Exam 2, Foundations Flashcards
(143 cards)
1
Q
Type I collagen is found
A
in bone, skin, tendon, ligaments, cornea, and internal organs
2
Q
Type II collgen is found
A
Cartilage, IV discs, eye
3
Q
Type III collagen is found in
A
skin, blood vessels, reticular fibers
4
Q
Type IV collagen is found in the
A
basal lamina (sheetlike instead of fibrillar)
5
Q
Ehler’s Danlos Type IV
A
mutations in collagen Type III
6
Q
Marfan’s syndrome
A
mutations in the fibrillin gene
7
Q
hyaluronic acid is different in that it
A
not bound to protein and does not form a preoteoglycan
8
Q
Fibronectin
A
connects cells to the components of the ECM and collagen
9
Q
Laminin
A
binds to membranes of epithelial and muscle cells
10
Q
Mast Cells bind which type of receptors?
A
IgE receptors preent on the plasma membrane
11
Q
allergic rxns are mediated by
A
mast cells and IgE
12
Q
Alport’s syndrome:
A
Type IV defect
13
Q
what is the enzyme and cofactor involved in the committedstep of purine synthesis?
A
APRT and glutamine
14
Q
Lesh nyhan syndrome comes from a defect in
A
HGPRT
15
Q
defect in HGPRT causes? (how)
A
HGPRT decreases salvage pathway and leads to increased levels of uric acid through increased purine catabolism and gout. IT is also thought that HGPRTis important in the briain which is why it causes lesch nyhan
16
Q
orotic aciduria is due to
A
a defect in UMP synthase, the enzyme that converts orotic acid to OMP and OMP to UMP during pyrimidine synthesis.
17
Q
orotic aciduria is characterized by
A
macrocytic anemia and delayed physical an dintellectual development
18
Q
treat orotic aciduria using
A
UMP because UMP will then go on to make udp and utp and CTP, and will also inhibit the action of CPSII and CAD which are involved int ehf irst step of the pyrimidine synthesis
19
Q
Ribonucelotide reductase is used to convert
A
ribonucleic acid to deoxyribonucelic acid
20
Q
what stimulates and inhibits the activity of RNR
A
ATP stimulates and dATP inhibits
21
Q
ATP binding to specificity site
A
makes RNR bind UDP or CDP t make dCTP or dUTP which is rapidly converted to dTTP
22
Q
what stimulates the production of dGDP
A
dTTP
23
Q
What is the result of ADA (adenosine deaminase deficiency)
A
SCID
24
Q
Explain SKID
A
when ADA is broken, dAMP builds up. B and T cells rapidly phisphorylate this dAMP to dATP which negtively regulates ribonucelotide reductase. Now RNR is inhibited and you cannot make nucelotides and cell proliferation halts
25
hydroxyurea targets
ribonucleotide reductase by quenching the free radical on it and cell cannot divide
26
Fluorodeoxyuracil targets
thymidylate synthase by trapping the enzyme
27
methotrexate inhibits
Dihydrofolate reductase (DHFR) which allows the reduction cascade of thimydilate synthase, which is important in the production of dTTP from dUTP. PRevents the cycing of DHF back to THF to continue the production of dntps
28
why is dTTP rapidly made from dUTP
because high levels of Us are mutagenic
29
what is it important to measure before treating a patient with 5-fluorouracil and why?
It is importnt to measure dihydropyrimidine dehydrogenase activity because defects in this enzyme reduce pyrimidine catabolism and can lead to high circulating levels fo 5-fluorouracil
30
allopurinol blocks what and is used for what
xanthine oxidse which converts xanthine and hypoxanthine into uric acid. It decreases the aount of uric acid and also hypoxanthine can be used in salvage to make purine, and the production of these purines can inhibit APRT and decrease purine synthesis. It is used to treat gout.
