HB1-exam 1 note cards.txt

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HB1-exam 1 note cards.txt
2010-09-06 10:46:59
hb1 exam1

exam 1 hb1, general notecards
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  1. proteolytic cleavage
    done by proteases, example: removal of methionine after translation
  2. Zymogens
    inactive precursors that are activated by proteolytic cleavage, ex. clotting cascade (serine proteases cleave inactive zymogens)
  3. Clotting cascade (main point)
    To stimulate a thrombin burst-->convert fibrinogen to fibrin-->fibrin cross linkages create clot
  4. Acylation
    When a methionine is removed it is replaced by an acetyl group at the N-terminus (donated by acetyl CoA)
  5. Mryristylation
    Lipid anchors. Myristyl anchors embed themselves in the lipid bilayer; allows a protein that would normally not associate with the lipid bilayer to be attracted to that area
  6. Prenylation
    Prenylation attaches the cysteine residue and prenyl (15 residue farnesyl) group via a thioester. Fti inhibitors for Progeria try to block prenylation.
  7. Example of prenylation
    Prenylation is known to occur on proteins of the RAB family of RAS-related G-proteins, oncogenic GTP-binding and hydrolyzing protein RAS which is farnesylated
  8. DNA methylation
    Adding methyl group at CPG islands to DNA causes steric hinderance -->allows for transcription factors to bind-->STOP TRANSCRIPTION
  9. Histone acetylation
    When you acetylate histones (using HATS)->shields their charge->decreases their affinity for DNA->activate them-> ENHANCE TRANSCRIPTION, to deactylate use HDACs
  10. Histone methylation
    When histones are methylated, histones are deacetylated, DNA is methylated--> allows binding of transcription factors on outer DNA helix gene silencing (NO TRANSCRIPTION)!
  11. Phosphorylation
    Most common post translational modification, proteins are phosphorylated by kinases, AAs that are phosphorylatable are serine, threonine, tyrosine
  12. Physiological Example of Phosphorylation
    Phosphorylations that occur in glycogen synthase and glycogen phosphorylase in hepatocytes in response to glucagon release from the pancreas
  13. Ubiquitination
    ATP-dependent process that is major mechanisms for the destruction of cellular proteins, involves a complex structure referred to as the proteosome, ubiquitin carrier protein attaches ubiquitin to the protein with ubiquitin ligase
  14. Lactose
    glucose-galactose cleaved by lactase (non-inducible, brush border disaccharidase), rate limiting step in its digestioon is its hydrolysis not the transport of glucose and galactose
  15. Glycogen
    glucose molecules linked by alpha-1,4 glycosidic bonds (amylose), digestion promoted by amylase
  16. Primary monosaccharides
    glucose, fructose, galactose
  17. Glucose
    monosaccharide Na+ dependent glucose transported across brush border from mucosa-->enterocyte
  18. Galactose
    monosaccharide Na+ dependent transported across brush border from mucosa-->enterocyte
  19. Fructose
    monosaccharide Na+ independent facilitated diffusion (uses GLUT5) transported across brush border membrane from mucosa-->enterocyte
  20. Glycoprotein
    proteins with sugars covalently linked to their AAs, MOST CELL SURFACE MEMBRANES, usually contain amino sugars (N-Acetylglucosamine, N-acetylgalactoseamine), neutral sugars (D-galactose, D-mannose, L-fucose) or acidic sugars (sialic acid)
  21. Functions of Glycoprotein
    Hormone receptors at the cell surface, cell-cell interaction
  22. Proteoglycan
    long unbranched sugar chains, hallmark of disaccharide repeats, MOST ER and Golgi membrane proteins
  23. Functions of Proteoglycans
    Many of ER and Golgi membrane proteins, also proteins secreted from the cell like serum and mucus proteins, Glycosylation is the major enzymatic modification in the body
  24. N-linked proteins
    N-glycosidically linked oligosaccharides widespread in nature, characteristic of membrane and secretory proteins, linked by N-acetylglucosamine (GlcNAc)--connected to asparagine
