMorgan represents a __% chance of crossover
1%
247
term used to describe co-segregation as two loci tend to travel together through meiosis
Linkage Disequilibrium
248
in linkage studies, neutral/benign mutations _____ a gene (what kind of marker) are better than those _____ a gene
within (intragenic marker); flanking
249
a sibling of a known carrier with no affected siblings has a __ chance of being a carrier of an autosomal recessive mutation
half
250
mother of an affected son that follows Haldane's Rule has a __ chance of being a carrier
2/3
251
phase is known when:
alleles at two loci are known to occur on the same homologous chromosome, alleles at two loci are known to occur on the opposite homologous chromosome, you can tell which haplotype came from which parent, haplotypes can be constructed
252
estimating the distance between the disease and the marker
If the recombination distance between the marker and the disease is 15cM, what is the real physical distance between the marker and the disease
the further apart, the more a two point recombination rate will underestimate the physical distance because of the increasing influence of double crossovers.
about 20 Megabase
253
if two loci are within 50cM of each other, they must/may not be on the same chromosome
must be on the same chromosome
254
three classes of mutations
linked extragenic markers, intragenic markers, disease causing-mutations
255
_____ binding of a ligand (signaling molecule) to a receptor protein on a cell induces a conformational change in the receptor, triggering changes in other molecules inside the cell
non covalent
256
receptor conformational change results in a change in ___ if the receptor is an enzyme, or a change in ____ for another molecule if the receptor lacks enzymatic activity
activity, affinity
257
molecules inside the cell that carry the signal away from the receptor
second messengers
258
the concentration of a signaling molecule depends on the rate at which new molecules ___ and the rate at which they are ____
appear, removed
259
rapid changes in signal strength require a (short/long) signal half life
short
260
cell responses to a particular signal depend on
signal molecule [ ]
number of available receptors
receptor affinity for signaling molecule
expression of tissue or cell type specific second messenger systems
261
long term changes in signaling molecule concentration often cause target cell ____
adaptation
262
ways to accomplish target cell adaptation
change number of available receptors, affinity of receptor for its ligand, response sensitivity of second messenger pathways to receptor activation
263
fewer receptors = (more/less) sensitive cell
less
264
the same type of receptor (can/does not) activate different second messengers in different cells
can
265
two signal molecules (may/may not) act through the same second messenger
may--a boost in the concentration of one signal makes the cell more sensitive to the other one
266
types of signaling that occur over short distances
autocrine, paracrine, synaptic
267
signals carried through bloodstream
endocrine
268
signals that originate outside the organism
sensory
269
endocrine signals in (low/high) concentrations with (low/high) affinity receptors
low concentration, high affinity receptors
270
neurotransmitters have (low/high) concentrations with (low/high) affinity receptors
high concentrations, low affinity
271
examples of small rapidly diffusing signal molecules with short half lives
NO, CO
272
what signal molecule regulates smooth muscle contraction
NO
273
how are hydrophobic molecules like steroids, retinoids, and thyroid hormones carried throughout the blood
binding proteins
274
eicosinoids
hydrophobic molecules that bind surface receptors, derived from phospholipids and include prostaglandins
short half lives, autocrine signals
275
action of anti inflammatories like cortisone and aspirin
inhibit synthesis of eicosinoids
276
examples of sensory signals
light, sound, chemicals (smells and tastes)
277
nuclear receptors are used for what kind of signals and what do they do
used for hormone binding
| activate gene transcription
278
example of a carrier protein for hydrophobic signal molecules like steroid hormones
albumin
279
how are nuclear receptors activated
binding of ligand to receptor causes inhibitory complex to dissociate, thereby activating receptor and exposing its DNA binding site
280
nuclear _____ induced by hormone binding is a mechanism common to many nuclear receptor family members
translocation
281
genes activated by the hormone occupied receptor
primary response gene
282
amplification as a result of nuclear receptors happens at the level of (transcription/translation)
transcription
283
how do hydrophilic signals work? four main types
ligand-gated ion channels, enzyme-linked receptors, catalytic receptors, trimeric G-protein linked receptors
284
different types of ion channels (four)