31
genetic anticipation is worse when passed on from a
father
32
CAg codes for
glutamine
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stretches of glutamine promote
aggregation
34
the DNA pol I has three functions. The 3' -->5' exonuclease is used for
editing out incorrectly added nucelotides which is stimulated by mismatches
35
DNA pol I makes DNa in the
5' --> 3' direction
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the 5' --> 3' exonuclease activity og DNA pol I is used to
remove DNA or RNA primars. It binds to sinle strand nicks and excises DNA in front and behind it. Involved in nick translation.
37
What is MGMT and why do i care about it?
MGMT is methyl guanine methyl transferase. Alkylation of guanine leads to a loss of a base and problems in replication. When there is alot of this, p53 is active and the cell will die. Use temozolamide to alkylate guanine and lead to activaatioj of P53 and cell death. MGMT is responsbible for converting guanine that has been alkylated back to guanine and protecting the cell. If there is alot of MGMT that is active, the cell will be resistant to remozolomide. When MGMT is methylated, MGMT is inactive. So Test to see if MGMT is methylated/ inactive and if it is, then the patient will respond to temozolomide.
38
how does telomerase work?
telomerase adds repeat structures TTAGGG tot he 3' end of each strand. It creates a G rich non-coding send. When telomere level falls, cell division ceases.
39
homologous recombination is done through
BRCA1 and BRCA2
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nonhomologous end joining is good or bad?
BAD BAD BAD
41
Why are cancers with BRCA1 and BRCA2 mutations more sensitive to radiation?
radiation induced double stranded DNA breaks. BRCA1 and 2 are responsbiel for ds repair, so when there are mutations the cell is not repaired and undergoes cell death
42
what in the world is base excision repair and what disease does it relate to?
Base excision repair is used when a guinine is exposed to ROS and forms 8-oxoguanie. The 8 oxoguanine is removed a flap is created, and when it is rich in CAG repeats, the Cs and Gs are very stbale and pair together. They are resistant to cleavage by the flap endonucelase and the repeat can be expanded.
43
What does UV light do to DNA aand what kind of DNA repair does it incite?
UV light induces nucelotide excision repair where bulky pyrimidine dimers formed by UV light are repaired. UV light promites the formation of thymidine dimers
44
What happens in the nucelotide excision repair pathway?
cut the DNA on either side of the damage
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BAse-Hunter
Base excision repair = huntingotn
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problems with nucelotide excision repair result in
xeroderma pigmentosa
47
the signature of a translesion synthesis is a
CC --> TT change in bases
48
what is mismatch repair?
mismatch repair is the repair machinery working at replication forks -> cuased by polymerase making mistakes
49
problems in mismach repair lead to
lynch syndrome, a non-polpous colon cancer
50
BRCA1 and BRCA2 are genes that
produce tumor supressor proteins
51
myc is a
proto oncogene
52
Rb is a
tumor supressor that when phosphorylated by G1-CDK allows E2Fto stimulate the G1/S phase
53
tumor supressor have what type of mutations
loss of function
54
APC targets what for degredation?
M-phase cyclin and securin. which negatively regulates separase, which separates sister chromatids
55
what does wee 1 do?
wee1 puts a negative phosphorylation onto M-cdk and preventing the initiation of mitosis. When wee1 is gone, the cells enter mitosis too eaarly and are too small.
56
what does CDC25 do
CDC25 takes off the inhibitory phosphate added by wee1
57
what usually keeps P53 off?
MDM2, which ubiquitinates it
58
what does P53 do
It is a tumor supressor and a TF that induces the expression of p21 and other proteins that supress the cell cycle progression by inhibiting s-cdk
59
symptoms of CML
inability to progress along the erythroid and megakaryocyte lineage. with increased white cells.
60
whats up with BCR ABL
ABL codes for a tyrosine kinase in cell proliferation that has a catalytic and regulatory domain. When the translocation occurs between 9 and 22 the reguaotry domain is lost.