  25. O-linked proteins
    O-linked found in mucous fluids, but can also be present in membrane and secretory proteins, 3 or more sugars linked by N-acetylglalactosamine (GalNAc)--connected to serine, theronine. O-linked found a lot in collagen
  26. Collagen Synthesis
    First procollagen (N-linked glycoprotein)-->N linke oligosaccharide is removed ("N")-->only O linked remain in mature collagen
  27. Collagen glycosylation
    Degree of glycosylation impacts structure--> less glycosylated collagen=ordered fibrous structure (tendons) while heavily glycosylated are more like meshwork structure in basement membrane
  28. N-linked protein in hormones
    GlcNAc is linked to serine residue that become phosphorylated by protein kinases in hormonal stimulation
  29. High mannose N-linked protein
    all N-linked glycoproteins have oligosaccharide chains coming off a common core 3 mannose residues+2 GlcNAc, high mannose is how they all start some glycoproteins are modified further after this
  30. Tetra-antennary type N-linked protein
    Complex chains which have terminal trisaccharide sequence of sialic acid0galactose-GlcNAc attached to branched core mannoses
  31. LDL receptor glycoprotein structure
    has 2 N-linked oligosaccharides near LDL-binding domain (not involved in binding) and cluster of O-linked oligosaccharides near membrane spanning region (sialic acid residues to hold it up)
  32. Biosynthesis of N-linked glycoproteins
    Synthesized in the ER. Dolihcol is the anchor in the lipid bilayer of the ER membrane-->first sugar is GlcNAc-1-P-->another GlcNAc-1-P --> 4 or 5 mannose residues--> 3 glucose residues (which are later removed) NEXT STEP modificaton in the ER-->sent to Golgi-->elongation
  33. Biosynthesis of O-linked glycoproteins
    Occurs in the Golgi occurs in stepwise fashion of addition of sugars
  34. High mannose oligosaccharides in Lysosomes
    Lysosomal enzymes are N-linked oligosaccharides are synthesized in the ER and Golgi
  35. Lapatinib (HERCEPTIN)
    Small molecule drug to treat HER2 resistant breast cancer by bind to ATP recptors-->Blocks the tyrosine kinase from binding
  36. Imatinib
    Small molecule drug to treat CML by bind to ATP recptors-->Blocks the tyrosine kinase from binding
  37. Proteoglycans
    Gel forming compounds made of protein backbone with covalently bound sugars, oligosaccharide chains have disaccharides repeats usually composed of amino sugar and uronic acid
  38. Glycosaminoglycans (GAGs)
    the carbohydrate part of proteoglycans, each has unique disaccharide repeat, usually includes hexosamine and uronic acid (EXCEPT FOR KERATAN SULFATE), amino sugars are usually glucosamine (GlcNH2) or galctosamine (GalNH2) present in their N-acetylated form
  39. Hyaluronic acid
    proteoglycan, no sulfation--located in joint and ocular fluids
  40. Chondroitin sulfates
    proteoglycan, located in cartilage, tendons, bone
  41. Dermatan sulfate
    proteoglycan, located in skin, valves, blood vessels
  42. Heparan sulfate
    proteoglycan, amino group sulfated (not acetylated) located in cell surfaces
  43. Heparin
    proteoglycan, amino group sulfated (not acetylated) located in mast cells and liver
  44. Keratan sulfate
    proteoglycan, uronic acid replaced by galactose, located in cartilage, cornea
  45. Synthesis of proteoglycans
    synthesized by a series of glycosyl transferases, epimerases, sulfo transferases. Synthesis of core oligosaccharide while still in the RER, then synthesis of the repeating oligosccahride and other modifications take place in the Golgi
  46. Germline mosaicism
    X-inactivation causes one X chromosome to be inactivated in some tissues and the other X chromosome to active in others
  47. X-linked mental retardation
    X chromosome has a high frequency of mutations, microdeletions, duplication that cause X linked mental retardation
  48. LDL receptor
    defects in this receptor are responsible for familial hypercholesterolemia (autosomeal dominant) it's a transmembrane glycoprotein!
