Biochem - First Aid Flashcards
Inhibition of dihydroorotate dehydrogenase
Result?
Pathway?
Use?
Leflunomide
Inhibited conversion of carbamoyl phosphate into orotic acid
Pyrimidine synthesis
Rheumatoid arthritis
Inactive/mutate UMP synthase
Result? Pathway?
Symptoms?
IF hyperammonemia instead of refractory anemia?
Orotic aciduria
Inhibited conversion of orotic acid to UMP (pyrimidine synthesis)
Orotic acid in urine, megaloblastic anemia refractory to folate and B12 supplementation
Ornithine transcarbamylase deficiency (urea cycle)
Inhibition of ribonucleotide reductase
Result?
Uses?
Hydroxyurea
Inhibits DNA (purine and pyrimidine) synthesis
Melanoma, CML, sickle cell disease
Inhibition of thymidylate synthase
Result?
5-fluorouracil
Inhibits synthesis of dTMP from dUMP (pyrimidine synthesis)
Inhibition of dihydrofolate reductase (3)
Result?
Methotrexate, Trimethoprim, Pyrimethamine
Inhibition of restoration of THF from DHF, thus inhibition of dTMP formation from dUMP (thymidylate synthase)
Inhibition of conversion of PPRP to IMP
Result?
6-mercaptopurine, Azathioprine (pro-drug)
Inhibition of purine synthesis (IMP)
Inhibition of inosine monophosphate dehydrogenase (2)
Result?
Use of Mycophenolate?
Mycophenolate, Ribavirin
Inhibition of purine synthesis (GMP)
Organ transplant prophylaxis
Adenosine deaminase deficiency
Result?
SCID (autosomal recessive)
Impaired purine salvage –> build-up of dATP –> lymphocyte toxicity
Intellectual disability, self-mutilation, aggression, hyperuricemia, orange crystals in diaper, gout, dystonia
Cause?
Result?
Lesch-Nyhan syndrome
HGPRT deficiency
Impaired purine salvage (hypoxanthine, guanine) –> excessive uric acid and de novo purine synthesis
Inhibition of xanthine oxidase (2)
Result?
Uses?
Allopurinol, Febuxostat
Inhibition of uric acid formation from hypoxanthine (purine degradation)
Lesch-Nyhan, Gout, others
Increased excretion of uric acid
Probenecid
Inhibition of prokaryotic topoisomerase II and IV
Other name of topoisomerase II
Normal function?
Fluoroquinolones
DNA gyrase
Add single or double strand breaks in DNA helix during replication fork formation to avoid supercoils
Inhibition of eukaryotic topoisomerase II
Etoposide, Teniposide
Sickle cell disease…mutation type?
Missense (GLU –> VAL)
Duchenne muscular dystrophy…mutation type?
Frameshift in DYSTROPHIN (X-recessive)
Tay-Sachs…mutation type?
Frameshift in HEXOSAMINIDASE A
Deficient nucleotide excision repair…disease?
Defect?
When does this usually happen?
Xeroderma pigmentosum
Endonuclease –> can’t remove damaged DNA bases (UV light) –> neoplasia
G1 phase
Deficient mismatch repair…disease?
What does this mean?
Genes mutated?
When does this usually happen?
Lynch syndrome (HNPCC)
Can’t remove mismatched nucleotides after DNA synthesis –> neoplasia (ascending colon, endometrium, other)
MSH, MRH
G2
Deficient repair of double strand DNA breaks…diseases?
Ataxia telangiectasia (ATM), Fanconi anemia
Alpha-amanitin
Function? Result?
Death cap mushrooms (Amanita phalloides)
Inhibits RNA polymerase 2 (DNA transcription) –> severe hepatotoxicity
Inhibition of prokaryotic RNA polymerase ONLY
Inhibition of prokaryotic AND eukaryotic RNA polymerase
Rifampin
Actinomycin D
Anti-Smith antibodies…what are they?
Antibodies to spliceosomal snRNPs
Anti-U1 RNP antibodies…what are they?
What disease?
Antibodies to a specific spliceosomal snRNP (snRNP70)
Mixed connective tissue disease
Which ribosome subunits are eukaryotic vs prokaryotic?
How to remember?
Eukaryotic = 40S and 60S Prokaryotic = 30S and 50S
Eukaryotes = Even prOkaryotes = Odd
Permanent cell types
Neurons, skeletal muscle, cardiac muscle, RBCs
Stable cell types
Hepatocytes, lymphocytes
Labile cell types
Importance?
BM, gut epithelium, skin, hair follicles, germ cells
MOST affected by chemotherapy
Coarse facial features, clouded corneas, restricted joint movement, high plasma levels of lysosomal enzymes
Explain
I-Cell Disease
Defect in N-acetylglucosaminyl-1-phosphotransferase
Failure of Golgi to add mannose-6-phophate to lysosome-bound enzymes –> get released into extracellular space
Vimentin
Desmin
Cytokeratin
GFAP
Neurofilaments
Mesenchymal tissue (ex. sarcoma)
Muscle (ex. rhabdomyosarcoma)
Epithelial (ex. SCC)
Neuroglia (astrocytoma, glioblastoma)
Neurons (ex. neuroblastoma)
Drugs that inhibit microtubules (6)
Mebendazole (helminth) Griseofulvin (fungal) Colchicine (gout) Vincristine (cancer) Vinblastine (cancer) Paclitaxel (cancer)
2 molecular motor proteins
What do they do?
