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111 Cards in this Set
- Front
- Back
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When introducing mutations via PCR, you want to use a DNA with _____ fidelity
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Low
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DNA Synthesis occurs in what direction?
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5' to 3'
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The template in DNA synthesis is read in what direction
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3' to 5'
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DNA Poly 1 has ____ functions. What are they?
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Two. One is DNA polymerization and the other is DNA degradation. When repairing nicks not only is the nick filled in but all nulcleotides after are removed and replaced.
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The klenow fragment is a type of ________. What activity does it lack?
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DNA polymerase, it lacks 5' to 3 exonucleoase activity (the degredation function)
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What kind of DNA polymerase lacks 3' to 5' exonuclease activity??
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Low Fidelity DNA Polymerase
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Name three random methods of mutagenesis
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Random mutation using nucleotide analogs
Error Prone PCR DNA Shuffling |
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What happens to Asparagine and Glutamine at high temperatures?
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They are deaminated and become Aspartic acid and Glutamic acid respectively. Aspartic acid reduces protein half-life
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Mutations can be either ____ or ______
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Spontaneous or induced
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What did Hermann Muller discover?
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That external agents can increase mutation rates.
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What are the five chemical actions of mutagens
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Base analogs
Hydroxylation Deamination alkylation Intercalation |
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5-Bromouracil acts like this base normally, but can rarely act as another base as well. Name the two bases
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Thymine, Cytosine
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Hydroxlamine is what kind of mutagen?
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Hydroxylating agent
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Cytosine, if hydroxylated, acts like what base?
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Thymine
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Ethylmethane sulfonate is what type of mutagenic agent? And what bases does it act on?
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An alkylating agent, acts on guanine or thymine.
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If alkylated, guanine acts as which base?
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Adenine
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Nitrous acid is a _____ agent
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Deaminating
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Cytosine, if deaminated, acts as which base?
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Uracil
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Intercalating agents cause which type of mutation?
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Frameshift
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Name 5 types of DNA damage
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Depurination
Deamination Double strand break Thymine dimerization Oxidation |
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Which two bases are purines? Pyrimidines?
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Purines: Adenine and Guanine
Pyrimidines: Thymine and Cytosine |
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True or False: UV rays can cause cause double strand breaks.
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False. You need X-rays/gamma rays/alpha particles.
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Imatinib/Gleevec's target
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Bcr-Abl
PDGFR, Kit |
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Gefitinib/Iressa's target
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EGFR (Epidermal Growth Factor Receptor)
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Cetuximab/Erbitux's target
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EGFR
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What does "inib" indicate if it's at the end of a drug's name?
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It means the drug is a small molecule kinase inhibitor.
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What does "mab" indicate if it's at the end of a drug's name?
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It means the drug is a monoclonal antibody, a large molecule.
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Bevacizumab/Avastatin's target
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VEGF
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Trastuzumab/Herceptin's target
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Erb2
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Name six 2nd messengers
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cAMP
cGMP DAG IP3 Ca++ Inositol Phospholipids |
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What enzymes add and remove phosphate groups?
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Kinase adds it, phosphatase removes it.
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What's the largest group of cell surface receptors?
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G-Protein receptors
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The g protein directly controls what?
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An effector protein
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What are GPCR's downstream pathways?
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cAMP/IP3 2nd messenger pathways
MAP Kinase Linked ion channels |
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Cytokine receptors have how many TM domains?
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Just 1 but there's 2 receptors that bind 1 ligand
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The cytosolic side of cytokine receptors is associated with what?
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JAK Kinase
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JAK Kinase activates what downstream signal?
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STAT transcription factors
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How is JAK activated?
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By adding phosphate to lip tyr.
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What are some ligands that can bind to cytokine receptors?
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Epo, IFN, Interleukins
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What does the SH2 site of STAT recognize?
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Phosphorylated Tyr
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How is STAT's NLS (nuclear localization signal) opened?
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It opens when STAT dimerizes.
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What are some Recepetor Tyrosine Kinase (RTK) ligands?
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Insulin
EGF - Epidermal GF FGF - Fibroblast GF VEGF - Vascular Endothelial GF (Bevacizumab's target) |
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TK has what downstream signal transduction pathways?
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PI3
IP3 RAS-MAP kinase |
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How are cytokine receptors and RTK similar?
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Both single TM, have 2 receptors that dimerize to bring together intracellular domains that are phosphorylated.
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TGF-B ligands?
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Transforming Growth Factor-B family
Activin Inhibins |
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Which receptor activates Smad?
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TGF-B
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TGF uses what kind of kinase?
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Serine-threonine
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What aspects of TGF-B receptors set it apart from RTK and Cytokine receptors?
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It uses 3 transmembrane receptors not 2 and uses Serine-Threonine kinase rather than Tyr-kinase
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T/F: Hedgehog has 2 receptors?
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True
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Hedgehog's ligands?
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Sonic Hedgehog tethered to cell
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What are hedgehog's 2 receptors and how large are they?
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Patched (Ptc) is 12 TM
Smooth (Smo) is 7 TM |
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T/F: Ci acts as a nuclear activator.
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True
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The hedgehog pathway is most active when?
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During embryonic development.
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Phase II trial drugs that target the hedgehog receptor pathway are trying to treat what diseases?
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Basal cell carcinoma, ovarian cancer, metastatic colorectal cancer.
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Wnt's ligands
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Wnt or Wg (Wnt in mammals or wingless in drosophilla)
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When is the wnt pathway most active?
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In early life
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Wnt has has how many TM domains?
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7
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When the wnt receptor is activated, what happens?
