Review Session Terms I should Know Flashcards
Adheren Junction (what is made it made of)
cell-cell (homophilic) and cell-ECM interactions (heterophillic)
actin-actin interaction and actin-intermediate filament interaction
Desmosome (what is made it made of)
cadherin, desmoplakin linker protein, and intermediate filament
Hemidesmosome (what is made it made of)
- integrin a6/b4, desmoplakin like protein, and intermediate filament
- binds to the ECM
Pemiphagus
autoimmune attacking on your caderhins
Ehlar Danlos Syndrome
mess up (defect) in keratin intermediate filament assembly (stretchy skin)
Type IV collagen
-type of collagen forms a meshwork in basal lamina (can not form fibrils)
Basal Laminin
- made of Type IV collagen, lamilln, and proteoglycan
- function in muscle, kidney filter, and regulates cell proliferation
what are the mechanisms of converting proto-oncogene to oncogene?
- point mutations
- gene amplification
- chromosomal rearrangement
DNA Viruses can cause cancer by
expressing genes in their genome that block action of Rb and p53
Malignant cancer (invasive) are a result of
a series of mutations (ie. LOF of p53 and mutation of Ras that makes it overactive)
Steroid for some genes act as
partner transcription factors to activate gene expression
CAM kinases are aka
calmodulin (ie. Myosin light chain Kinase)
JAK-STAT is
is a type of Receptor tyrosine but lacks the kinase activity (no transphorylation)
cyclin subunit is turned off during the end of mitosis by
ubiquitination via E3 ligase
cyclin +regulatory unit=
complete cyclin-dependent Kinase (cdk)
once cyclin was binds to regulatory unit your have inhibitory and activating kinase called
wee1 and activating kinase(cak)
For a resistant virus to to proliferate in patient the HIV protease should have
both a higher Ki than the wild type (can’t bind the inhibitor well) and kcat/km near wild-type level (can process polyprotein)
2 ways in which you can have HIV drug failure is.. what is the solution?
Patient may clear drug too rapidly
Patient has poor compliance
-solution is to change to different drugs that can help (hopefully some that can reduce ADRs and also fight virus)
One big difference between HIV and HCV in why HIV persists in your body while though expensive in treatment HCV can be completely cleared from your body is…
HIV can integrate into your genome, HCV doesn’t.
Dendritic cells
- APCs
- activate naive T cells
- FDCs provide aid in the maturity of B cells providing cytokines during during its migration to the periphery
Importance differences BCR and TCR
- TCR aren’t secreted
- TCR doesn’t undergo somatic hypermutation
What are super-antigens?
bacterial proteins that link the MHC molecule and TCR (variable B genes of it) together. Stimulating substantial cytokine signaling than the conventional Ag.
What is an important reaction needed between the Tcell and target (B cells, APC [DC])
- CD40 (on the Tcell target)-CD40L (on Tcell)
- B7-CD28
- TCR-Ag-MHC
Heterotaxy
- Solitus ambiguous
- mix in normal and abormal laterality (due to morphogen on both sides of embryo
During Implantation
-trophoblast cells attach to the wall of the endometrium (uterine lining)
Spina bifida (surgical repairable) or anenchephaly (fatal) occurs due to defect in
neural plate closure
Birth Defects are most sensitive at weeks
3-8
Birth defects can be induced by
Environment (alcohol and drugs, viruses) and pharmacologic products and genetics.
asymmetric flow is able to move from right to left axis due to morphogen flow via
ciliated epithelium (pushed by calcium release)
Epidermolysis Bullosa
inability to synthesize intermediate filaments like desmosomes and hemi-desmosomes (blistered skin)
laminin does what?
- cross-linker protein
- apart of Basal lamina
- aids in wound healing and clots
Fibroconnectin
- cross linker proteins
- apart of basal lamina
Mechanisms of Enzyme Regulation
1) Allosteric regulation
2) Reversible modification
3) Irreversible Modification
4) Protein-Protein interactions
Allosteric regulation and an example
modulator binds at site away from active site, affecting its activity
ie. ATcase with ATP increasing its activity (activator of the R state) and CTP decreasing its acitvity (inhibitor which favors the T state
Reversible Modification
alter enzyme by causing conformational change that affects catalysis (conformation) or altering cellular localization of enzyme
ie. phosphorylation via kinase is a important one
Irreversible modification
covalent modification
ie. Zymogen are synthesized (inactive form) and are activated irreversibly at the time and place where they are needed, clotting cascade (factor proteins are serine proteases)
Regulation of Protein-Protein Interactions
ie. Anti-Thrombin, Pancreatic Anti-tryspin, and alpha 1-anti-trypsin
zymogen activation though irreversible, can interact with inhibitor proteins (plasmin), calmodulin binding interactions with other proteins via Ca2+ binding.
