FA 2015 Flashcards
(99 cards)
1
Q
describe de novo synthesis of pyrimidines
A
make temporary base - orotic acid
add sugar and phosphate
modify base
2
Q
whats used to make pyrimidines
A
carbamoyl phosphate + aspartate
3
Q
describe de novo synthesis of purines
A
start with sugar and phosphate
add base
4
Q
whats used to make purines
A
2x N10 formyl tetrahydroholate glycine glutamine aspartate CO2
5
Q
leflunomide
A
carbamoyl phosphate –> X inhibits dihydroorate dehydrogenase X –> orotic acid
6
Q
orotic aciduria
A
inhibits enzyme involved in conversion of orotic acid to UMP
7
Q
hydroxyurea
A
UDP –> X inhibits ribonucleotide reductase X –> dUMP
8
Q
5-flurouracil
A
dUMP –> X inhibits thymydilate synthase –> dTMP
decreased dTMP
9
Q
methotrexate
trimethoprim
pyrimethamine
A
humans
bacteria
protozoa
DHF –> X inhibits dihydrofolate reductase X –> THF
10
Q
6- MP
azithropurine
A
inhibites de novo purine synthesis
11
Q
mycophenylate
ribavirin
A
IMP –> X IMP dehydrogenase X –> GMP
12
Q
allopurinol
febuxostat
A
salvage purine pathway
hypoxanthine –> X inhibits xanthine oxidsase X –> xanthine –> X inhibits xanthine oxidase X –> uric acid
13
Q
probenecid
A
uric acid –> INHIBITS –> urine
14
Q
UGG
A
tryptophan - ony one codon = exception to degenerate/redundancy of the genetic code
15
Q
AUG
A
methionine - only one codon = exception to degenerate/redundancy of the genetic code
16
Q
describe DNA polymerase III
A
prokaryotic only
5’-3’ synthesis
3’-5’ exonuclease activity for proofreading
17
Q
describe DNA polymerase I
A
prokaryotic only
5’-3’ synthesis to replace RNA primer with DNA
3-5’ exonuclease
5’-3’ exonuclease to get rid of RNA primer
18
Q
Xeroderma pigmentosum - what goes wrong
A
defective ssDNA repair by UV light corrected by nucleotide excision (oligonucleotide removal, occurs in G1) – can’t fix pyrimidine dimers due to UV
19
Q
HNPCC - what goes wrong
A
defective ssDNA repair by mismatch - errors that occur in synthesis that are corrected in G2
20
Q
Ataxia telangiectasia and Fanconi Anaemia - what goes wrong
A
defective dsDNA repair by nonhomolougous end joining - correction of double stranded breaks (may lose genetic material, don’t need to be homologous)
21
Q
Xermoderma pigmentosum - clinical presentation
A
predisposition to squamous cell carcinoma + basal cell carcinoma + malignant melanoma at an early age due to inability to repair pyridine dimers produced by exposure to UV light (nucleotide excision)
AR
numerous hyperpigmented lesions and nodular and scaly growthrs on face
goljan page 206 for pic
22
Q
HNPCC - clinical presentation
A
increased risk of colorectal cancers without previous polyps; caused by germ line mutation in mismatch repair genes/G2 that cause a microsatellite repeat replication error/microsatellite instability – predispose to replication errors if there are mtuations in DNA repair enzymes/MMR genes – microsatellites become unstable (become longer or shorter) and produce RAMESHIFT mutatiosn that in activate or alter tumor suppressore gene function leading to cancer. MSI found in majority of HPMCC patients. :) try to not copy exact nedxt time becky :) its okay today bc you are a pukey face.
23
Q
Ataxia telangiectasia - clinical presentation
A
increased risk of developing malignant lymphomas
24
Q
Fanconi Anaemia - clinical presentation
A
can cause aplastic anaemia
don’t mess up with fanconi syndrome: polyuria, renal tubular acidosis type II, growth failure, electrolyte imbalances, hypophosphatemic rickets
25
what is fMet
AUG in bacteria - start codon
AND
stimulates neutrophil chemotaxis
26
list the stop codons pleease
journing of December till now
You go away UGA
You are away UAA
You are gone UAG
27
amantia phalloides!!!
inhibits RNA polymerase II - makes mRNA and can open NDA at promoter site
CXPX: four phases -- asymptomatic -- gi with diarrhoea and vomiting severe -- apparent recovery -- renal and liver failure in 7-10 days BCHM NOTES THROWBACK
28
rifampin
inhibits RNA polymerase in prokaryotes
29
Actinomycin D
inhibits RNA polymerase in prokaryotes and eukaryotes
30
whats the polyadenylation signal?