voltage gated, mechanically gated, gated by extracellular ligands (primary signals), or intracellular ligands (secondary messengers)
285
the most common enzyme-linked receptors are those that stimulate membrane-associated:
tyrosine--specific protein kinases (such as the src kinase)
286
when a neurotransmitter binds to a receptor on the post synaptic cell, what change occurs in the post synaptic cell
change in membrane potential
287
signals that travel within a tissue
paracrine
288
when sensitivity of a cell to ligands is decreased after prolonged exposure
adaptation
289
eicosinoids bind (surface receptors/intracellular receptors)
surface receptors
290
role of heterodimer formation in steroid hormone signaling
heterodimeric transcription factors formed by nuclear receptors allow different cell types to respond differently to the same steroid hormone
each cell type can express a different partner to make a different heterodimer
291
phosphates may be added to the hyroxyl groups of which aa's
serine, threonine, tyrosine
292
what does phosphorylation change on/for a protein
activity, conformation, new interaction site
293
how do you turn off a protein that is activated by phosphorylation
phosphatase
294
some G proteins hydrolyze GTP so slowly that they effectively remain "on" unless activated by a __
GAP
295
reactivation of the G protein requires the release of GDP and binding of GTP, which usually requires a ___
GEF
296
two classes of G proteins
trimeric, monomeric
297
signal-on state of a G protein
GTP bound
298
subunits of a trimeric G protein
alpha, beta, gamma
299
trimeric G protein subunit with the guanine nucleotide binding sites
alpha
300
the a/b/g-GDP trimer is (active/inactive)
inactive
301
trimeric G proteins are linked to the (cytosolic/extracellular) side of the plasma membrane by lipid tails
cytosolic
302
when the ligand binding site of a GPCR is occupied, a trimeric G protein can bind to the intracellular part of the receptor, which stimulates ______
GDP-GTP exchange
303
the GPCR (does/does not) bind directly to GTP
does not
304
after the a and b/g subunits of the trimeric G protein separate, they bind to and alter the activities of:
membrane associated enzymes or ion channels
305
events triggered by G protein activation depend mostly on which gene family the __ subunit comes from
alpha
306
the bound GTP is (slowly/quickly) hydrolyzed and the inorganic phosphate is released (slowly/quickly)
slowly, quickly
307
GDP dissociates (slowly/quickly) from the alpha chain of the alpha subunit in a trimeric G protein
slowly
308
activation of Gs family members stimulates ___ raising ___ concentrations
adenylate cyclase, cAMP
309
increased cAMP concentrations stimulate ___
PKA
310
PKA is a _______ kinase
serine/threonine
311
binding of alpha-s to adenylate cyclase also stimulates alpha-s ___ activity, shutting off the signal
GTPase
312
PKA structure: _ catalytic subunits and _ regulatory subunits
2, 2
313
if no cAMP is present, PKA catalytic subunits are _____ by the regulatory subunits
inhibited
314
cAMP interacts with which subunits of the PKA, and causes them to do what
regulatory, dissociate
315
how are cAMP levels lowered
phophodiesterase
316
what does GTP hydrolysis achieve for the Gs family of G proteins
lowers cAMP
317
activation of __ family members inhibits adenylate cyclase, reversing the effects of Gs (and alters K+ channel conductance in some cells)
Gi
318
activation of Gq family of trimeric G proteins does what?
stimulates phospholipase CB, which degrades membrane phospholipids
319
IP3 is made when phospholipase C cleaves phosphoinositol bisphosphate when Gq is activated. IP3 does what?
opens gated Ca++ channels in the ER
320
when IP3 releases Ca++ from the ER, what are stimulated?
CAM kinases
321
CAM kinases use ___, a small Ca++ binding protein, as a regulatory subunit
calmodulin
322
resting intracellular Ca++ concentrations are (low/high)
very low
323
activation of the Gq linked GPCR leads to activation of a myosin light chain kinase, a CAM kinase that _____ smooth muscle and non muscle myosin light chains, activating contraction
phosphorylates
324
DAG activates ___ by increasing its affinity for Ca++, which is required for ___ (same) activation
PKC
325
______ are tumor promoters--they irreversibly bind to and activate PKC, permanently stimulating a pathway involved in regulating cell division
phorbol esters
326
basic mechanism of receptor kinase activation
receptor dimerization causes autophosphorylation of tyrosine residues in the receptor itself and stimulates kinase activity
327
transphosphorylation
two subunits each act on each other--why dimerization is needed in tyrosine kinases
328
___ domains on cytoplasmic proteins bind to phosphotyrosine groups on the receptor
SH2
329
role of the ligand in tyrosine kinase activation
brings the domains together to form a dimer
330
how is the signal relayed by a tyrosine kinase?