  49. factor VIII
    Allel coding for this causes hemophilia A--X-linked recessive, usually seen in males not females
  50. X-linked recessive (can females ever have phenotype)?
    If the father is a carrier on his X and the mother is a carrier then female offspring would be homozygous affected (rare because of the low incidence of X-linked recessive disorders)
  51. Skewed X-inactivation
    X inactivation (usually random) the fraction of mutant alleles that remain active is much greater than normal, the deleterious allele finds itself located on active X, if this is present in pertinent tissues then you will have disease
  52. Unstable repeat expansions
    Genetic diseases caused by the expansion within an affected gene of DNA with repeating units of three or more nucleotides in tandem (CAG or CCG)-->primarily neurological conditions result
  53. Unstable repeat expansion diseases
    Myotonic dystrophy, fragile X syndrome, Huntington's Disease (polyglutamine disoder), spinocerebellar ataxias (polyglutamine disoder)
  54. Anticipation
    Genetic term referrring to the progressive severity and decrease in the age of onset for diseases that are passed through the pedigree
  55. Disease associated with Anticipation
    Fragile X, Myotonic Dystrophy, Huntington's
  56. Huntington's disease
    CAG repeats
  57. Spinocerebellar ataxia
    CAG repeats
  58. Fragile X
    CGG repeats
  59. Myotonic Dystrophy
    CTG repeats
  60. Fatty acid synthesis
    Step 1: turn acetyl CoA--> malonyl CoA (using Biotin and acetyl CoA carboxylase), Step 2: elongation of fatty acid chain in two
  61. Phospholipid synthesis
    occurs on the cytoplasmic face of the ER, uses CDP-->CMP and flippases who flip the phospholipid one leaflet of the bilayer to the other
  62. Cholestrol
    Phospholipid, has a polar head group and a largely non-polar hydrocarbon tail. When it enters the bilayer, it causes stiffening. It will sit in hydrophobic tail region. It exists at quite a high level at the bilayer. By stiffening the bilayer, you alter the properties, even changing membrane permeability.
  63. Fluid mosaic model
    Singer, Nicholson said that the phospholipid bilayer has assymetry that is caused by differential packing of p-serine vs. p-choline
  64. Phospholipids in the bilyaer
    phosphotidyl serin phosphotidyl choline
  65. lipid rafs
    another example of asymmetry--mobile--float around bilayer, environment inside rafts is different from outside- Caveoli
  66. Dominant negative effect
    Mutation in gene regulatory region, If you get a mutation in the regulatory region it has an enhanced effec as a result of kinase activity
  67. Dominant negative effect (disease example)
    Amylotrphic lateral sclerosis, causes proteins to aggregate and interfere with cellular function
  68. PDZ Domain
    scaffold protein to bind ion channels to membrane, 80-90 AAs 6 strand Beta sandwich flanked by alpha helices, recognizes the C-terminus of receptors, involved in anchoring the CFTR in lung epithelial cells
  69. SALT BRIDGE in Hb
    ionic bond between lysine and glutamate
  70. Hemoglobin
    Oxygen carrier, iron in heaxcoordinate (binds 4 porphyrin, 1 proximal histidine, 1 oxygen) porphyrin ring is tetra coordinate
  71. Cooperativity
    When the binding of one oxygen molecule increases the binding affinity of the other sites, tense (low affinity), relaxed (high affinity)
  72. Allosterism:
    when the binding of one molecule at a site other than the active site increases or decreases the finction there
  73. Bonding between base pairs in DNA
    Hydrogen bonding
  74. Alpha helix (macrodipole)
    N terminus is positive, C terminus is negative
  75. Hydrophobic interactions
    Ex. oil in water-->increase entropy of system by liberating water molecules, all aromatice molecules are nonpolar (hydrophobic)