61
what do you use to treat CML
imatinib which binds to the tyrosine kinase activity and inhibiting it
62
test for CML using
fish or PCR
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major molecular response is
10000 fold reduction in bcr abl gene
64
what are acetyl groups added to and what is the effect
lysines. When this happens the positive charge is lost and the packing on the histone gets looser allowing for DNA --> transcription of DNA
65
what are transcripts capped by on the 5' end
7-methyl gunaine structure
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start codon is
AUG methionine
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stop codon
UAG, UGA , UAA
68
missense
when a single AA is changed thus changin the codon added
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frameshift
reading frame shift from addition or deletion
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nonesense
insertion of a stop codon
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silent
degenerate DNA code
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cytosine methylation is associated with
repression of gene expression due to steric hinderance and condensing chromatin
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promoter regions are rich in GC repeats called a CG island. when these are methylated
gene repression
74
general overview of notch signalling
another cell with delta on it interacts with notch, notch is cleaved and the intracellular part goes into the nucleus, displaces acetyltransferases on hstones and gene expression!
75
General WNT process
wnt is iportant in epidermal morphogenesis. B-catenin is usaully phosphorylated and thus ubiquiniated by APC. When wnt binds, APC falls off, b catenin goes to the nucelus as a TF -> proliferation
76
hedgehog signalling general process
when hedgehog is off, protein ci is degraded and the degraded parts go to the nucelus as a reprssor. When hedgehog is active, CI is not cleaved and gos to the nucleus as an activtor that recruits histone acetyl transferases
77
epimers
differ at a single carbon
78
alpha is when
C1 group is down and in trans
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beta is
c1 group is up or in cis
80
pattern of glucose
down up down up
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mannose is a
C2 epimer f glucose because the C2 carbon is up instead of down
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galactose is a
c4 epimer of glucose because the C4 carbon is up instead of down
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to distinguish D-glucuronic acid from l-iduronic acid
If C6 is up = D
| if C6 is down = L
84
default pathway in protein production
secretion
85
glycosyltation occurs
co-translationally
86
carbohydrates are linked through n-glycosidic bonds to proteins on
asparagine residues: ASN-X-SER
87
What holds an oligosacharride in place waiting for a signal recognition sequence for glycosylation to come through?
dolichol : it is attached to to phosphates and an oligosacharide and when the asn-x-ser (or thr) comes through it is tranfereed onto the protein
88
mislocation of lysosomal hydrolases results in i cell disease and is the result of a missing
mannose-6-phosphate. Cells are defective at targeting certain enzymes to lysosomes
89
what defines the complex class?
the prescence of sialic acid
90
what is the importance of glycosylation?
protection from degregation and molecular recognition
91
Why would a new born baby get jaundice as a result of blood type incompatibility
If a mother is O she will make antigens to A and B, but the baby will not make antigen to her. So, mom's serum is destroying the baby's blood --> jaundice
92
type B vs A where B has a ____ and A has a ____
A has a galnac o, B has a gal
93
general structure of a GAG
disacharride repeats made of a carbohydrate acid (glcNac or GalNac) and an amino sugar (GlcA). They are VERY negatively charged and do not have a compact folded shape
94
tell me about the flu
the flu virus has hemaglutanin which recognizes sialic acid in the respiratory tract. It will adhere and infect. Has an enzyme called neurominidase that cleaves off the sialic acid and allowed it to fall off and ifnect a new cell.
95
what does tamiflu do?
tamiflu looks like sialic acid, so binds to neuromididase and inhibits it. slows down the flu.