intracellular signaling proteins bound to phosphorylated tyrosines carry the signal into the cell's interior
331
examples of second messenger pathways of receptor tyrosine kinases
phospholipase C binds by its SH2 domain and stimulates IP3 and PKC pathway (same as Gq)
adaptor proteins indirectly activate monomeric G proteins of the ras family (GEF/GAP)
activated ras stimulates a MAP (mitogen activated protein kinase) cascade
332
MAP cascade
MAP kinases are mostly serine/threonine kinases with specificity for targets important in growth control including transcription factors that regulate cyclin genes, cyclin dependent kinase inhibitors
333
there is a (small/wide) range of tyrosine kinase diversity
wide range of diversity
334
tyrosine kinase receptors have been identified as the products of genes that are mutated in human ___
tumors
335
tyrosine kinase *linked* receptors
lacks kinase activity but dimerization stimulated by the ligand activates a separate protein tyrosine kinase associated with the receptor protein
336
example of tyrosine kinase linked receptors
JAK-STAT pathway
337
stimulation of __ activates a phospholipase, which cleaves PIP2 into IP3 and DAG. IP3 binds to ligand-gated ___ channels in the ER and releases __ (same) into the cytosol
Gq, Ca++
338
What are SH2 domains and what role do they play in signal transduction
SH2 domains bind to aa's that include phosphorylated tyrosine residues. Through binding, they change the conformation of the SH2 domain protein and signal to the rest of the cell that a receptor tyrosine kinase has been activated.
339
how is PKA activated
cAMP through Gs
340
how is PKC activated
by DAG through Gq
341
how is CAM kinase activated
by calcium, through Gq or other signaling pathways that increase calcium concentrations
342
the phosphorylation of one receptor molecule by another after dimerization of the receptor which passes the signal from the EC domain to the cytoplasmic domain of the receptor
transphosphorylation
343
steps of GPCR's that allows a signal to diffuse throughout the cell
cAMP and calcium
344
why have tyrosine kinase genes been identified as proto-oncogenes
they are involved in signaling pathways that regulate passage through the cell cycle. continuous activation can lead to uncontrolled cell division
345
which type of GPCR usually as the higher rate of spontaneous GTPase activity (monomeric or trimeric G proteins)
trimeric G proteins can self inactivate through GTP hydrolysis while monomeric G proteins generally require the activity of a GAP in order to shut off the signal
346
what are connective tissues primarily composed of
extracellular matrix
347
three parts of adhering (anchoring) junctions
transmembrane glycoprotein-interacts with proteins on adjacent cells or with proteins of the ECM
complex of proteins on the cytoplasmic face of the junction forming a plaque that mediates the association between the membrane protein and the cytoskeleton
cytoskeleton network-either actin or intermediate filaments
348
function of adhering (anchoring) junctions
maintain integrity of the tissue when subjected to mechanical stress (skin, muscles)
349
what would happen if adhering (anchoring) junctions didn't have attachment to a cytoskeleton network
the cellular tissues would be unstable since the glycoproteins could not be pulled out of the lipid based (fluid) membrane
350
two types of microfilament based adhering/anchoring junctions
adherens (adhesion belts), focal adhesions/focal contacts
351
adherens junctions (adhesion belts) are a type of __-__ junction
cell-cell
352
what are the major transmembrane protein component of adherens junctions (adhesion belts)
cadherins
353
cadherins associate with identical cadherin molecules on neighboring cells via ___ interactions
homophilic
354
plaque proteins stabilize the link to the ___ cytoskeleton (adherens junctions/adhesion belts)
actin
355
in addition to providing strength, the positioning of adherens junctions towards the apical surface of cells allows for oriented contractions of the actin filaments to initiate an _____ of the ____ ___
invagination of the epithelial sheet, which can then pinch off to form a separate tube of epithelial cells
356
how is the neural tube formed during embryogenesis
invagination of epithelial cells to form a tube using actin filaments and same-oriented epithelial cells (adherens junctions)
357
epithelial sheets express _ cadherin while neural tube cells express _ cadherin
E, N
358
focal adhesions/focal contacts are a type of ___-___ anchoring junction
cell-matrix
359
transmembrane glycoproteins found in focal adhesions
integrins
360
focal adhesions are a type of (hetero/homo) philic type junction