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The proteosomal degredation of B-catenin is inhibited so it can activate a transcription factor
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How are hh and wnt receptors similar?
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They both have a molecule that is constantly degraded, suppressing gene expression.
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Describe what happens after wnt binds to its receptor.
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Wnt binds to LRP and frizzled (Frz).
Dishevelled is activated, lifting the GSK3/APC/Axin complex from B-catenin. B-catenin binds to and activates a transcription factor in the nucleus. |
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What are the notch receptor's ligands?
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Delta or serate, tm proteins on another cell.
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What are the extracellular and intracellular components of the notch receptor?
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The extracellular notch receptor and a noncovalently bound cytosolic subunit.
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Notch signaling is a good target for _______?
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Stem cells.
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Ob (Obesity) gene's product
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Leptin
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Db (Diabetes) gene's product
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Leptin Receptor
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What cell produces leptin?
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Adipocytes
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Mice deficent in leptin and leptin receptor have what type of gene mutation?
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Homozygous recessive
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T/F: Lowered levels of leptin signal hunger and suppress energy expendture.
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True
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Does leptin therapy in human's work in combating obesity? Why or why not?
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It does not work because most obese humans already have elevated levels of leptin. They lack leptin receptors
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Three possible reasons for obesity involving leptin
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1. Not making leptin
2. Not enough leptin for a given fat mass 3. Leptin insensitivity at site of action (hypothalamus mainly |
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What are 2 mechanisms of leptin resistance?
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1. Somehow leptin can't make it to the brain where it exerts its energy balancing effects.
2. Leptin receptor is mutated so it doesn't work properly. |
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What signal pathway does leptin use?
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JAK-Stat (also used in Cytokine receptors)
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The shorter forms of leptin receptor have what function?
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They transport leptin from the blood to the brain.
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When leptin binds to receptors in the hypothalamus, what molecules are secreted and blocked?
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Neuropeptide Y is inhibited
Norepinephrine is secreted |
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What does NPY do?
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Increases feeding
Suppresses energy expenditure |
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What Integrates feeding, thermogenesis, and energy metabolism?
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Neuropeptide Y
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What is PYY and what does it do?
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A peptide of the Y family released post-prandially from the intestines. It signals satiety
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Peripheral administration of PYY produces what effect? How does it compare to peripheral leptin administration?
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It decreases one's appetite. Leptin didn't have this effect. PYY injection into brain also had this effect
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T/F: Insulin stimulates fat production in adipocytes if there is too much glucose?
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True
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What type of receptor does insulin use?
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Receptor Tyrosine Kinase
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GIP signals _____ in response to ______?
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insulin release, nutrients
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Name 2 incretins?
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Gastric Inhibitory Protein (GIP), Glycogen Like Peptide-1 (GLP-1)
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GLP-1 signals what?
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Satiety and inslulin secretion
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CCK is released from ______ in response to ______
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duodenum, luminal nutrients (kinda like GIP)
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CCK regulates ________
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meal size
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Ghrelin signals ______
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hunger
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Apolipoprotein IV responds specifically to _______ and signals _______.
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Fat, satiety
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If you continually eat high fat meals, what happens to A-IV response?
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It suppresses A-IV's gene expression. The intestine will make it less and the hypothalamus will respond to it less.
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Is IFN-A a glycoprotein?
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Mostly no. All the other Human IFN are though.
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IFN-E appears to play a role where?
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In reproductive function and mammalian placentas.
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Which is the only Type II human interferon?
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IFN-Gamma
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What are the 2 common viruses used to induce IFN-A production in human lymphocytes?
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Sendai and Newcastle disease viruses
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In producing IFN-Gamma what cells are used?
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T-lymphocytes preferably
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One known signal transduction pathway for IFN Gamma uses ________
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JAK-STAT signal transduction
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T/F: Both Th1 and Th2 cells express gamma-R1 and R2 receptors?
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False, only Th2 cells have the gamma-R2 receptor. Both cell types have Gamma-R1
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T/F: Anti-viral activity is IFN-Gamma's primary role.
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False, it's primary role is more of an immune system modulating one. It communicates with T cells, B cells, and can stimulate cytotoxic activity.
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Name some diseases IFN-A can treat.
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Hairy Cell Carcinoma (IFN-A's 1st use)
Kaposi's Sarcoma Chronic Mylogenous Leukemia Chronic Hepatitis B and C (major use) HPV |
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How many R groups are there on Vitamin E?
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Three
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Which form of tocopherol is most abundant in our diet ?
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Gamma
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Which form of tocopherol is most affect reproductive function?
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alpha
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Folic acid is involved in what biochemical process?
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1 Carbon metabolism
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What is the RDA of folic acid for pregnant women?
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400 ug
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What dietary reference intake is most commonly used?
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RDA (Recommended Daily Allowance
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The AI level is usualy close to the ______
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RDA
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On a bell curve where does the EAR, RDA, AI, and UL fall?
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EAR is at the middle of the curve. RDA is 2 standard deviations from the EAR. AI is close to RDA but farther right. UL is very far off to the right.
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BMI takes what two body measurements into account?
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Height and Weight
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What populations are at a greater risk for diabetes?
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Asians, Hispanics, and Africans
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What popular weight loss suppliment was banned by the FDA in 2004?
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Ephedra
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Energy expenditure includes....
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Resting Metabolic Rate (1Kcal/min), Thermogenesis (10% of ingested food), Physical activity (4 kcal/min walkin, 12 kcal/min running)
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High glycemic load foods cause a slow or rapid rise in blood insulin levels?
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Rapid rise followed by rapid fall.
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The AICR says we should eat less ______ and more ______
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less red/processed meat, more plants
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