disease (and a few other things) Flashcards
Gout
purine precipitate in joints, not pyrimidines bc pyrimidines are smaller (more soluble with 1 ring)
->uric acid accumulation
Lynch Syndrome (HNPCC)
mismatch repair problem (checking nucleotides during replication)
Xeroderma pigmentosum
TFIIH/NER problem
Abnormal pigmentation, cancer issues bc Pyrimidine (Thymine) dimer formation isn’t repaired with NER (nucleotide excision repair)
Cockayne Syndrome
TFII H problem, related to recognition/repair during transcription
->CNS disorder, short stature, premature aging
Cytosine is deaminated
Becomes Uracil
5-methylcytosine deamination
Becomes Thymine
alkylation of Guanine
O-CH3
O6-methylguanine -> binds thymine instead of cytosine
Repair: O6-meG methyltransferase (MGMT) in humans
Lesch-Nyhan
systemic accumulation of purines (similar to gout)
Neurological signs include poor muscle control and moderate mental retardation. These complications usually appear in the first year of life
Trichothiodystrophy
TFII H problem
- > brittle hair
- > intellectual impairment
Marfan Syndrome
abnormal splicing of fibrillin gene
-> Tall and prone to aneurysm
Abnormal splicing of CD44
Abnormal splicing of CD44 (cell-surface glycoprotein) is a predictor of tumor metastasis. Used as diagnostic and prognostic marker.
Beta-thalassemia
Mutation in DNA control Element
mutation problem within TATA box of beta-globin protein
->mild anemia
Not a disease
Beta globin + Alpha globin =
most common form of hemoglobin (iron containing protein within RBC)
Gamma-Delta-Beta thalassemia
Mutation DNA Control Element
Deletion of locus control region for beta-globin genes (BAD!!!!)
-MAJOR ANEMIA
Hemophilia B Leyden
Mutation DNA promoter region of clotting protein gene factor IX-> causes less transcription 1%
x-linked recessive, gets better at puberty -> 60% transctiption because promoter shared/overlapped with androgen receptor promoter site
-Clotting problem
Fragile X syndrome
Upstream DNA mutation of FMR1 causing excess (200+) CGG repeats -> CpG methylation (on islands) -> silencing of the gene FMR1
->mental retardation, enlarged testicles
craniosynostosis
Mutation of homeodomain protein (helix-turn-helix) MSX2-> hyperactive protein gain of function -> hyperexpression of gene that leads to suture (fontanelle) closure.
->mental retardation if not corrected surgically
Waardenburg Syndrome
MUTATION in sequence specific DNA binding protein
MITF gene mutation ->TF bHLH mutation -> plays a role in melanocyte development
->deafness, pigmentation defects (eyes and other stuff)
melanocyte
melanin producing cells; located in the bottom layer of the skin’s epidermis, the middle layer of the eye, the inner ear, meninges, bones, and heart.
Melanin is the pigment primarily responsible for skin color.
Androgen insensitivity syndrome
Androgen receptor ( zinc finger protein) inefficiency in either DNA binding domain or ligand binding domain ->downregulation of gene controlled by male androgens
->feminization/undermasculinization
Leukemia
hematopoietic (formation of blood cell components) disease/malignancy. Translocation of chromosome -> gain in function of proteins -> TF’s interact with and alter HAT’s/HDAC’s activity
HDAC = histone deacetylase HAT= histone acetyl transferase
Rubinstein-Taybi syndrome
HAT/HDAC problem
Mutation in 1 copy CREB Binding Protein gene (haploinsufficiency): CBP = HAT used in development
insufficiency =
->mental retardation, growth retarding, broad thumbs/toes, facial dismorphism
Scurvy
Deficiency in vit C
Vit C needed to mediate hydroxylation (-OH) of proline residues in collegen -> stabilizes collagen
-> weak connective tissue
Virus uses IRES and shuts down cap dependent translation
In some cases, the virus produces a protease that cleaves eIF4G, shutting down cap-dependent translation. The virus can continue using an IRES.
eIF4E and eIF4G cannot come together to promote translation.