heterophilic junction
361
____ adhesions are important in dynamic events such as cell motility in the context of cancer cell migration and metastasis
focal
362
focal adhesions require (extracellular/intracellular) Ca++
extracellular
363
adherens junctions (adhesion belts) require (extracellular/intracellular) Ca++
extracellular
364
cell-cell anchoring junction, cadherins are the major membrane component, homophilic interaction between cells, plaque proteins link cadherins to the intermediate filament cytoskeleton
desmosomes
365
cell-matrix anchoring junction with integrin as the major transmembrane glycoprotein component, link epithelial cells to underlying basal lamina in a heterophilic interaction
hemi-desmosomes
366
integrins associate in a (homo/hetero) philic way with ECM
hetero
367
basal lamina is a special type of
ECM
368
desmosomal disorders (two)
pemphigus: autoimmune to skin desmosomal cadherin causing destabilization of cell-cell interactions
empidermolysis bulosa simplex: defect in intermediate filament assembly causing loss of integrity of desmosomes and hemi desmosomes
369
functions of tight junctions
block paracellular transport (across sheets of epithelia) and promote transcellular transport (from gut to blood stream through epithelial cell)
370
tight junctions partition membrane proteins into correct regions of the cell membrane and thereby maintain cell ____
polarity
371
proteins composing the tight junctions (two)
claudin and occludin-homophilic interaction
372
tight junctions (do/do not) rely on the cytoskeleton for integrity
do not rely on it
373
gap junction function
communication between neighboring cells in electrically excitable cells (cardiac muscle)
374
protein component of gap junctions
connexin (six of them form a connexon)
375
small molecules can pass through gap junctions. this is important for setting up ____ gradients within epithelial sheets which can provide ___ information during embryogenesis
concentration, positional
376
gap junctions type of association homo philic/phobic
homophilic
377
gap junction regulation: high Ca++, low pH
gap junction is closed
378
gap junction regulation: low Ca++, high pH
Gap junction is open
379
____ cells generate the ECM in many connective tissues
fibroblasts
380
____ cells generate the ECM that forms cartilage
chondroblasts
381
____ cells generate the ECM that forms bone
osteoblasts
382
three major structural components of the ECM that contribute to the phenotype of connective tissues
fibrous proteins, bulky fillers, cross linker proteins
383
three types of fibrous proteins in connective tissues
fibrillar collagen (tensile strength), non fibrillar collagen (basal lamina, cannot form higher order fibrillar structures), elastin (allows stretching)
384
fibrillar collagen characteristics
post translational modifcations, pro collagen triple helix, secreted collagenases cleave off propeptides, form higher order structures
385
genetic disease associated with dysfunction in collagen synthesis/assembly, hyper extensible skin
Ehlers Danlos Syndrome
386
mutations in fibrillin gene are the cause of ____ syndrome, a condition that results in weak artery walls (severe cases-rupturing of the aorta)
Marfans Syndrome
387
characteristics of bulky fibers
complex proteoglycan molecule--protein backbone with serine residues, sugar side chains undergo carboxylation and sulfation so they have a (-) charge which attracts H2O and makes a gel
388
primary function of bulky fibers
to fill space and permit the movement of water soluble molecules and cells
389
cross linker proteins (fibroconectin and laminin) functions
link cellular tissue layers to connective tissue layers
390
fibroconectin is a dimer held together by disulfide bonds. It has binding sites for:
heparin, cell surface receptors (integrins), collagen (not type IV), fibrin, syndecan (focal adhesions)
391
lamin binds to __________ unlike fibroconectin
type IV collagen
392
two types of junctions that do not utilize interactions with the cytoskeleton
gap junctions and tight junctions
393
basal lamina is used for what function
molecular filter in the kidney
394
the basal lamina acts as a permeability barrier in the glomerulus, allowing the passage of ___ and blocking the loss of ____
small metabolites, blood proteins
395
a condition that results from environmental insult that mimics a Mendelian disease
phenocopies
396
mother is affected and so are all her children, of all genders
mitochondrial
397
Haldane's rule applies when
X linked recessive, reduced fitness, no other family history (goes by the mother's side)
398
X linked recessive affects
boys when mother is affected, girls when father is affected