Clotting protein via this enzyme causes the clotting protein to form with gamma carboxy glutamate, allowing binding to the phospholipid….
What drugs inhibit this enzyme
Vitamin K dependent Protein
Anti-coagulants (ie. Warfarin)- slowing clotting
After rapid clotting formation, localization to the site of injury, you then get rapid termination via..
plasminogen conversion to plasmin. Plasmin is a reversible inhibitor or zymogen activation which acts to hydrolyze and remove the fibrin clot.
The best protease inhibitors mimic the ..
the transition state conformation
Anti-thrombin (ATIII), what does it do and what happens if you don’t have this protein?
inhibitor protein that stops clotting by inactivating the serine proteases and thrombin
-without it you will have thrombosis (formation of too many clots which isnt good)
alpha 1 Anti-trypsin (AT-I), what does it do, without it what would happen?
- inhibits elastase in the lung
- without it you would have very little elastin in the lungs, causing emphysema like symptoms (ie. SOB)
Pancreatic Trypsin Inhibitor
Inactivates inappropriate activation of proteases in the pancreaas
T cell receptors that are MHC Restricted means
they have to interact with the right MHC molecule on the B cell and APC and the MHC has to have the antigen, and the TCR has to recognize both for T cell to activate
the complement receptors that aids in B cell binding to the Ag to find it is…
CD3 and CD19
transmembrane IgM and IgD to secreted IgM and IgD are made via which splicing..
RNA splicing
secreted IgG isotypes are made via which splicing..
DNA splicing
Both IgM, IgD, and IgG splicing are activated via
AID
Remember that cancer can be expressed when
-you have multiple genes (proto-oncogenes and tumor suppressors) mutated
CML is
is a proto-oncogene that is gives you leukemia when you have chromosomal translocation t(9:22)
Chromosome Breakage Syndromes
disorders associated with defect in DNA repair mechanisms or genomic instability, and patients with these disorders show increased predisposition to cancer.
ie. HNPCC (mismatch repair defect)
Protooncogenes
- genes that are involved with cell proliferation
- are dominantly acting
- result in leukemias and lymphomas
- mutations are usually translocations (chromosomal rearrangements), gene amplifications, and pt. mutations (less common)
- mutations are acquired
- usually becomes an oncogene due to gain and change of function
Tumor suppressor
- genes which are involved in cell growth control
- They are recessive acting
- mutations inherited
- mutations cause solid tumors
Types of Prenatal Testing, which one is ideal to do?
Non-invasive and Invasive. Preference is for non-invasive
Ultrasound (what is it, advantages and disadvantages, what do you find?)
- around 18 weeks gestation
- verifies viability, possible abnormalities and a variety of defects (ie. Down Syndrome, Clefting)
- Determines gestational age, and multiple pregnancies.
NIPS testing (what is it, advantages and disadvantages, what do you find?)
- uses cell free dna from maternal blood giving information of the fetus as well.
- isolated 10-22 weeks gestation
Two methods:
Counting method- detects aneuploidies (ie. trisomy) but can not differentiate between maternal and fetal abnormalities, and a vanishing twin.
SNP based NIPS- detects aneuploidies more accurately and can differentiate between mother and fetal abnormalities, and vanishing twin.
MSAFP testing
-non-invasive blood test
- gestational age of 15-20 weeks
- screening test for risk assessment of fetus
High levels- ONTD
Low levels- Down syndrome
-Disadvantages: less sensitive and does not predict outcome (remember just risk)
AFAFP testing (what is it, advantages and disadvantages, what do you find?)
- runs AFP on the amniotic fluid extracted from the amniocentesis procedure.
- low AFP levels (confirmed with Karyotype analysis and FISH) indicate risk of:
- trisomies 13, 18, and 21
- triploidy
- Mosaic turner syndrome
high AFP levels indicate:
open neural tube defects (ONTD) - is confirmed via acetylcholinesterase test.
Chorionic Villus Sampling (what is it, how many weeks gestation, advantages and disadvantages, what do you find?)
- Invasive
- 10-14 weeks gestation
- advantage: can be done earlier
- Disadvantage: higher risk of limb reduction if before 10 weeks and higher risk than amniocentesis of abortion 1/100
Amniocentesis (what is it, how many weeks gestation)
- Invasive
- 16-18 weeks gestation
- removes some aminotic fluid which contains some fetal cells which can be used to do multiple tests
disadvantages
-there is some risk 1/300 result in abortion
Mitochondrial diseases are inheritance patterns are
autosomal and x-linked mutations of nuclear genes or chromosome itself.