Virus examples: HIV, poliovirus, Hep C, rhinovirus
mTOR works by ____
mTOR -> kinases -> phosphorylates 4EBP1 -> 4EBP1 no longer inhibits eIF4E -> upregulates translation
cancer and mTOR…
cancers upregulate mTOR
->less inhibition -> more translation
Rapamycin
shuts off mTOR (mammalian target of rapamycin)-> less kinase activity -> 4EBP1 not phosphorylated -> able to bind/inactivate eIF-4E
Clotting Disorders
Carboxylation (-COOH) of glutamate within prothrombin is needed for proper clotting.
Mediated by vit K
low vit K -> clotting disorder
Warfarin/coumadin
anticoagulant/clotting
works by targeting carboxylation (-COOH) of prothrombin (makes less carboxylation happen)
Works specifically by inhibiting recycling of Vit K
Congenital Disorder of Glycosylation (CDG)
post-translational disorder in adding carbohydrate to asparagine residues of proteins within cell membrane. Glycosylation needed to help hydrophillicity.
Common manifestations include ataxia; seizures; retinopathy; liver fibrosis; coagulopathies; failure to thrive; dysmorphic features
Prion disease
PrPc-> PrPsc
-Misfolded with many B sheets -> causes other PrPc’s to misfold -> amyloid plaques
Alzheimer’s disease
amyloid beta 42 is main culprit. Though increased AB40 also affects development
AB42 aggregates as plaques -> disruption/inflammation/tau protein tangles
-> nuerodegenerative -> memory loss/CNS trouble/trouble with motor/behavioral changes
Parkinson’s Disease
synuclein misfolds -> accumulation of lewy bodies in brain/spinal cord
Amyloidosis
Generalized protein misfolding that is systemic
->DMII, cardiac amyloidosis, ect.
Alpha-amanitin
Substance in death cap mushroom
Inhibits RNA Pol-II movement at bridge -> cannot translocate down DNA
->Liver/systemic damage = death
Rifampicin
Antibiotic: binds subunit of prokaryotic RNA polymerase and blocks its pooper (exit channel)
Tamoxifen
Competitive antagonist to estrogen at ER–>
binds estrogen receptor and doesn’t allow estrogen to bind correctly.
-> treatment in breast cancer (especially receptive positive BC in pre- menopausal women).
Antibiotic usual mode of inhibition??
This might not be right
Interfere with translation (tRNA/ribosomes/elongation)
avastin (bevacizumab)
human monoclonal antibody
angiogenisis inhbitor (formation of new blood vessels)
used to treat cancer
acetyl group
-COCH3
Li-Fraumeni syndrome
p53 mutation -> less inhibition of cell proliferation that has dmg that needs to be corrected -> increased probability of cancer
APC mutation
Axin/APC complex –l beta-catenin accumulation by phosphorylation by signaling ubiquitin- proteosome degradation pathway -> low cytoplasmic pool of b-catenin.
APC mutation destabilizes Axin/APC complex such that it doesn’t phosphorylate beta catenin -> b-catenin accumulation -> promotes upregulation in nucleus that causes proliferation ->increased likelyhood of COLON CANCER.
**Extracellular Wnt molecule is physiologic cell surface signal that causes inhibition of Axin/APC complex -> build up of b-catenin -> proliferation
Crohn’s Disease
peak onset age 15-30
Disease Ileum (always) and colon discontinous including upper GI transmural inflammation hematochezia RARE( Fistula's common
ALSO: strictures (narrowing), granuloma’s (collection of macrophages).
Risk Factors
-Smoker
Ulcerative Colitis
located rectum continuous pattern localized lower GI Fistula's Rare Mucosal inflammation hematochezia common
-former/non-smokers > risk
