Cellular

Question 1

Carbamoyle Phosphate synthetase I and II

Answer 1

I: urea cycle
Mitochondria
Nitrogen source-ammonia

II: pyrimidine
Cytosolic
Nitrogen source: glutamine

Question 2

Leflunomide

Answer 2

Inhibits dihyrdroorate dehydrogenase

Pyrimidine synthesis

Question 3

Methotrexate
TMP
Pyrimethamine

Answer 3

Inhibit dihydrofolate reductase
–> decreased THF, INDIRECTLY blocking dUMP conversion to TMP
(Same action as 5 FU, but FU works directly)

Question 4

5 fluorouracil

Answer 4

Forms 5 F dump
Inhibits thymidylate synthase
Decreased dTMP
(Same site of action as methotrexate, TMP and Pyrimethamine)

Question 5

Orotic Aciduria

Answer 5

Deficiency in UMP synthase= Increased ortic acid in urine
Failure to thrive, developmental delay and MEGALOBLASTIC ANEMIA, refractory to Vit B12 and Folate supplementation 
NO HYPERAMMONEMIA (vs. ornithine transcarbomoylase) 
Tx: uridine supplementation

Question 6

Purine synthesis rate limiting enzyme

Answer 6

Glutamine PRPP amino transferase

Question 7

Azathioprine and 6 mercaptopurine

Answer 7

Inhibit de novo PURINE synthesis : block PRPP becoming IMP

Question 8

mycophenolate and ribavirin

Answer 8

Inhibit inosine mono phosphate dehydrogenase
Blocks conversion of IMP to GMP
PURINE synthesis

Question 9

hydroxyurea

Answer 9

Inhibits ribonucleotide reductase
Pyrimidine synthesis
UDP does not become dUDP

Question 10

Purine Salvage deficiencies

Answer 10

Adenosine deaminase deficiency

Leach Nyhan Syndrome

Question 11

Adenosine Deaminase deficiency

Answer 11

Increased dATP: toxicity in lymphocytes

Autosomal recessive SCID

Question 12

Leach Nyhan Syndrome

Answer 12

X linked, absent HGPRT(unable to salvage to GMP and IMP)
Excess uric acid production and de novo purine synthesis

S/s: self mutilation (lip biting), aggression, retardation, hyperuricemia, gout, dystonia
Tx: allopurinol
“Allie can’t salvage her friends. She’s a man so she bites her lip and does the robot. She ain’t retarded, she’s just pissed off.”

Question 13

Fluoroquinolones

Answer 13

Topoisomerase II and topoisomerase IV inhibitors

Question 14

Etoposide/teniposide

Answer 14

Eukaryotic topoisomerase II

Question 15

DNA polymerase III vs. polymerase I

Answer 15

Both: 5-3 synthesis and proofreads with 3-5 exonuclease
Prokaryotic
I: excises RNA primer with 5-3 exonuclease
III: does most of the transcription

Question 16

Telomerase

Answer 16

Eukaryotes only
RNA dependent DNA polymerase
adds DNA to 3 end

Question 17

Example of missense mutations

Answer 17

Sickle Cell disease (substitution of glutamic acid with valine)

Question 18

Frameshift

Answer 18

Deletion or insertion of nucleotides NOT DIVISIBLE BY 3
Ex: Duchenne’s muscular dystrophy
Tay Sach’s disease

Question 19

Lac operon

Answer 19

Activated when glucose is absent and lactose is available
Low glucose: increased CAP and increased transcription
High lactose: binds repressor protein: increase transcription

Question 20

Nucleotide excision repair

Answer 20

Endonuclease
Repairs bulky, helix distorting lesions
G1 phase of cell cycle
DEFECTIVE IN xeroderma pigmentosum

Question 21

Base excision repair

Answer 21

Spontaneous deamination 
Glycosylases remove base, creates an "AP" site
Nucleotides removed by Endonuclease
DNA poly fills gap 
Ligase seals

Question 22

Mismatch repair

Answer 22

Newly synthesized strand is recognized, mismatched nucleotides are removed
G2 phase of cell cycle
Defective in Lynch syndrome (HNPCC)

Question 23

Nonhomologous end joining

Answer 23

Repairs doubled stranded breaks
Mutated in ataxia telangiectasia (defect in ATM gene: failure to repair DNA double strand breaks: cell cycle arrest)
–cerebellar defects, spider angiomas, IgA deficiency
–increased AFP

Fanconi anemia (DNA repair defect causing bone marrow failure)

