Nucleotide Nuisances
What type of anemia would hereditary orotic aciduria most likely cause?
Megaloblastic anemia (we’re not making pyrimidines)
Name the essential and conditionally essential amino acids!
PVT TIM HILL
Cys, Arg, Tyr
Deficiency of tetrahydrobiopterin (BH4) - what disease?
Phenylketonuria (PKU)
The two amino acids that can be made from oxaloacetate?
Aspartate and Asparagine
Which CF mutation class is a “conduction mutation”?
Class IV
What enzyme is usually deficient in patients with Severe Combined Immunodeficiency Syndrome (SCID)?
Adenosine Deaminase (ADA)
What are the only two amino acids that are purely ketogenic?
Lysine, Leucine
The transaminase that converts glyoxylate to glycine is deficient. What major symptom would you see?
Kidney stones (primary oxaluria type 1)
What two vitamins are required for metabolism of Threonine through TCA?
B7 and B12
Which of these compounds is DECREASED in CF cells?
A. NADPH
B. Superoxide dismutase
C. PFK-1
D. G6PDH
NADPH
Ribonucleotide Reductase - what type of nucleotides does it catalyze, and what cofactor does it require?
RNR can only work on NDPs (two phosphates), and it requires thioredoxin.
MNEMONIC: CUGA
Patient with methylmalonic acidemia - WHAT VITAMIN DEFICIENCY DO YOU ALWAYS THINK OF
B12 (please remember this forever)
Type 1 Homocystinuria - What's deficient? What accumulates? What are the symptoms?
Deficient in cystathionine β-synthase, accumulate homocysteine (and serine), key symptoms are subluxation of the lens, osteoporosis, and premature CVD!
Glutamate semialdehyde can be converted to what two amino acids (besides glutamate)?
Proline or Ornithine
Which of these is NOT a correct treatment for the lung symptoms in a CF patient?
A. Chest physiotherapy
B. Osmotic agents
C. DNAse I
D. Inhaled hypotonic saline
Hypotonic saline
This drug is a suicide inactivator of thymidylate synthase.
What is “5-fluorouracil”?
Name the 3 series of reactions needed to convert 3-PG to Serine
Oxidize, transaminate, hydrolyze phosphate
54 y/o male presents to the clinic with fatigue and painful movement. Urinalysis reveals black urine, and tissue biopsy reveals dark discoloration of joints. What metabolite accumulated?
Homogentisate!
A 27 year-old female prescribed a selective-serotonin reuptake inhibitor is increasing the bioavailability of a molecule made from what amino acid?
Tryptophan
Name a drug that is a potentiator-only CFTR modulator?
Ivacaftor
List the two major regulators of aspartate transcarbamylase (one activates, one inhibits). Which direction does each one shift the graph of ATC kinetics?
ATP activates ATC (too many purines, make pyrimidines) - left shift
CTP inhibits ATC (too many pyrimidines, stop pyrimidines) - right shift
Deficiency of ONE of the following vitamins would NOT cause accumulation of BCAAs?
B1
B2
B3
B7
B9
B9
Note BCAA Dehydrogenase Complex Vitamins, plus VOMIT vitamins!
You read a clinical vignette and you see the following buzzwords: A 2 year-old child aggressively bites their lips such that they're bleeding, and they also bite their nails. Examination reveals what looks like orange sand in their diaper. This child has a defect in which metabolic pathway?
A. Purine synthesis
B. Purine degradation
C. Purine salvage
D. Pyrimidine synthesis
E. Pyrimidine degradation
F. Pyrimidine salvage
Purine salvage (HGPRT!)
A 38 year-old male receives laboratory testing the day of his clinic visit and is found to have elevated VMA and HVA in his urine via a dipstick analysis. What medication could be helpful for this patient?
MAO Inhibitors
What is the best treatment for the most common mutation affecting CF patients?
A. Read-through compounds
B. Correctors
C. Potentiators
D. Transcription Inducers
Correctors!