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Terms in this set (57)
improper functioning of muscle allows gastric juice to leak into esophagus (heartburn). Antacids (CaCO3) neutralizes the acid by coverting it to CO2 OR Omeprazole is a protein pump inhibitor.
Antacids (CaCO3) neutralizes the acid by coverting it to CO2 OR Omeprazole is a protein pump inhibitor
CO2 + H2O <--> H2CO3 <--> H+ + HCO3- (CO2 is the WA, HCO3- is CB). CO2 is removed through lungs (open system), H+ and CO3- can be removed in urine via kidneys). Breathing out heavily after intense sprint - get rid of acid (due to lactic acid buildup).
Sickle Cell Anemia
Glu --> Val on Hgb B subunit (missense mutation). Creates hydrophobic contact position on outer surface of the protein, interacts with acceptor pocket of Phe and Leu on another molecule. Sticky patch not exposed ir Hgb is oxygenated, sickling more severe in deoxygenated state. HgbS aggregates into long fibers, distorts cytoskeleton causing change in morphology to sickle shape. Reduces life span of RBC, insuff O2 to tissues, pain, vision problems, delayed growth. Patients told to avoid high altitude and exercise.
Osteogenesis Imperfecta Type II
Gly --> Asp, causes steric hindrance in tight coiling of collagen triple helix --> collagen deformation. Perinatal lethality b/c bones and cartilage not formed
Cys --> Trp or Arg in Androgen Receptor protein --> disruption of Zinc finger motif. Receptors can bind the hormones but unable to interact with DNA preventing transcription of many genes. Genotypically male but phenotypically female.
Inhibits AChE so ACh can continue to act on AChR and activate it. Binds noncovalently to prevent hyper-signaling. In Alzheimer's patients, Ach level is significantly decreased. Serves to increase Ach levels in neurosynapse.
Oral Rehydration Tx
Na+-Glucose Co transporter in intestinal epithelial cells is one of the only membrane transporters that works in cholera. Allows Na+ influx to occur Adding Glucose to saline greatly improved clinical treatment of dehydrated patients.
Use rational drug design, 3D structure of Indinivir mimics the dipeptide region recognized by the enzyme HIV protease. Drug binds the active site blocking access for the real substrate via Asp residues. Works as Competitive inhibitor. Used to treat HIV
Neurodegen dz & Amyloid fibers
Amyloid plaques - rich in B strands that come together to form extended B sheet structures (resistant to degradation). Individuals w/ Neurodegenerative diseases often show deposition of Amyloid B proteins (amyloid plaques)
PrPSc is rich in Beta strands - same structure as PrPc normal form but folds differently. PrPSc favors aggregates
Phe residue in CFTR protein is deleted. Protein is folded incorrectly, cannot be inserted into membrane. High NaCl concentration in surface fluid inactivates bacteriocidal substance secreted by epithelial cells. Mucus coating becomes very thick, provens haven for pathogenic bacteria --> lung disease and damage. Tx: add chaperone to help fold protein
Hexokinase vs Glucokinase
Hexokinase has a low Km and low Vmax for glucose (found in the brain) wherease Glucokinase has a higher Km & much higher Vmax (hepatocytes). Both enzymes are isozymes, permit fine tuning of metabolism to meet the needs of the tissue.
Creatine Kinase converts creatine creating to Phosophcreatine to increase energy store, break down to yield ATP. Used at site of muscle for movement, Different forms of CPK are found in different tissues. Leakage into blood serum indicates tissue damage (myocardium specific levels used to dx MI)
DIFP can form a covalent bond with Chymotrypsin and AchE via their active site Serine residues (irreversible competitor)
Malathion converted to metabolically active Malaxon (quick process in insects). Malaoxon acts as irreversible inhibitor at Serine active site of AchE, preventing Ach breakdown and termination of signal. Relatively low human toxicity because conversion of Malathion in humans is slow process
Ex: Soman, Sarin, Tabun irreversibly bind AChE at Serine active site. Nerve gasses lead to hypersignaling of Neuron - signal cannot be turned off
PCN irreversibly inhibits bacterial enzyme Glycosidal transferase at active site (forms cross links of cell wall) b/c it has sim structure to substrate. Beta lactamase is bacteria evolved enz that inactivates PCN by cleaving B lactam ring. Augmentin is used in abx tx b/c inhibits Beta lactamase.
Mark 1 Auto injector Kit
Nerve gas irreversibly inhibits AchE --> Hypersignaling. Auto injector kit includes 2-PAM (Pralidoxime) to regenerate the active site (cleaves cov bond b/w nerve gas and AChE) and Atropine which is competitve inhibitor w/ Ach on AChR to reduce hypersignaling.
Cdiff bacteria is spread via fecal-oral via spores, can arise if nml flora is been disrupted by abx. In hospital, alcohol based hand cleaners do not kill spores, need UV light
Nonsense and frameshift mutations in HBB (human beta globin gene) lead to less Beta globin production and therefore less Hgb Leads to severe anemia, delayed growth, bone deformatives, varies by type of mut and severity of dz
Sodium nitrates (preserved meats) converted to nitrous acid (HNO2) which is DNA reactive and leads to deamination
Benzopyrene in cig smoke turns DNA reactive after hydroxlyation in liver --> alkylates purines, adds large bulky group (requires Nucleotide excision repair). Nicotine in cigarette smoke binds NAChR increases NT and is thought to stim reward circuits.