96
antibiotics are molecules that target
ribosomes of bacteria
97
hyaluronic acid is differnt becauase
it is not covalently attached to a protein and is the only GAG also found in bacteria. It is also unsulfated
98
Mucopolysachcharidoses are a result of
defects in degredation of GAGs since the undegraded or partially undegraded gags accumulate in lysosomes, they fall under the title of an LSD
99
Hurler disease is a defect in
alpha-irunidase , autosomal recessive
100
process of degredation of a mucopolysacharide
start from the non-reducing end, if there is a sulfur, remove with a sulfurtase, cleave off the iduronic acid
101
scheie and hurler scheie are when
you have a defect in alpha 1 iduronisdase (dermatan sulfate and iduronidase affected)
102
the repeat unit in collagen is
gly-x-y, where x is proline and y is hydroxyprline
103
the glycine in collagn is required because
of the small size: it allows the 3 chains to come into close contact
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the hydroxyproline/hydroxylysine is important in collagen because
they confer thermodynamic stability on the triple helix structure. proline --> stabalization and lysine --> crosslinking and glycosylation
105
type I collagen is found in
bone
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type III collagen is found in
blood vessels and skin
107
the enzymes that hydrxylate collagen on the pri and lys residues require what to function?
alpha ketoglutarate, o2, Fe, and VITAMIN C
108
scurvy is due to a
deficiency in vitamin C, so you dont have the hydroxylation on your collagen and you lose your thermo stability.
109
what are collagen pro pieces, when are they cleaved and why are they important
they are sequences found at the amino and carboxy termini and are necessary for triple helix formation and prevent the collagen from accumulating. They are cleaved off after they are secreted
110
Osteogenesis impoerfecta is a problem with
collagen type I, which is why it can be seen in the bone.
111
ehlers danlos is a problem with
collagen type III which is why is it seen in the skin and blood vessels. Ehler's danlos --> aortic dissection
112
type IV collagen has propieces, why are they important
the basal lamina that does not have its proieces cleaved after secretion. the propieces help to layer them into a network
113
wnt is said to be
autocrine / paracrine. aka acting in the same cell of a nearby cell
114
lynch syndrome
a defect in the APC of wnt signalling, (where wnt binds to the cell and causes b-catenin to be active and go to the nucelusleading to cell growth) lynch syndrome is a problem with the APC o beta catenin is always on.
115
big takeaway from hedgehod is that
cells have variable thresholds for response to the secreted shh signalling
116
how to know spleen or lymph node
lympph nodes have a sinus lumen that is not empty
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the thymus
has no germinal centers and is lobulated
118
macrphages are dervied from
blood monocytes
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mast cell derives from
immature mast cells
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prostaglandins are released from
mast cells
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mast cells are commonly located along
blood vessels
122
plasma cells differentiate from
lymphocytes
123
tensile strength refers to
collagen
124
intramembraneous ossification important in the
mandible
125
osteocytes are derived from
osteoblasts
126
vertebrae are an example of
endochondral ossification
127
periosteal bud formation in
endochondral
128
thymus stroma is made up of
epithelioreticular cells
129
humoral antibody response
B-lymphocytes
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hungtingtons disease is on chromosome
4: autosomal domnant
131
NF1
chromosome 17 autosomal dominant
132
Marfan
autosomal dominant fibillinopathy, chromosome 15
133
disease that is an example of locus heterogeneity?
TSC: tuberous sclerosis complex where autosomal dominant mutations on chromosomes 9 and 16 --> the same disease.
involves the CNS, eye, heart, kidney and lung
134
spinal muscular atrophy is autosomal recessive disorder
floppy infant
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type I osteoperosis
post emno pausal women, most severe
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type II osteoperosis
elderly due to osteoblastst aht dont work
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Type III osteoperosis
econdary to drug therapy
138
rickets due to
lack of vitamin D ad calcium int eh diet
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cathepsin K is a
lysosomal enzyme
140
Appositional growth:
growth occurs from outside borders; chondrocytes develop from the
perichondrium
141
Interstitial growth:
cartilage develops inside existing cartilage; happens from formation of isogenous groups
142
repair occursr through
endochondral ossicifation
143
PTH increases
CA in the blood