399
pedigree showing evidence of germ line mosaicism in parent
unaffected male with two affected children by two different partners
400
SNP pros and cons versus microsatellites
SNPs are less informative but more stable than microsatellites
401
DMD seen in child but no deletion found in mother's blood. fetus could still have a ___% chance of having it because the mutation could be in her ______
7%, germline
402
G1 cyclins are synthesized in G1 as regulatory subunits of ___
CDKs
403
non dividing cells usually stop in which phase of the cell cycle
G1
404
MAP kinase activity in G1 increases synthesis of ____ and blocks the action of __ and related inhibitor ___
cyclin subunits, p21 and p27
405
what proteins are synthesized during S phase of the cell cycle
histones
406
what duplicates in S phase but doesn't separate until the start of mitosis
centrioles
407
what event in G2 phase blocks further transcription for the cell
chromosome condensation
408
what is the role of cohesins in the cell cycle, and when are they added
they are added during G2 and at the start of M
| they help package chromosomes for mitosis by linking the replicated sister chromatids together until anaphase
409
the onset of mitosis is controlled by what enzyme's activity
kinase
410
what motor protein crosslinks the microtubules during mitosis
kinesins
411
what is located at the primary constriction point of each duplicated chromosome during metaphase
kinetochores
412
unattached microtubules during metaphase are called ___ microtubules
astral
413
the trigger for the metaphase to anaphase transition is the tension on all kinetochores, which inhibits the activity of a _____ (enzyme)
kinase
414
when all kinetochores are under the same tension during metaphase, the _ _ _ becomes active and triggers separation of chromatids
Anaphase Promoting Complex APC
415
during telophase, the division of the cytoplasm begins with the assembly of a ___ ___
contractile ring
416
failure of cytokinesis after mitosis results in:
binucleated or multinucleated cell
417
most animal cells blocked in mitosis for prolonged periods undergo ____
apoptosis
418
checkpoints during the cell cycle
entry into mitosis (G2/M)
entry into S
exit from mitosis
419
a serine/threonine specific protein kinase that has no activity unless combined with a matching regulatory subunit
cyclin dependent kinase
420
inhibition of cdk's
inhibitory phosphates
421
activation of mitotic cdk
add phosphates to two different places of the kinase subunit by two different kinases
422
inactivation of cdk
1. cyclin subunit is ubiquitylated by an E3 ubiquitin ligase, targeting the cyclin subunit for proteolytic destruction by the proteosome
2. the activating phosphate is removed from the kinase subunit
423
what is the role of the Anaphase Promoting Complex (2 roles)
ubiquitin ligase that turns off cyclin dependent kinases
| promotes chromosome separation by activating the protease Separase
424
role of p53 in the cell cycle
stabilizes the protein against proteolytic degradation and activates it, inhibits cdks by increasing the concentration of proteins that bind to cdks and block their activity
425
new deoxynucleosides are only incorporated into DNA during the __ phase of the cell cycle
S
426
three major checkpoints in cell cycle
entry to M, G1/S border, metaphase to anaphase
427
what prevents DNA from being replicated more than once every cell cycle
origins of replications
428
what mitotic events occur before the nuclear envelope breaks down
chromosome replication, spindle elongation
429
the event that triggers cells to pass the metaphase/anaphase checkpoint and proceed through to the final steps of mitosis is:
tension on all kinetochores from bipolar microtubule movement
430
during the progression through the cell cycle, the molecule whose concentration/amount is most carefully controlled is:
nuclear genomic DNA
431
genetic defect in apoptosis
syndactyly
432
difference between cells undergoing apoptosis and necrosis
apoptosis: cells shrink then release small membrane bound apoptotic bodies that are phagocytosed by macrophages
necrosis: cells swell and burst, releasing their intracellular contents and frequently causing inflammation
433
when there is insufficient trophic factors and no phosphorylation of Bad, the cell:
undergoes apoptosis by cytochrome C which activates the caspase cascade
434
when there is sufficient trophic factor, Bad is phosphorylated and the cell:
can survive
435
causes of senescence
normal adult cells that have reached the end of their telomeres (telomerase not active)
436
protein important for blocking entry into S phase following DNA damage or when chromosomes have lost their telomeres