Forensic DNA analysis strategies
Mitochondrial DNA analysis and Nuclear DNA Analysis
Mitochondrial DNA analysis
-creates family identity linked through the mom and her siblings (which have the same mitochondria
Nuclear DNA analysis
(preferred for unique identification)
- Involves DNA Fingerprinting and micro satellite analysis
- used alot in criminical inclusions and exclusions of suspects, and paternity and testing
- differentiates between siblings
Personalized medicine
- genotype is found in the individual and used for preventative treatment before disease shows symptoms.
(ie. Angelina Jolie finding out she has BRCA mutation and cutting her breasts off as a result of that, prior to getting the disease..it helped her knowing)
PGD (Pre-implantation Genetic Diagnosis)
-screens the baby at the embryo stage, by removing the cell and undergoing FISH to see for abnormality
Next Generation Sequencing (Assisted Diagnostic Technology)
- used to sequence the whole genome of fetus
- will eventually replace PGD
Types of Screening testing in Pregnancy
Carrier, Newborn, and Prenatal Testing
Carrier Testing
risk assessment of being a carrier before the baby is born
Newborn Testing
-testing for disorder of the baby already born
Prenatal Testing
-testing for likelihood of disorder in the fetus
RSV (the basics)
- enveloped virus that infects infants at the respiratory epithelium, causing croup
- leaves the cell via budding
CMV
- virus cause Mono-like symptoms but different than EBV that it doesn’t produce sore throat
- can cause systemic disease in immunocompromised
- causes rash, jaundice, hepatosplenomalgy
What are the risk factors for Breast cancer?
- advanced age
- family history
- BRCA gene mutations
- Ethnicity (Ashkenazi Jewish ancestry)
- Increased life time estrogen exposure
For high risk patients to reduce breast cancer you would treat by… why?
- use breast cancer receptor modulators like Tamoxifen and Raloxifene
- reduces Estrogen Receptor (ER+) Breast cancer
Stage 0-
In situ (lobular or ductal) -Treated with tamoxifene and raloxifene (lobular)
-Breast conserving surgery and radiotherapy (ductal)
Stage 1 and 2
early invasive
-treated with breast conserving surgery +radiotherapy with systemic chemo
Stage 3
locally advanced
-Induction of chemotherapy to reduce the tumor size followed by surgery and radiation therapy
Stage 4
- Metastatic
- treated with just radiation therapy and systemic therapy
-23% chance of survival for 5 years with treatment
Luminal A and B tumors
- majority are ER+ HEr2- and have better prognosis. (70%)
- Luminal A has a better prognosis than B
Her2 tumors
- have a bad prognosis (ER-, Her2+)
Gene Expression Profiling techniques for Breast Cancer
Oncotype DX (RT -PCR of 21 genes)
and
Mammaprint (DNA microarray of Frozen tissue of 70 genes)
With the Oncotype DX Study results showed
basically the ODX results made no recommendation on chemotherapy recommendations
80 percent of breast cancers are … 20 percent are…
sporadic,… familial
HEr2
-is proto-oncogene that is a receptor tyrosine kinase.
It is converted to oncogene via gene amplification. (can be detected via FISH and CISH)
Her2 treatment
Herceptin - Trastuzumab (extracellular action)
Lepatinib (intracellular action)
Trastuzumab-DM1 -anti-microtubule chemotherapy
Maternal Serum Quad Test
- 10-13 weeks gestation
- 4 different substances (ie.HcG, AFP ) used to detect abnormalities (80 percent detection for risk of Down syndrome
To calculate the rate of the reaction (V) the equation is:
v= vmax*([S]/[S]+Km)
To calculate the Km the equation is:
=k2+k3/k1
=[S] at which you have reached 1/2 vmax
To calculate Vmax the equation is
k3(Et)
To calculate the fraction of ES at any concentration f[ES]
v/vmax
which equals
=[S]/[S]+km
To calculate kcat the equation is
vmax/Et
and
=k3
To measure the ki the equation is
(E)(I)/(EI)
In regard to an effective protease Inhibitor to work the best it must be able to fit into the protease active site by
matching substate transition state conformation and have low Ki
In micro-satellites, repetitive bands in cancer tissue resulting from Chromosome breakage syndromes such as (HNPCC) indicate
-errors (mutations) or defect in DNA Repair mechanism causing the number of repeats
what is the enzymatic equation for efficiency?
-kcat/km
- kcat describes how much ES is used
- km describes how much ES complex is available
For a HIV protease to be resistant to an inhibitor, you have to have a
-higher Ki than the wild-type and near in kcat/km than the wildtype
on the lineweaver-burk plot you have x intercept equal to
-1/km
on the lineweaver-burk plot you have y intercept equal to
1/vmax
on the lineweaver-burk plot you have slope equal to
Km/vmax
why do we do enzyme assays at saturating substrate?
at this point change in substrate concentration is linear with change in product and
also
velocity (vmax) would be directly proportional to enzyme concentration. (Vmax=Et)