  76. Sterochemistry of enantiomers
    Animals are almost exclusively L-amino acids, sugars are all D-sugars
  77. # exons in B-globin gene
  78. # exons in BRCA1
  79. # exons in B-myosin heavy chain (MYH7)
  80. Prokaryotic vs. Eukaryotic DNA
    Prokaryotic Genes On, Eukaryotic OFF, Prokaryotic no DNA-protein complexes, Eukaryotic has DNA-protein complexes
  81. Stop codons
    UGA, UAA, UAG (you go away, you are away, you are gone)
  82. Kozak sequence
    Sequnce that the AUG start codon in included within (in the 5'UTR region)
  83. Exon-Intron splice
    GT (3' end of exon, 5'end of intron)----->AG(5' end of exon, 3'end of intron)
  84. Transcription factors
    TATA box (complimented by iniator), CAAT box, GC rich
  85. Large genes (>100bp)
    Factor VIII, CFTR, Dystrophin, BRCA1
  86. Small genes (<10 kb)
    B-globin, insulin
  87. Medium gene (10-100bp)
    collagen, LDL receptor
  88. Avergae number of exons per gene
    10 exons
  89. Pseudogene
    transcribed but not translated or not transcribed at all--can lead to unequal crossing over
  90. Unequal crossing over
    misalignment of two alpha globin genes on a chromsome causes alpha-thalassemia
  91. tandem repeats
    Repetitive DNA sequences-satellite DNA near centromeres
  92. SINEs
    short interspersed nucleotide repeats (10% human DNA), can interfere with crossing over, ex. Alu repeats SINEs cause familial hypercholesterolemia
  93. Which exon is lost in the unequal crossing over Familial Hypsercholesterolemia
    exon 5
  94. LINEs
    long interspersed nucleotide repeats (20% human DNA), can be transposable elements
  95. Mitochondrial DNA
    37 genes, amternal inheritance, no introns, highly conserved, makes more mutations, 2 strands heavy-guanine rich and light-cytosine rich
  96. Heteroplasmy
    the mixed population or normal and mutant mtDNA
  97. Types of DNA
  98. Z DNA
    left handed turn
  99. Histones (#)
    two copites of each of the four core histone (H2A, H2B, H3, H4)
  100. Histones that can substituted
    H3 and H2A
  101. Histones that can be chemically modified
    H3 and H4
  102. Histone code
    the pattern of major and specialized histone types and their modifications
  103. Cell division
    4-6 hours to reproduce 6.4 Gb
  104. High fidelity
    DNAs ability to reliably replicate
  105. DNA error rate
    1 in 10^9 is the limit, actual rate is 1 in 10^6 it fixes it by proofreading!
  106. DNA licensing
    ensure that DNA replication is limited to once/cycle
  107. Replication origin
    replication origins are rich in A-T (easier to break)
  108. Number of replication sites (Prokaryotic vs. Eukaryotic)
    E. coli have 1, humans have 100,000
  109. Steps of DNA Replication
    1. unwinding & replication forks, 2. stabilization with SSBPs, 3. Iniation (priming with DNA polymerase alpha), 4. Elongation (5'-->3'), 5. Lagging strand synthesis (3'-->5'' semgents) discontinuous, 6. Licensing: ensuring each replicates only once/cell cycle
  110. Helicase
    DNA strands are separated in ATP-dependent fashion
  111. Topoisomerase
    prevent DNA from becoming supercoiled
  112. Single stranded binding protein
    stabilize leading strand
  113. DNA Polymerase
    Can only add to the 3' end nucleotides, needs Magnesium to function
  114. DNA Pol alpha
    AKA RNA primase, synthesizes an RNA primer and then acts as a DNA pol to elongate for about 20 bp
  115. DNA Pol delta
    Lagging strand synthesis, Highly processive, proofreading 3'-->5'
  116. DNA Pol E
    Leading strand synthesis, Highly processive, proofreading 3'-->5'
  117. Processivity
    stays on strand longer
  118. PCNA (clamps)
    ATP-dependent way to increase the processivity of the Polymerase (stay on the strand)
  119. Prokaryotic Polymerazes
    DNA Pol 1, II, III