p53
437
growth factor that acts locally
platelet derived growth factor, present in blood serum
438
growth factor that acts systemically
erythropoietin
439
mechanism used by stratified epithelia to regulate cell proliferation
anchorage dependent cell growth
440
how cells know when to stop dividing during wound repair
density dependent growth inhibition (when cells touch each other they stop dividing)
441
cancer cells usually lack (four things)
growth factor dependence
anchorage dependence
cell-cell contact inhibition
do not become senscent
442
genes that encode normal cell proteins that function to stimulate cell growth and division
proto oncogene
443
oncogenes are ___ active proto-oncogenes
constitutively
444
how many alleles of a proto oncogene need to be mutated to affect cell growth
one
445
how many alleles of a tumor suppressor gene must be mutated for the gene to be inactivated
two
446
an inhibitor of gene transcripition. In its active state, ___ binds and sequester the transcription factor E2F. It is controlled by a cdk
Rb, retinoblastoma
447
how is Rb inactivated
phosphorylation
448
if p53 is damaged or missing, what will happen to a cell with damaged DNA
it will continue to divide
449
how does HPV cause cancer
produces two proteins that bind to p53 and Rb so cell can undergo unregulated division
450
how does SV40 virus cause cancer
produces large T antigen that binds both Rb and p53, sequestering those proteins and preventing them from regulating cell division
451
the conversion of pro caspases to caspases leads to:
apoptosis
452
___ levels of trophic factors in the developing brain prevent apoptosis
high
453
the kinase that phosphorylates the Rb protein, allowing E2F dependent transcription, can be best described as
a proto oncogene
454
the proportion of phenotypic variance caused by additive genetic variance
heritability
455
antibiotic resistance due to mutation is (a response/a preexisting selection factor) to the antibiotic
preexisting selection factor
456
the prophage pathway of transduction can give way to the lytic pathway via
an induction event caused by stress (virus knows it needs to get out of a stressed host)
457
five ways transposons contribute to genetic diversity
disrupting genes in which they land
altering the expression of neighboring genes
facilitating rearrangement of the bacterial chromosome through homologous recombination between transposon copies
by hopping into plasmids or bacteriophages and transferring their genes via these vectors to other bacteria
amplifying copies of antibiotic resistance genes
458
a mechanism by which bacterial transposons move that results in amplification
transposon is copied by DNA replication and inserted into a new site
459
type of transposon movement that does not result in amplification
non replicative transposition
| cuts from its old site to move to a new site
460
number of possible gametes from each parent
2^n (n=23) due to independent assortment
461
genes involved in eukaryotic homologous recombination
RAD
462
how to retrotransposons move in humans
RNA intermediate
463
how do retrotransposons contribute to human genetic diversity (three ways)
disrupt gene function by insertion
affect expression of genes
create sites for illegitimate homologous recombination known as unequal crossovers
464
unequal crossovers created by retrotransposons create:
gene families (like the globin genes)
465
anchors cell membrane of muscle and stabilizes the cytoskeleton-plasma membrane interactions
dystrophin
466
deletion of the exons that code for the repeat of unequal crossovers leads to shorter forms of what protein in muscle
dystrophin, leads to muscular dystrophy
467
retrovirus genome
ssRNA
468
how were many of the known oncogenes discovered
they were tumor causing passengers on animal retroviruses
469
how is homologous recombination initiated
double strand DNA breaks
470
homologous recombination results in the (reciprocal/non reciprocal) exchange of genetic information between homologous chromosomes
reciprocal
471
the higher the Lod score the more likely the distance associated with it is ___
true
472
the smaller the theta associated with the maximum Lod, the (closer/further) the marker is to the disease gene
closer
473
knowing whether two alleles, at different loci, were inherited from the same parent
knowing phase
474
DMD is a large gene. What is the implication of that for intragenic markers?
Not as useful, still have to consider recombination
475
alleles at different loci are said to be in _____ when on the same chromosome (cis)
coupling
476
alleles at different loci are said to be in ____ when on opposite chromosomes (trans)
repulsion
