First Aid: Biochemistry Flashcards
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?
Adenosine deaminase deficiency –> excess ATP and dATP builds up preventing DNA synthesis and toxic to lymphocytes
A patient has defective purine slavage due to absent HGPRT. How would they present and what would you use to treat?
Lesch-Nyhan Syndrome -
Hyperuricemia, Gout, Pissed off (aggression, self mutilation), Retardation, dysTonia
Tx: Allopurinol or febuxostat (2nd line)
A patient has defective purine slavage due to absent HGPRT. How would they present and what would you use to treat?
Lesch-Nyhan Syndrome -
Hyperuricemia, Gout, Pissed off (aggression, self mutilation), Retardation, dysTonia
Tx: Allopurinol or febuxostat (2nd line)
What happens if you are deficient in Xanthine Oxidase? Adenosine deaminase?
XO - uricemia and possibly gout
SCID from adenosine build up in lymphocytes
What could be used to inhibit DNA gyrase or prokaryotic topoisomerase III?
Fluoroquinolones
What disease exhibits a missense mutation in the DNA?
Sickel Cell (nucleotide substitution results in one changed amino acid)
What disease results from a frameshift mutation?
Duchenne muscular dystrophy
What disease result from defects in Nucleotide excision repair?
Xeroderma pigmentosum
What disease can result when there is a defect in DNA mismatch repair? What are such patients at risk for?
Hereditary nonpolyposis colorectal cancer (HNPCC)
Increased risk for ovarian and endometrial cancers
What disease results when DNA double stranded break repair is defective?
Ataxia telangiectasia
How can a drug be made to block DNA replication?
modified 3’OH end halts continued DNA synthesis
How could you halt mRNA synthesis using a natural chemical? What effect would this have in the human body?
alpha-Amanitin can black RNA pol II
causes severe hepatotoxicity if ingested
How could you halt mRNA synthesis using a natural chemical? What effect would this have in the human body?
alpha-Amanitin can black RNA pol II
causes severe hepatotoxicity if ingested
Where does mRNA quality control occur in the cell?
Cytoplasmic P-bodies (exonucleases, decapping enzymes, microRNAs are here)
Which antibodies are highly specific for SLE?
Anti-spliceosomal snRNPs (anti-Smith Abs)
Which antibodies are highly associated with mixed connective tissue disease?
Anti-U1 RNP (component of spliceosome)
Which end of the tRNA molecule binds the amino acid? Which side is responsible for ribosome binding? tRNA synthetase binding?
3’ CCA is amino acid acceptor site
T-arm (thymine, pseudouridine, cytosine) for tRNA ribosome binding
D-arm (dihydrouracil) - for tRNA synthetase binding
Which end of the tRNA molecule binds the amino acid? Which side is responsible for ribosome binding? tRNA synthetase binding?
3’ CCA is amino acid acceptor site
T-arm (thymine, pseudouridine, cytosine) for tRNA ribosome binding
D-arm (dihydrouracil) - for tRNA synthetase binding
What molecular compounds are responsible for tRNA charging and translocation?
ATP - activates (charges)
GTP - translocates (gripping going places)
What two very important regulators inhibit G1–> S cell cycle progression?
p53 and HYPOphosphorylated Rb
What are the Nissl bodies in neurons and what do they produce?
RER –> make peptide neurotransmitters for secretion
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?
Inclusion cell (I-cell) disease - inherited lysosomal storage disorder
defect in phosphotransferase enzyme –> failure to add Mannose-6-phosphate on glycoproteins in the Golgi
A patient has multiple defects in the ubiquitin-proteasome sytem, what may they be at risk of developing?
Parkinson Disease
A patient has multiple defects in the ubiquitin-proteasome sytem, what may they be at risk of developing?
Parkinson Disease
What proteins facilitate movement along the microtubules? What drugs can inhibit this movement?
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)
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?
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)
What drugs work directly on the sodium-potassium pump and what is their MoA?
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
Where are the four different types of collagen found and what diseases are related to them?
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
Where are the four different types of collagen found and what diseases are related to them?
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
Identify 3 key steps in the synthesis of collagen that can be disrupted and the disorder that will result?
- Hydroxylation of proline and lysine residues; requires Vitamin C –> SCURVY
- Triple helix formation –> Osteogenesis imperfecta
- Cross-linking outside of fibroblasts –> Ehlers-Danlos
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?
Osteogenesis Imperfecta –> autosomal dominant with decrease production of type I collagen
What are the 3 ways that Ehlers-Danlos syndrome can present?
- Hypermobility type (joint instability) - most common
- Classical type (easy bruising, hyperextensible skin and joint problems) - Type V collagen mutation
- Vascular type (vascular aneurysms and organ rupture) - typer III collagen deficiency
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?
Marfan Syndrome - defect in fibrillin, a glycoprotein that forms a sheath around elastin
Emphysema - alpha 1 antitrypsin deficiency –> increased elastase activity, breakdown of protein
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?
Marfan Syndrome - defect in fibrillin, a glycoprotein that forms a sheath around elastin
Emphysema - alpha 1 antitrypsin deficiency –> increased elastase activity, breakdown of protein
What are the various blotting procedures used for?
SNoW DRoP
Souther = DNA Northern = RNA Western = Protein
What is the specific type of initial screening test used to detect HIV?
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
What is the specific type of initial screening test used to detect HIV?
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
If you have a patient with a recessive disorder, despite confirming only one parent is a carrier, what could have occured?
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)
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?
Prader-Willi Syndrome - mother’s gene is silent and PATERNAL gene get’s deleted/mutated (usually chromsome 15) - 25 % cases from maternal UPD
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?
AngelMan Syndrome - dad’s gene normally silent then Maternal gene also gets deleted/mutated (chromosome 15)
5% of cases from paternal UPD
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?
AngelMan Syndrome - dad’s gene normally silent then Maternal gene also gets deleted/mutated (chromosome 15)
5% of cases from paternal UPD
Which family from GoT would be most at risk for AR disease?
Lannisters or Targaryens
What is an example of an X-linked dominant disorder?
Hypophosphatemic Rickets - increased phosphate wasting at proximal tubule (rickets like presentation)
What sort of genetic diseases will only be transmitted through the mother?
Mitochondrial inherited disease
e.g. Mitochondrial myopathies (myopathy, lactic acidosis and CNS disease) - muscle biopies show ragged red fibers
Which amino acids are necessary for purine synthesis?
Glycine, Aspartate, Glutamine
What two metabolic pathways is carbamoyl phosphate involved in?
Urea cycle and de novo pyrimidine synthesis
The formation of which compound necessary for DNA synthesis is impaired in orotic aciduria?
UMP
What does Leflunomide block?
Synthesis of orotic acid by inhibiting dihydroorotate dehydrogenase