  120. Main polymerase in bacteria
    DNA Pol III
  121. RNAase H
    takes off the small RNA primer and DNA pol delta and epsilon fill it in
  122. Semi-discontinuous synthesis
    Lagging strand is built in segments (Okazaki fragments)
  123. Okazaki fragments
    segments of DNA on the lagging strand
  124. DNA Ligase
    glues together Okazaki fragments
  125. Replisome
    the whole complex of helicase, SSBPs, Polymerase, PCNAs
  126. Replication
    4-6 hours for 6.4 Gb, 100,000 replicons, during S phase
  127. CDC 6
    CDC6 recruited to form pre-replication complex, licensing to ensure 1 DNA replication/cell cycle, by the end of G2 there is no CDC6 left
  128. Type of DNA Damage
    Spontaneous, Exogenous (UV, Radiation, Chemical)
  129. Spontaneous DNA damage
    Deamination (standard bases are exchanged for nonstandard bases), base loss (Depurination>depyrimidation), ROS
  130. Ionizing radiation
    Causes double strand breaks by hydrolysis of water which breaks down into ROS
  131. UV Radiation
    Photo activate nucleotides, causes thymine (pyrimidine) dimer formations
  132. Adduct formation
    covalent attachment to DNA nucleotides, ex. benzo[a]pyrene
  133. Alkylating agents
    Carbn comound group to one of the bases-->disrupts structures, Ex. CYTOXAN
  134. Crosslinking
    Bi functional-->2 adduct forming entities can bond two 2 positions on DNA (can be inter or intra strand), Ex. CISPLATIN
  135. Type II topoisomerase inhibitor
  136. Microsatelitte Instability
    Occurs during replication of repetitive sequences, Forward slippage (parent) causes deletion, backwards slippage (daughter) causes insertion
  137. Translesion synthesis
    DNA backbone is still intact but you will get replication error
  138. DNA Double strand break
    caused by ionizing radiation, most deleterious form of DNA damage-->leads to aneuploidy
  139. Cell cycle checkpoint
    Eukaryotes have cell cycle checkpoints at G1 and G2, focus on checkpoint for G2--if you have mutations in the genes that code for checkpoints
  140. Why use alkylating agents, crosslinking agents in cancer therapy?
    Tumor cells grow faster than normal counterparts, should be more susceptible to checkpoint
  141. DNA Repai pathways
    Base Excision repait, Nucleotide Excision Repair, Translesion Synthesis, Mismatch Repair, Homologous Recombination, End joining
  142. Base Excision Repair
    Deaminations, depurinations-->uses glycosylases to cut out damaged base (least flexible)
  143. Nucleotide Excision Repair
    UV photoproducts, cross links-->RNA pol encounters DNA lesion, stops, uses a multiprotein complex (>10 proteins) for primary repair mechansim of UV photoproducts, cuts 5 bases 3' of the damage and 23 bases 5' of the damage, gaps filled by DNA pol
  144. Mismatch Repair
    Replication error (ex. Lynch Syndrome)
  145. Homologous recombination
    Double strand break, adducts, cross links
  146. End joining
    Double strand breaks
  147. Translesion synthesis
    Not high fideltity, can pass by damage, very error prone, non-templated manner
  148. XPA and XPC addount for (%) of all XP cases
  149. How to test for XP?
    Unscheduled DNA synthesis with skin biopsy (use radiolabeled thymine)
  150. Where is rRNA synthesized?
  151. Where does capping and polyA tail are added after transcription, where?
  152. Transcriptional unit
    TATA, GC, CAAT box, Enhacers and Silencers (on the DNA), TFIID
  153. Transcription Termination sequence
  154. RNA Polymerases
  155. What causes mushroom poisoning?
    alpha-Amanitin, is a mushroom poisoning RNA pol II inhibitor-->block mRNA transcription
  156. RNA polymerases
    Enzymes that synthesize the RNA strand from a DNA template during transcription
  157. RNA pol II transcribes which RNA?
  158. mRNA is transcribed using what RNA Polymerase?
