First Aid: Biochemistry

Question 1

A 6 month old presents with recurrent infections. T-cells, B-cells and gammaglobulins are all low (especially low lymphocytes). What could be the cause of this?

Answer 1

Adenosine deaminase deficiency –> excess ATP and dATP builds up preventing DNA synthesis and toxic to lymphocytes

Question 2

A patient has defective purine slavage due to absent HGPRT. How would they present and what would you use to treat?

Answer 2

Lesch-Nyhan Syndrome -

Hyperuricemia, Gout, Pissed off (aggression, self mutilation), Retardation, dysTonia

Tx: Allopurinol or febuxostat (2nd line)

Question 3

A patient has defective purine slavage due to absent HGPRT. How would they present and what would you use to treat?

Answer 3

Lesch-Nyhan Syndrome -

Hyperuricemia, Gout, Pissed off (aggression, self mutilation), Retardation, dysTonia

Tx: Allopurinol or febuxostat (2nd line)

Question 4

What happens if you are deficient in Xanthine Oxidase? Adenosine deaminase?

Answer 4

XO - uricemia and possibly gout

SCID from adenosine build up in lymphocytes

Question 5

What could be used to inhibit DNA gyrase or prokaryotic topoisomerase III?

Answer 5

Fluoroquinolones

Question 6

What disease exhibits a missense mutation in the DNA?

Answer 6

Sickel Cell (nucleotide substitution results in one changed amino acid)

Question 7

What disease results from a frameshift mutation?

Answer 7

Duchenne muscular dystrophy

Question 8

What disease result from defects in Nucleotide excision repair?

Answer 8

Xeroderma pigmentosum

Question 9

What disease can result when there is a defect in DNA mismatch repair? What are such patients at risk for?

Answer 9

Hereditary nonpolyposis colorectal cancer (HNPCC)

Increased risk for ovarian and endometrial cancers

Question 10

What disease results when DNA double stranded break repair is defective?

Answer 10

Ataxia telangiectasia

Question 11

How can a drug be made to block DNA replication?

Answer 11

modified 3’OH end halts continued DNA synthesis

Question 12

How could you halt mRNA synthesis using a natural chemical? What effect would this have in the human body?

Answer 12

alpha-Amanitin can black RNA pol II

causes severe hepatotoxicity if ingested

Question 13

How could you halt mRNA synthesis using a natural chemical? What effect would this have in the human body?

Answer 13

alpha-Amanitin can black RNA pol II

causes severe hepatotoxicity if ingested

Question 14

Where does mRNA quality control occur in the cell?

Answer 14

Cytoplasmic P-bodies (exonucleases, decapping enzymes, microRNAs are here)

Question 15

Which antibodies are highly specific for SLE?

Answer 15

Anti-spliceosomal snRNPs (anti-Smith Abs)

Question 16

Which antibodies are highly associated with mixed connective tissue disease?

Answer 16

Anti-U1 RNP (component of spliceosome)

Question 17

Which end of the tRNA molecule binds the amino acid? Which side is responsible for ribosome binding? tRNA synthetase binding?

Answer 17

3’ CCA is amino acid acceptor site

T-arm (thymine, pseudouridine, cytosine) for tRNA ribosome binding

D-arm (dihydrouracil) - for tRNA synthetase binding

Question 18

Which end of the tRNA molecule binds the amino acid? Which side is responsible for ribosome binding? tRNA synthetase binding?

Answer 18

3’ CCA is amino acid acceptor site

T-arm (thymine, pseudouridine, cytosine) for tRNA ribosome binding

D-arm (dihydrouracil) - for tRNA synthetase binding

Question 19

What molecular compounds are responsible for tRNA charging and translocation?

Answer 19

ATP - activates (charges)

GTP - translocates (gripping going places)

Question 20

What two very important regulators inhibit G1–> S cell cycle progression?

Answer 20

p53 and HYPOphosphorylated Rb

Question 21

What are the Nissl bodies in neurons and what do they produce?

Answer 21

RER –> make peptide neurotransmitters for secretion

Question 22

A 5 year old boy presents with coarse facial features, clouded corneas and restricted joint movement. Laboratory tests reveal high plasma levels of lysosomal enzymes. What cellular defect led to this disorder?

Answer 22

Inclusion cell (I-cell) disease - inherited lysosomal storage disorder

defect in phosphotransferase enzyme –> failure to add Mannose-6-phosphate on glycoproteins in the Golgi

Question 23

A patient has multiple defects in the ubiquitin-proteasome sytem, what may they be at risk of developing?

Answer 23

Parkinson Disease

Question 24

A patient has multiple defects in the ubiquitin-proteasome sytem, what may they be at risk of developing?

Answer 24

Parkinson Disease

Question 25

What proteins facilitate movement along the microtubules? What drugs can inhibit this movement?

Answer 25

Dynein - retrograde Kinesin - anterograde Microtubules Get Constructed Very Poorly- Mebendazole (anti-helminthic), Griseofulvin (anti-fungal), Colchicine (anti-gout), Vincristine/Vinblastine (anti-cancer), Paclitaxel (anti-cancer)

Question 26

A 4 year old patient presents with bronchiectasis. He has a history of recurrent sinus infections. PMI is palpated at the right lower sternal border. What are they at risk of developing?

Answer 26

Kartagener syndrome (primary ciliary dyskinesia) - immotile cilia due to dynein arm defect Risk for infertility due to immotile sperm (dysfunctional fallopian tube cilia in females)

Question 27

What drugs work directly on the sodium-potassium pump and what is their MoA?

Answer 27

Ouabain inhibits by binding K+ site Cardiac glycosides (digoxin and digitoxin) directly inhibit Na+-K+ ATPase --> inhibiting Na+/Ca exchange --> increased intracellular Ca --> increased cardiac contractility

Question 28

Where are the four different types of collagen found and what diseases are related to them?