AAUAAA!!
31
sequence in the intron that splicesome makes a lariate out of
exon2 - OH - P - GU- A- AG - P - exon1
32
anti-spliceosomal snRNPs/antismith abs
```
highly sensitive (rule out bc TN high)
SLE
```
33
anti-U1 RNP abs
highly associated with MCTD - mixed connective tissue disease
34
Define and give examples of permanent cells
remain in G0 + regenerate from stem cells
| ex: neurons, skeletal muscle, cardiac muscle, red blood cells
35
Define and give examples of stable/quiescent cells
enter G1 from G0 when stimulated
| ex: hepatocytes and leukocytes
36
Define and give examples of labile cells
nover go to Go, divide rapidly with a short Gi, most susceptible to chemotherapy
ex: bone marrow, gut epilthelium, skin, hair follicle, germ cells
37
Role of the Golgi
distribution centre for proteins and lipids from the ER to vesicles/plasma membrane or lysosome
N-oligosaccaharides are modified at ASPARAGINE
O-oligosaccharides are added to LYSINE and SERINE
addition of mannose-6-phosphate sends to lysosome for destruction
38
I cell disease pathophys
N-acetylglucosaminyl-1-phosphotransferase --> failure to phosphorylate mannose residues on glycoproteins in the Golgi --> are secreted extracellulary instead of trafficked to vesicles,
39
I cell disease cxpx
```
coarse facial features
clouded corneas
restricted joint movement
high plasma level of lysosomal enzymes
often fatal in childhood
```
40
what causes proteins to accumulate in the cytosol that were produced in the RER (supposed to be secretory/vesicular proteins(
absent ro dysfunctional SRP/signal recognition particles - that shuttle the ribosome to the RER
41
who cares about the peroxisome?
metabolism of VLCFA, branched FA, amino acids
42
who cares about the proteasome?
degrades damaged or ubiquitin-tagged proteins
| defects associated with some cases of Parkinson dz
43
List drugs that affect microtubules
```
Mebendazole - anti helminth
Griseofulvin - anti fungal
Colchicine - anti gout
Vincristine/vinblastine - anti cancer
Paclitaxel - anti cancer
```
44
Karteneger Syndrome - clinical presentation
```
infertility in men and women
increased risk of ectopic pregnancy in women
bronchiectasis
recurrent sinusitis
situs inversus (dextrocardia on CXR)
```
45
what is oubain
inhibits the Na+K+ATPase by blocking the K binding site
46
what is digoxin and digitoxin
inhibit the Na+K+ATPase --> indirectly inhibits the Na+Ca++ exchange --> increased intracellular Ca++ --> increased contractility at the heart.
47
where do you find collagen I?
```
bone
tendon
skin
cornea
fascia
late wound repair
dentin
```
48
where do you find collagen II?
cartilage (hyaline too)
vitreous body @ eye
nucleus pulposus @ vertebrae
49
where do you find collagen III?
```
reticulin
skin
blood vessels
uterus
fetal tissue
granulation tissue
```
50
where do you find collagen IV?
basement membrane
basal lamina
lens @ eye
51
describe the types of collagen found in the eye
lens - IV
cornea - I
vitreous body - II
52
Osteogenesis Imperfecta I
AD
defect synthesis of collagen I (bone, tendon, dentin, skin, fascia, cornea, late wound repair) - problems forming triple helix
53
Ehlers-danlos, vascular type
defect in collagen III (reticulin, skin, blood vessels, uterus, fetus, granulation tissue) -- problems in cross linking collagen
54
Alport syndrome
defect in collagen IV (basement membrane, basal lamina, lens)
55
List the diseases where collagen is affected
OI
Ehlers Danlos
Alport
Good Pasture
56
Good Pasture
auto abs target type IV collagen (basement membrane, basal lamina, lens)
57
Describe the CXPX of OI type I
aka brittle bone disease
blue sclera: due to the reflection of the underlying choroidal veins through the thin sclera
pathological fractures at birth
deafness in some patients
58
CXPX of vascular type Ehlers Danlos
vascular and organ rupture
AD or AR
may be associated with joint dislocation, berry and aortic aneurysms, organ rupture
myxomatous degeneration can cause mitral valve prolapse (marfan too)
elastic skin + hypermobility of joints + increased bleeding tendency
goljan: hypermobile joints, aortic dissection (most common cause of death), mitral valve proplapse, bleeding into th eskin, ruture of the bowel, poor wound healing **can extend fingers so parallele with the extensor surface of the forearm - classical sign*
59
cxpx fo Alport Syndrome
nephritic syndrome - hypertension, increased BUN and creatinine, oliguria, hematuria, RBC casts in urine, proteinuria usually < 3.5
hereditary nephritis + sensorineural hearing loss + cataracts
(type IV collagen defect: basement membrane, basal lamina, lens)
60
OI again please, bit more organized this time
AD most commonly - decreased production of otherwise normal collagen type I (found at bone, skin, tendon, dentin, cornea, late wound healing).