    RNA Pol II
  159. RNA pol II transcribes which RNA?
    mRNA and microRNA
  160. RNA pol III transcribes which RNA?
    tRNA and ribozymes
  161. Stages of transcription
    1. initiation (construction of RNApol complex on the promoter, recruitment of transcription factors), 2. Elongation, 3. Termination (cessation of RNA transcription with CG repeats)
  162. Does RNA Polymerase has its own helicase activity?
  163. TATA Box
    10-20% of human promoters, 25-30 bases upstream of trranscription start site, allows correct positionaing of RNA pol
  164. TBP
    TATA binding protein, first to bind the DNA, causes the DNA to bend-->recruits TFIID and other transcriiption factors
  165. General transcription factors (GTFs)
    required for PolII in a test tue are TFIIA, B,D, E, F, and H (but basal level is achieved with purified B and F)
  166. Elongation
    RNA pol requires energy to add ribonucleotise to the 3' end of the growing strand, 17 bp transcription complex with 8 bp DNA-RNA hybrid
  167. Abortive transcription
    RNApol shows strong binding to promoter and generates short 9bp RNA fragments-->eventually it clears the promoter
  168. Rho factor (prokaryotic)
    Termination factor dependent for termination, used in bacteria
  169. How is transcription different in prokaryotes
    RNA pol directly recognizes sequences in DNS for binding and transcription, no nuclear envelope, no introns, transcription/translation occur simultaneously, use of polycystronic messages (like the LAC operon)
  170. Antibiotic that target prokaryotic transcription
    Rifampin binds to beta subunit of prokaryotic RNApoly, Dactinomycin (actinomysin D) binds to DNA template and interferes with RNApol progression
  171. Reverse Transcription
    Viral RNA used reverse transcriptase. Take mRNA strand and reverses transcription to turn it into DNA. Then it inserts itself into our genome
  172. Gene Regulatory Proteins
    Helix turn helix, zinc finger, leucine zipper, winged helix, winged helix turn helix, helix loop helix
  173. Helixa turn helix
    Repressor protein
  174. Zinc Finger
    Zn ion to stabilize structure/finger/specific triplet of base pairs, Zn ion causes secondary structure, bind major groove
  175. Leucine zipper
    Leucine every 7th residue, "zips" up to dimerize the protein, needs a dimer to inhibit DNA
  176. Winged Helix
    4 helices and two strand beta sheet
  177. Winged helix turn helix:
    3 helical bundle and 4-strand beta sheet
  178. Methylate histone
    Block charge-->activate transcription
  179. Acetylates histone
    Block charge-->activate transcription
  180. Methylate DNA
    Methylate DNA at the CpG island-->inhibit transcription
  181. Nucleosome
    Histone complex (8 total) with the DNA wrapped around it
  182. Histone acetyltransferases (HATS)
    Acetylate histones
  183. DNA Binding Proteins (enhancer/silencers)
    Regions that can contain multiple elements for assemply of large protein complexes--can be 1000s of bps away
  184. Multi-domain proteins
    activators and repressors can have multiple functions besides serving as transcriptional regulators
  185. Polycystronic message
    message with a length of RNA with whole process associated through several consecutive genes--all related to same process
  186. Lac Operon
    B-galactosidase cleaves lactose into allolactose-->bind repressor subunits to prevent assembly-->cAMP starvation signal forms CAP cAMP and promotes RNA pol attachment--> RNA pol transcribes genes to produce B-Galactosidase, permease and acetylase
  187. Halflife of RNA
    10 hours
  188. Chronic Myeloid Leukemia
    15-20% of all adult leukemias, BCR-ABL-->ABL (tyrosine kinase) --> speeds up cell division and inhibits DNA repair
  189. Regulation of RNA turnover- AUUUA sequences
    Experiment deomstrating the destabilizing effect of AUUUA sequences-->shortened the halflife of B-globin mRNA from 10h-->1.5h
  190. Nonsense Mutation
    is when you get a stop codon before you should
  191. Nonsense mediated decay
    Inserting stop codon where they shouldn't be
  192. Regulation of RNA turnover-- IRE-bps
    In high iron, the mRNA that codes for transferrin is off. When you have low iron, you want to pump the iron in so the IREbps stabilize the stem loops and turn the transferrin on-->you get lots of transferrin and protect your little iron