Dynein (retrograde), Kinesin (anterograde)
Move things along the microtubule
Defective dynein (ATPase) in cilia
Kartagener syndrome (primary ciliary dyskinesia)
Inhibition of K+ binding site of Na-K ATPase
Ouabain
Direct inhibition of the Na-K ATPase
Result?
Cardiac glycosides (digoxin, digitoxin)
Inhibition of Na/Ca exchanger –> increased Ca++ –> increased cardiac contractility
Deficient type 1 collagen
Where is it used?
Osteogenesis imperfecta type 1
Bone, skin, tendon, dentin, fascia, cornea, late wound repair
Deficient type 3 collagen
Where is it used?
Ehlers-Danlos (vascular type) – vascular and organ rupture symptoms
Skin, BLOOD VESSELS, uterus, fetal tissue, granulation tissue
Deficient/destroyed type 4 collagen (2)
Where is it used?
Alport syndrome, Goodpasture syndrome
Basement membrane, basal lamina, lens
Deficient hydroxylation of proline and lysine residues
What process?
Scurvy (requires Vitamin C as cofactor)
Collagen synthesis
Deficient glycosylation of pro-alpha-chain hydroxylysine residues (forming triple helix)
Genes?
What process?
Osteogenesis imperfecta
COL1A1, COL1A2
Collagen synthesis (procollagen formation)
Deficient lysine-hydroxylysine cross-linking (2)
Enzyme? Needs what?
What process?
Ehlers-Danlos, Menkes disease
Lysyl oxidase – needs COPPER
Collagen synthesis (collagen fibril formation)
Deficient type 5 collagen
Ehlers-Danlos (classical type) – joint and skin symptoms
Brittle kinky hair, growth retardation, tortuous arteries, hypotonia
Cause?
Findings?
Menkes disease
ATP7A mutation –> impaired copper absorption and transport –> dysfunctional lysyl oxidase –> poor collagen
Low ceruloplasmin
Defect in a glycoprotein that forms a sheath around elasin
What is the defect?
Marfan syndrome
Fibrillin
Excessive elastase (elastin breakdown) activity
Alpha-1 antitrypsin deficiency
Decreased production of collagen and elastin in the skin over time
Wrinkles (aging)
PCR commonly used to diagnose what? (2)
Neonatal HIV, herpes encephalitis
Confirmatory test for HIV after ELISA
Western blot
Ordering, numbering, and staining chromosomes during metaphase
Karyotyping
Lab electrophoresis test between a protein and a DNA probe
Southwestern blot
Blood group alleles are a good example of ____
Codominance (both contribute to phenotype)
2 patients with NF1 have different degrees of the disease
Variable expressivity
Not everyone with the BRCA1 mutation has breast cancer
Incomplete penetrance
Mutations in PKU, Marfans, and CF cause a wide variety of symptoms across multiple organ systems
Pleiotropy
The onset of Huntington’s gets earlier each generation
Anticipation
A patient with an inherited RB mutation eventually develops a full-on retinoblastoma or osteosarcoma
Loss of heterozygosity
Unilateral brown macules on skin
Malformation of bones
Precocious puberty
Endocrine anomalies
If alive, what must be the case?
Mutation?
McCune-Albright syndrome
Must be a MOSAIC (fatal if before fertilization)
Mutated G-protein signaling
A patient w/ Downs syndrome tests negative, then later tests positive on skin cell sampling…explanation?
MOSAIC (1-3% of cases)
Presence of normal AND mutated mitochondrial DNA, causing variable expressivity of mtDNA disease
Heteroplasmy
X-linked recessive disease…
- Frequency of the disease in males?
- Frequency of the disease in females?
Males = q Females = q^2
Hyperphagia, obesity, intellectual disability, hypogonadism, hypotonia
Causes?
Prader-Willi syndrome
75% = Imprinting of maternal gene, loss of paternal gene 25% = Uniparental disomy (both imprinted maternal genes)
Inappropriate laughter, seizures, ataxia, intellectual disability
Causes?
Angelman syndrome
95% = Imprinting of paternal gene, loss of maternal gene 5% = Uniparental disomy (both imprinted paternal genes)
Imprinting…what is it?
Cytosine methylation of a gene, thus silencing it
Diseases of ____ are often pleotropic and variably expressed
Autosomal dominant
Ragged red fibers…inheritance?
Mitochondrial
Algorithm for determining inheritance pattern?
- Is parent affected? (Y = dominant, N = recessive)
2a. Male to male transmission? (Y = Auto dominant, N = X-Dominant)
2b. All/mostly males? (Y = X-recessive, N = auto recessive)
Short stature, normal head/torso
Mutation? Inheritance?
Achondroplasia
FGFR3 – autosomal dominant
**How does alcohol consumption cause hypoglycemia?
Uses NAD+ to be metabolized to acetic acid. Low NAD+ and high NADH cause impaired gluconeogenesis due the shift of 3 metabolic reactions…
- DHAP --> glycerol-3P - Pyruvate --> lactate - Oxaloacetate --> malate