Question 24

Eukaryotic RNA polymerases

Answer 24

Poly I: rRNA
Poly II: mRNA
–inhibited by amanitin
Poly III: tRNA

Question 25

Prokaryotic RNA polymerase

Answer 25

1 polymerase makes all 3 types of RNA | Inhibited by Rifampin

Question 26

Splicing of pre mRNA: small nuclear ribonucleoproteins

Answer 26

Antibodies to snRNPs in Lupus

Question 27

Trna structure

Answer 27

5' CCA 3' end accepts amino acids | Cloverleaf

Question 28

Charging of tRNA

Answer 28

Aminoacyl -tRNA synthetase "matchmaker" Responsible for accuracy of amino acid selection

Question 29

Pyrimidine base synthesis rate limiting enzyme

Answer 29

Carbamoyl phosphate synthetase II

Question 30

Eukaryotic vs. prokaryotic ribosomes

Answer 30

EUK: 40S + 60S = 80S PRO: 30S + 50S = 70S

Question 31

Cell cycle phases

Answer 31

``` Regulated by cyclins, CDKs and tumor suppressors G1 (growth) S (DNA synthesis) G2 M/MITOSIS ```

Question 32

P53 function

Answer 32

Tumor suppressor Induces p21: inhibits CDK's --> hypophosphorylated Rb Rb then binds to and inactivates transcription factor E2F

Question 33

Permanent cells

Answer 33

Remain in G0, regenerate from stem cells

Question 34

Stable cells

Answer 34

Enter G1 from G0 when stimulated | Ex: hepatocytes and lymphocytes

Question 35

Nissl bodies

Answer 35

Rough ER in neurons

Question 36

I cell disease

Answer 36

Lysosomal storage disorder Defect in N-acetylglucosaminyl-1-phosphotransferase Golgi does not phosphorylate mannose residues --> proteins secreted extracellularly instead of being delivered to the lysosome. S/s : coarse facial features, clouded corneas, restricted joint movement, high plasma levels of lysosomal enzymes

Question 37

Peroxisome

Answer 37

Catabolism of very long chain fatty acids, blanched chain fatty acids, amino acids and ethanol

Question 38

Vimentin stain

Answer 38

Mesenchymal tissue | Ex: fibroblasts, endothelial cells, macrophages

Question 39

Desmin

Answer 39

Muscle | Rhabdomyosarcoma

Question 40

Cytokeratin

Answer 40

Epithelial cells | Squamous cell carcinoma

Question 41

GFAP

Answer 41

Neuroglia | Astrocytoma, glioblastoma

Question 42

Neurofilaments

Answer 42

Neurons | Neuroblastoma

Question 43

Drugs that act on microtubules

Answer 43

``` "Microtubules get constructed Very Poorly" Mebendazole Griseofulvin Colchicine Vincristine/vinblastine Paclitaxel ```

Question 44

Dynein vs. kinesin: molecular motor proteins

Answer 44

Dynein: retrograde to Microtubule- positive to negative Kinesin: anterograde negative to positive

Question 45

Cilia structure

Answer 45

9 + 2 arrangement of Microtubule doublets

Question 46

Kartagener Syndrome

Answer 46

Immotile cilia due to dynein arm defect Infertility due to immotile sperm and dysfunctional Fallopian tube cilia Can cause bronchiectasis, recurrent sinusitis, situs inversus

Question 47

Na/K ATPase

Answer 47

2K in / 3 Na out | ATP binding site is on cytosolic side of the membrane

Question 48

Inhibitors of sodium potassium pump

Answer 48

Ouabain: binds to K site Digoxin: directly inhibit Na/K ATPase: indirect inhibition of Na/Ca exchange --> increased cardiac contractility

Question 49

Collagen

Answer 49

``` A strong, slippery, bloody BM Type I: bone, skin, tendon Ex: osteogenesis imperfecta II: cartilage III: reticulin: Blood vessels Ex: vascular Ehlers-Danlos IV: Basement membrane --Alport syndrome --targeted by autoantibodies in Goodpastures syndrome ```

Question 50

Collagen structure

Answer 50

``` 1. Gly-X-Y X and y are proline or lysine 2. Hydroxylation: requires VIT C 3. Glycosylation --form triple helix --osteogenesis imperfecta 4. Exocytosis and proteolytic processing 5. Cross linking --ehlers-dahlia and Menkes disease ```

Question 51

Osteogenesis Imperfecta

Answer 51

``` Autosomal dominant Decreased production of type I collagen May be confused with CHILD ABUSE --multiple fractures --BLUE SCLERAE --hearing loss --tooth abnormalities ```

Question 52

Ehlers-Danlos

Answer 52

``` Auto Dom or recessive Faulty collagen synthesis Hyperextensible skin Tendency to bleed Berry and aortic aneurysms Organ rupture ```

Question 53

Menkes disease

Answer 53

X linked recessive connective tissue disease caused by impaired copper absorption and transport due to defective Menkes protein Brittle, kinky hair, growth retardation and hypotonia