sxs: MULTIPLE FRATURES with minimal trauma; may occur in birthing process + BLUE SCLERA due to the translucency of the connective tissue/sclera over the choroidal vessels + HEARING LOSS due to abnormal ossicles + DENTAL IMPERFECTIONS due to lack of dentin
61
Ehlers Danlos again please, but more organized this time
inheritance AD/AR and varies in severity and type
a) most common - hypermobility of joints
b) classical - joints and skin = defect in type V collagen
c) vascular type - skin and blood vessels = defect in type III collagen (uterus, fetal tissue, skin, bv, granulation tissue)
due to faulty collagen synthesis; inability to cross-link tropocollagen
presents with a) hyperextensible skin b) tendency to bleed and c) hypermobile joints
compliccations include: a) joint dislocation b) berry aneurysm c) aortic aneurysm and d) oragn rupture
62
Marfan Syndrome description time
AD fibrillin missense mutation chromosome 15
dilation fo ascending arota - dissection of aorta/aortic regurgitation; mitral valve prolapse -- conduction defects = sudden death; CARDIO DEFECTS DOMINATE
hypermobile joints, dislocation of lens (suspensory ligament is made of elastin); eucunoid proportions (arms longer than body; lower body longer than upper), arachnodactyly/spider hands
63
cxpx of aortic dissection
rfs: marfan, ehler danlos, HTN, pregos, coarctation of aorta
cystic medial degeneration - accumulation of breakdown products of elastin in the media
blood into weak points into the intima - will present as acute onset severe retrosternal chest pain radiating to the back; loss of upper extremity pulse due to compression fo subclavian artery by blood into the false lumen; can rupture into the pericardial sac, pleural or peritoneal cavities.
rupture usually occurs within 10 cm of AV
THORACIC @ marfans. abdominal --- syphilis??
64
amino acids in elastin?
nonhydroxylated (vrs collagen where lysine is OHd--requires vitamin C/scurvy) glycine, proline, lysine
65
lab test for gene expression
northern blot
66
confirmatory test for HIV after a positive ELISA
southern blot
67
use of microarrays
can detect single SNPs
copy number variants
= genotyping, clinical genetic testing, forensic analysis, genetic linkage analysis, cancer mutations
68
use fo karyotyping
chromosomal imbalances ie autosomal trisomies, sex chromosome disorders.
69
uses of FISH
specific localization of genes and direct visualization of anomalies/microdeletions when karyotype cant detect something so small
70
uses for the cre lox system
in ducibly manipulate genes at specific developmental points in order to study for example, a gene whose deletion causes embryonic death.
71
McCune Albright Syndrome description please
mutation in G protein signalling that would be fatal if occurs before fertilization as it would affect all cells. Mosaicism after this permits survival.
CXPX: a) unilateral café-au-lait spots, b) polyostic fibrous dysplasia, c) precocious puberty, d) multiple endocrine abnormalities
72
when would you suspect uniparental disomy
when an individual is showing a recessive disorder but only one parent is a carrier....so rare-zees
73
CXPX of Prader Willi
```
hypogonadism
hyperphagia -- obesity
short stature
neonatal hypotonia
intellectual disability
```
74
CXPX of Angelman Sydnrome
jerky, wide stance with arm flapping - ataxia - marionette
outbursts of inappropriate laughter - happy puppet
severe intellectual disability
seizures
75
Presentation of Mitochondrial Myopathies
```
myopathy
lactic acidosis
CNS disease
ragged red fibres on muscle bipsy
ex: Leber Hereditary Optic Neuropathy and **myoclonic epilepsy
```
76
newborn screening test for cystic fibrosis please
increased immunoreactive trypsinogen levels.
77
confirm diagnosis of Duchenne muscle dystrophy
increased CPK and increased aldolase
western blot and muscle biopsy -- will see fibrofatty replacement of skeletal and cardiac muscle due to lack of dystrophin connecting actin to alpha and beta dystroglycan leading to myonecrosis.