Answer 28

Be (So Totally) Cool, Read Books Type I - B(ONE), Skin, Tendon - decreased production in osteogenesis imperfecta type 1 Type II -- CarTWOlage Type III - Reticulin, blood vessels - Vascular type of Ehlers-Danlos syndrome (ThreE D) Type IV - Basement membrane, "under the floor" - defective in Alport syndrome and targeted by autoantibodies in Goodpasture syndrome

Question 29

Where are the four different types of collagen found and what diseases are related to them?

Answer 29

Be (So Totally) Cool, Read Books Type I - B(ONE), Skin, Tendon - decreased production in osteogenesis imperfecta type 1 Type II -- CarTWOlage Type III - Reticulin, blood vessels - Vascular type of Ehlers-Danlos syndrome (ThreE D) Type IV - Basement membrane, "under the floor" - defective in Alport syndrome and targeted by autoantibodies in Goodpasture syndrome

Question 30

Identify 3 key steps in the synthesis of collagen that can be disrupted and the disorder that will result?

Answer 30

1. Hydroxylation of proline and lysine residues; requires Vitamin C --> SCURVY 2. Triple helix formation --> Osteogenesis imperfecta 3. Cross-linking outside of fibroblasts --> Ehlers-Danlos

Question 31

A newborn presents with multiple fractures immediately after the birthing process. Xray reveals skeletal deformity and limb shortening. The newborn also has blue sclerae and doesn't respond to any sound. What disease is this?

Answer 31

Osteogenesis Imperfecta --> autosomal dominant with decrease production of type I collagen

Question 32

What are the 3 ways that Ehlers-Danlos syndrome can present?

Answer 32

1. Hypermobility type (joint instability) - most common 2. Classical type (easy bruising, hyperextensible skin and joint problems) - Type V collagen mutation 3. Vascular type (vascular aneurysms and organ rupture) - typer III collagen deficiency

Question 33

Elastin is stretchy protein within the skin, lungs arteries, and vertebrae. What are two diseases that are associated with this protein and can lead to serious complications?

Answer 33

Marfan Syndrome - defect in fibrillin, a glycoprotein that forms a sheath around elastin Emphysema - alpha 1 antitrypsin deficiency --> increased elastase activity, breakdown of protein

Question 34

Elastin is stretchy protein within the skin, lungs arteries, and vertebrae. What are two diseases that are associated with this protein and can lead to serious complications?

Answer 34

Marfan Syndrome - defect in fibrillin, a glycoprotein that forms a sheath around elastin Emphysema - alpha 1 antitrypsin deficiency --> increased elastase activity, breakdown of protein

Question 35

What are the various blotting procedures used for?

Answer 35

SNoW DRoP ``` Souther = DNA Northern = RNA Western = Protein ```

Question 36

What is the specific type of initial screening test used to detect HIV?

Answer 36

Indirect ELISA - uses a test antigen to see if anti-HIV antibodies are present in patients blood Direct ELISA - uses a test antibody to see if specific antigens are present in patient's blood

Question 37

What is the specific type of initial screening test used to detect HIV?

Answer 37

Indirect ELISA - uses a test antigen to see if anti-HIV antibodies are present in patients blood Direct ELISA - uses a test antibody to see if specific antigens are present in patient's blood

Question 38

If you have a patient with a recessive disorder, despite confirming only one parent is a carrier, what could have occured?

Answer 38

Uniparental disomy (UPD) Results from error in meiosis I or II, where you get 2 copies of a chromosome from 1 parent and no copies from the other (i.e. - Euploid number of chromosomes)

Question 39

A patient presents with hyperphagia and obesity. You find they are intellectually disabled and physical exam reveals hypogonadism and low muscle tone. What is the disorder and how did it originate?

Answer 39

Prader-Willi Syndrome - mother's gene is silent and PATERNAL gene get's deleted/mutated (usually chromsome 15) - 25 % cases from maternal UPD

Question 40

A young female patient presents with seizures and ataxia. They have severe intellectual disability and the mother complains of frequent inappropriate laughter. What may be the cause of this?

Answer 40

AngelMan Syndrome - dad's gene normally silent then Maternal gene also gets deleted/mutated (chromosome 15) 5% of cases from paternal UPD

Question 41

A young female patient presents with seizures and ataxia. They have severe intellectual disability and the mother complains of frequent inappropriate laughter. What may be the cause of this?

Answer 41

AngelMan Syndrome - dad's gene normally silent then Maternal gene also gets deleted/mutated (chromosome 15) 5% of cases from paternal UPD

Question 42

Which family from GoT would be most at risk for AR disease?

Answer 42

Lannisters or Targaryens

Question 43

What is an example of an X-linked dominant disorder?

Answer 43

Hypophosphatemic Rickets - increased phosphate wasting at proximal tubule (rickets like presentation)

Question 44

What sort of genetic diseases will only be transmitted through the mother?

Answer 44

Mitochondrial inherited disease e.g. Mitochondrial myopathies (myopathy, lactic acidosis and CNS disease) - muscle biopies show ragged red fibers

Question 45

Which amino acids are necessary for purine synthesis?

Answer 45

Glycine, Aspartate, Glutamine

Question 46

What two metabolic pathways is carbamoyl phosphate involved in?

Answer 46

Urea cycle and de novo pyrimidine synthesis

Question 47

The formation of which compound necessary for DNA synthesis is impaired in orotic aciduria?

Answer 47

UMP

Question 48

What does Leflunomide block?

Answer 48

Synthesis of orotic acid by inhibiting dihydroorotate dehydrogenase