  193. What exon is removed through alternative splicing in CF?
    exon 9
  194. RNA splicing-Lariat
    Just 5' of acceptor site is pyrimidine rich acceptorregion that forms lariat site, branch site a single A binding is sitting just upstream of the pyrimidine rich region and is where the lariat lands
  195. What is the reason for alternate splicing?
    The human genome is limited
  196. Alternate RNA Splicing include or exclude certain exons?
    Ex. alpha-tropomyosin, alpha-TM Exon Gene organization uses alternate splicing to produced different types of muscles fibers
  197. Exonic splicing enhancers (ESEs)
    Enhance recognition of splice site- can bind directly or indirectly
  198. Intronic splicing enhancers (ISEs)
    Enhance recognition of splice site- can bind directly or indirectly
  199. Exonic splicing silencers (ESSs)
    Silence recognition of splice site- can bind directly or indirectly
  200. Intronic splicing silencers (ISSs)
    Silence recognition of splice site- can bind directly or indirectly
  201. Cryptic splice site
    splice site that is not supposed to be there, causes competition between splice sites
  202. Gain of function mutation
    Creation of cryptic splice site
  203. Loss of function mutation
    A splice site is weakened or destroyed
  204. In CF, regulation of splice site
    A splice site in intron 8 regulates inclusion of exon 9, in CF you don't get exon 9 included
  205. CF compound heterozygote, R117H and 7T
    mild presentation of disease, congentical bilateral absence of vas deferans
  206. CF compound heterozygote, R117H and 5T
    mild CF, disease symptoms present
  207. deltaF508
    most severe mutation that is associated with CF
  208. MAPT
    codes for tau protein, chromosome 17, involved splicing for exon 2, 3, 10 mutations can disrupt the balance of isoforms and cause disease--> ALZHEIMERS
  209. miRNA synthesis
    Synthesized in the nucleus as double stranded RNA, forms hair pin loops in nucleus, Drosha suts the hair pin loops in the nucleus, Exportin 5 sends it out to the cytoplasm where Dicer cuts it into 20-30 bp fragments, transciptional cleavage, now the miRNA can recognize its homologous RNA on the RISC complex
  210. Drosha
    cuts the hairpin loops of Pri miRNA in the nucleus to turn it Pre-miRNA
  211. Exportin 5
    Exports Pre-miRNA into the cytoplasm
  212. Dicer
    chops up the Pre miRNA into 20-30 bp fragments
  213. RISC
    complex that the anti sense strand binds to-->blocks translation
  214. Epigenetic
    study of heritables changes in gene function that occur without a change in the sequence of DNA
  215. CpG island
    C and G rich area in the 5' regulatory region close to the promoter region of DNA that gets methylated-- YOU METHYLATE THE C (cytosine)
  216. Location of LncRNAs
    Located in the nucleus and then trafficked to the cytoplasm
  217. Heterochromatin
    Highly compacted DNase resistant DNA
  218. When you acetylate histones which residue do you tag?
  219. When you methylate the histone, which residue do you tag?
    Cytosine (the C's of the CpG islands)
  220. Can drugs demethylate DNA?
    yes-through drug reversal you can restore transcription
  221. Rett Syndrome
    MECP2--Methyl CpG binding protein--no males can have Rett Syndrome unless they have Klinefelters (XXY) because if you have only on mutant X you won't have any normal protein
  222. What gets ADP ribosylated in Cholera?
    G protein
  223. Sumoylation, Small Ubiquitin like Modifier (SUMO)
    ADP ribosylation
  224. What genetic condition are likely to have epigenetic component?
    Imprinted genes--prader willie and angelman (7 genes missing on chromosome 15, in normal the maternal allele is expressed, paternal allele is silenced-when the maternal allel is lost you get Angelman)
  225. Example of secondar structure of RNA
    Stem-loop and small subunit of rRNA
  226. rRNA
    structural RNA (80% of all processed DNA)
  227. tRNA is the only RNA with non standard bases, what are they?