78
CXPX of Duchenne muscle dystrophy
pelvic girdle muscle weakness first that moves progressively superiorly
pseudohypertrophy of calf muscles - fibrofatty replacement
Gower maneuver - used of arms to stand
waddling gait
79
common cause of death in duchenne muscle dystrophy
dilated cardiomyopathy
80
why is becker less severe than duchenneÉ
non frameshift insertions so dystrophin is partially functional instead of truncated.
81
do deletions cause becker or duchenneÉ
both
82
name the acrocentric chromosomes and their significance
```
13,14,15,21,22
robertsonian translocation (long arms fuse at the centromeres if unbalanced -- miscarriage, stillbirth, chromosomal imbalances ie down syndrome or patau syndrome, etc.
```
83
```
severe intellectual disability
VSD
micrognathia
microcephaly
low set ears
prominent occiput
horeshoe kidney
rocker bottom feet
clenched fist with overlapping fingers
```
Edward Syndrome
| Trisomy 18
84
```
severe intellectual disability
microcephaly/holoProsencephaly
rocker bottom feet
polydactyly
VSD
cystic/horeshoe kidneys
cleft liP/Palate
cutis aplasia
fatal within one year of brith
```
Patua syndrome
Trisomy 13
cutis aplasia - congenital absence of skin.
85
```
moderate to severe intellectual disability
microcephaly
epicanthal folds
VSD
high-pitched crying/mewing
```
Cri-du- chat
5p deletion
chromosome 5 also FAP
86
```
intellectual disability
hypercalcemia
well developed verbal skills
extreme friendliness to strangers
supravalvular aortic stenosis
''elfin'' facies
```
Williams syndrome
7q deletion
chromosome 7 also CF
87
cleft palate
abnormal facies
cardiac defect
velocardiofacial syndrome
chromosome 22 microdeltion
problems with 3rd and 4th branchial pouches
88
thymus aplasia - no T cells
cardiac defects
hypocalcemia - secondary to parathyroid absnece
digeorge syndrome
chromosome 22q11
problems with 3rd and 4th branchial pouches
89
```
skin lesions
oedema cause lower plasma oncotic pressure
liver malfunction causes it fatty
anaemia
child with swollen abdomen
```
kwashiorkor - protein malnutrition
decreased protein intake
less apolipoproteins made is why fat accumulates in liver instead
90
decreased subcutaneous fat
tissue and muscle wasting
child
variable oedema
marasmus
| total calorie malnutrition
91
describe the pathophysiology of each clinical presentation of chronic alcholsim of the following list:
a) lactic acidosis
b) fasting hypoglycemia
c) hepatosteatosis
d) ketoacidosis
a) lactic acidosis because pyruvate to lactate uses up an NADH (that is in excess from OH metabolism to acetate)
b) fasting hypoglycemia because oxaloacetate to malate uses up an NADH; oxaloacetate cannot be used for gluconeogenesis
c) hepatosteatosis: TCA stopped bc makes NADH so lipogenesis is favoured AND dihydroxyacetone phosphate to glycerol 3 phosphate uses up an NADH that then combines with 4 FA to form TAGS (remember tis the back bone of TAGs)
d) ketoacidosis due to elevated ketogenesis that is favoured when the TCA an NADH producint cycle is shut down.
hurrah.
92
describe metabolism of OH in the peroxisome
alcohol --> + H2O2 with catalase --> acetaldehyde and water
93
describe metabolism of OH in the cytosol
alcohol --> alcohol dehydrogenase with NAD --> acetaldehyde and NADH
94
describe metabolism of OH in the microsome
alcohol --> NADPH with CYP2E1 --> acetaldehyte and NADPh
95
describe metabolism of OH in the mitochondria
acetaldehyde --> NAD + acetaldehyde dehydrogenase --> NADH and acetate
96
what is fomepizole
inhibits alcohol dehydrogenase in the cytosol
| use for ethylene or methanol poisoning.
97
list the metabolic pathways that occur in both the cytoplasm and the mitochoncria
heme synthesis
urea cycle
gluconeogenesis
98
list the metabolic pathways that occur in the cytosol only
```
glycolysis
fatty acid synthesis
HMP shunt
protein synthesis @ RER
steroid synthesis @ SER
cholesterol synthesis
```
99
list the metabolic pathwyas that occur in the mitochondria only
```
TCA cycle
ketogenesis
fatty acid beta oxidation
acetyl CoA production
oxidative phosphorylation
```
