Biochem - First Aid Flashcards by Andrew Herrmann

Inhibition of dihydroorotate dehydrogenase

Result?

Pathway?

Use?

Leflunomide

Inhibited conversion of carbamoyl phosphate into orotic acid

Pyrimidine synthesis

Rheumatoid arthritis

How well did you know this?

Not at all

Perfectly

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)

How well did you know this?

Not at all

Perfectly

Inhibition of ribonucleotide reductase

Result?

Uses?

Hydroxyurea

Inhibits DNA (purine and pyrimidine) synthesis

Melanoma, CML, sickle cell disease

How well did you know this?

Not at all

Perfectly

Inhibition of thymidylate synthase

Result?

5-fluorouracil

Inhibits synthesis of dTMP from dUMP (pyrimidine synthesis)

How well did you know this?

Not at all

Perfectly

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)

How well did you know this?

Not at all

Perfectly

Inhibition of conversion of PPRP to IMP

Result?

6-mercaptopurine, Azathioprine (pro-drug)

Inhibition of purine synthesis (IMP)

How well did you know this?

Not at all

Perfectly

Inhibition of inosine monophosphate dehydrogenase (2)

Result?

Use of Mycophenolate?

Mycophenolate, Ribavirin

Inhibition of purine synthesis (GMP)

Organ transplant prophylaxis

How well did you know this?

Not at all

Perfectly

Adenosine deaminase deficiency

Result?

SCID (autosomal recessive)

Impaired purine salvage –> build-up of dATP –> lymphocyte toxicity

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

Inhibition of xanthine oxidase (2)

Result?

Uses?

Allopurinol, Febuxostat

Inhibition of uric acid formation from hypoxanthine (purine degradation)

Lesch-Nyhan, Gout, others

How well did you know this?

Not at all

Perfectly

Increased excretion of uric acid

Probenecid

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

Inhibition of eukaryotic topoisomerase II

Etoposide, Teniposide

How well did you know this?

Not at all

Perfectly

Sickle cell disease…mutation type?

Missense (GLU –> VAL)

How well did you know this?

Not at all

Perfectly

Duchenne muscular dystrophy…mutation type?

Frameshift in DYSTROPHIN (X-recessive)

How well did you know this?

Not at all

Perfectly

Tay-Sachs…mutation type?

Frameshift in HEXOSAMINIDASE A

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

Deficient repair of double strand DNA breaks…diseases?

Ataxia telangiectasia (ATM), Fanconi anemia

How well did you know this?

Not at all

Perfectly

Alpha-amanitin

Function? Result?

Death cap mushrooms (Amanita phalloides)

Inhibits RNA polymerase 2 (DNA transcription) –> severe hepatotoxicity

How well did you know this?

Not at all

Perfectly

Inhibition of prokaryotic RNA polymerase ONLY

Inhibition of prokaryotic AND eukaryotic RNA polymerase

Rifampin

Actinomycin D

How well did you know this?

Not at all

Perfectly

Anti-Smith antibodies…what are they?

Antibodies to spliceosomal snRNPs

How well did you know this?

Not at all

Perfectly

Anti-U1 RNP antibodies…what are they?

What disease?

Antibodies to a specific spliceosomal snRNP (snRNP70)

Mixed connective tissue disease

How well did you know this?

Not at all

Perfectly

Which ribosome subunits are eukaryotic vs prokaryotic?

How to remember?

Eukaryotic = 40S and 60S
Prokaryotic = 30S and 50S

Eukaryotes = Even
prOkaryotes = Odd

How well did you know this?

Not at all

Perfectly

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?

1. 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

Biochem - First Aid Flashcards

(67 cards)