    Inosine and pseudouridine
  228. Are tRNA's aminoacylated?
    Yes, it uses ATP to give a high energy bond to the AA which is transferred to the RNA
  229. aminoacyl tRNA synthetase
    What glues the AAs onto the tRNA. There is one for each amino acid
  230. How many tRNAs do we need?
  231. How many tRNAs do we have?
  232. Wobble
    Since we need 61 tRNAs and only have 31, we have to alternate position 3 with the inosine and pseudouridine
  233. Prokaryotic Ribosome
    30S and 50S subunits, total 70S
  234. Eukaryotic Ribosome
    40S and 60S subunits, total 80S
  235. Svedburg coefficient
    centrifugation coefficient used in antibiotics
  236. Shine-Dalgardo Sequence
    What prokaryotic DNA use to determine start sequence (like the eukaryotic Kozak sequence)
  237. Ribosome scanning
    Small ribosomal subunit scans (with tRNA attached) by ribosome scanning the mRNA 5' UTR to look for start AUG codon
  238. What happens once tRNA find start sequence?
    Important Initiation factors are recruited (EIF Ii) and then the 60S is recruited
  239. What does every protein start with?
  240. A-site
    donor tRNA-amino acid (amino acid)
  241. P-site
    tRNA growing peptide chain (peptide)
  242. E-site
    tRNA (exit)
  243. Peptidyl transferase
    anzyme that is responsible for elongating the polypeptide chain
  244. Release factor
    Once the stop codon comes into A site, RF Binds to the A site with the help of GTP
  245. Ubiquitination
    sends proteins to be destructed in the proteosome
  246. Secondary structure of proteins
    relies on hydrogen bonding interactions, defined by rotation restriction around phi and psi, alpha helix (interchain H bonding) and Beta sheets (interchain H bonding)
  247. Ramachandran plot
    used to calculate the islands stability of stability by minimizing steric hindrance
  248. Tertiary structure
    3-D structure, relies on the interactions between side chains (not the backbone)
  249. Only covalent bonds in tertiary structure
    Disulfide bonds, cysteine-cystine
  250. Quaternary structure
    Several multiple protein subunits, ex. human hemoglobin, heterotetramer (2 alpha and 2 beta)
  251. Two sites of protein translation
    ribosomes in the cytoplasm and ribosomes on the RER
  252. Direction of protein translation, ribosomes move
    from 5'-->3' (synthesis of protein from N terminus-->C terminus)
  253. Signal recognition protein (SRP)
    Signal sequence at the beginning of the protein signals SRP used
  254. Chemical environment of the mitochondria
  255. Chemical environment of the cytoplasm
  256. ER tanslation
    Signal recogniition sequence on the protein recognized by the SRP-->direct protein into the ER membrane--> enzyme signal peptidase suts off the signal sequence at the beginning of protein
  257. Translation termination
    Once translation is complete, the ribosomal subunits dissociate-->completed protein is sent to the Golgi-->trafficked out of the cell
  258. Protein folding
    goal is to get to the local minimum energy conformation-->decrease Gibb's free energy and increase entropy (of water molecules)
  259. Disulfide bonds
    Don't want to be in the cytoplasm, weaker thand C-C bonds-->mostly found in secretory proteins, lysosomal proteins and exoplasmic domains on the membrane proteins
  260. Where do disulfide bond form in the protein?
    In the hydrophobic interior region of the protein-->they have lower energy
  261. Connotoxin
    importnat for pain management-->uses disulfide bonds to hold peptide architectures together
  262. Anfinsen experiment