Nitrogen mustard gas
An akylating agent that causes interstant cross links b/w G residues. Leads to replication fork stalling, DNA damage response --> apoptosis.
Inability to perform nucleotide excision repair, thereby cannot repair Thymine dimers caused by UV light and akylation by cig smoke Skin hypersensitive to sunlight, highly susceptible to cancer, early death. Also need to avoid cigarette smoke.
XPD and XPB (are helicases used in nucleotide excision repair and RNA transcription), mutations in them lead to this disease
Hereditary Nonpolysis Colorectal Cancer (HNPCC, Lynch Syndrome)
Mutations in mismatch repair pathway. If both copies of the gene have the mutation, rapid acc of mut and oncogenes
mutations in homologous end joining. decreased production of all types of blood cells (affects bone marrow)
Breast/Ovarian cancer w/ BRCA gene
mutations in homologous end joining
mutations in nonhomologous end joining. spider veins, cerebellar degeneration, immunodeficiency, cancer susceptibility, radiation sensitivity
Is an endotoxin, found on Gram - bacteria, Lipid A is the toxic portion. Binds TLR on macrophages and dendritic cells, triggers release of inflamm cytokines Leads to fever, hypotension and septic shock
Anti cancer drug that inhibits tyrosine kinsae activity of bcr-abl oncoprotein. Blocks the active site of the kinase via competitive inhibition effective against CML and GISTs
Proteolytic cleavage of the proenzyme leads to activation. Made in the pancreas, if secreted too early, zymogen granykes cause damage to pancreatic tissue.
Heterotropic allsteric regulator of oxygen binding to Hgb, binding helps unloading of O2 in tissues. His interacts with (-) charges on BPG At higher altitude, in response to low O2, body increases amt of 2-3 BPG
FHgb has higher aff for O2 because lower aff for 2-3 BPG. Change of AA from His --> Ser, therefore cannot interact w/ (-) charges. Allows transfer of O2 from Hgb to FHgb
glucose is taken up by cells in the body that contain GLUT transporters. Skeletal muscle, liver, adipose have insulin receptors that trigger insertion of more GLUTs into membrane
Death cap mushroom (Amanita Phalloides) poisoning
alpha-amanitin binds to conserved bridge helix of RNA pol II and inhbits translocation, flexibility of the bridge is needed and the toxin greatly reduces this Caues liver and kidney disfxn, need liver transplant to survive. Drugs and abx are used but not effective ~ 20-30% mortality rate
Actinomycin D (Dactinomycin)
Binds DNA at transcription initiation complex and prevents elongation of RNA chain by RNA pol (both euk and prok). used in chemotherapy drugs (affects quickly dividing cells)
Binds RNA channel on RNA pol and prevents RNA extrusion from the polymerase. Does not affect euk cells b/c diff RNA pol in euk Antibiotic used to tx TB, 10% get dz if not treated, others carry latent infection (immune system becomes weakened --> develop dz)
Diamond blackfan anemia - mutations in the ribosomal proteins itself Dz with severe bone marrow failure
Cartilage hair hypoplasia - mutations in Rnase for trimming of ribosomal proteins growth retardation, immunodeficiency, anemia, predisp to CA, gastro malabsorp
Treacher Collins syndrome, Blooms syndrome, Werner syndrome - mut in Pol-1 transcription factors
Bowen-Conradi syndrom - mutation in the methyltransferase which is used to modification
Spinal Muscular Atrophy (SMA)
SMN protein facilitates assembly of spicesome snRNPs, also fxns in neuronal mRNA transport. SMN1 gene is mutated but still have SMN2 (allows survival). SMN2 cannot produce functional SMN protein due to C-->T change (cannot bind exonic splicing enhancer). Degeneration of alpha motor neurons in brain stem and spinal cord --> muslce wasting and paralysis. Nusinersin facilitates exon-7 inclusion by blocking intrinsic splicing silencer in SMN2, also RG-7916 facilitates exon-7 inclusion (in trials).
Mutation in FII gene (codes for prothrombin --> thrombin), mut in the 3' UTR increaes levels by facilitating 3' more efficient end processing of prothromb mRNA. Wild type has suboptimal dinucleotide and 3' flanking elements, changed to optimal CA. Leads to hypercoagulability (disorder than increases risk to thrombosis due to alteration of constitution of the blood)
Hutchinson Gilford Progeria
Change from cytosine to thymine. Normally this is a silent mutation but results in alternative splicing site. Results in loss of 150 nucleotides. Results in alopecia totalis, beak nose, localized scleroderma, small face and jaw, wrinkled skin, stiff joints.
autoimmune disease involving antibodies against AchR, cannot activate muscle. progressive muscle weakness that worsens over time
binds AchR and prevents activation. short term muscle relaxant that aids endotracheal intubation
Ras and CA
mutations can cause Ras to be active all the time (always GTP bound), signaling cascade for MAPKK pathway (stim TF and cell fivision) always on. Leads to tumor growth and CA (issues with this are found in 25% of human cancers, lots of lung/colon/pancreatic CA)
HER2 monomers can homo or hetero dimerize without a signal. The drug (antibody) binds HER2, reduces dimerization and reduces signaling preventing cells from activating CDKs associated with over-proliferation 30% of breast CA overexpress HER2
Insulin binds insulin receptor on cell surface, stim Ras/MAPK kinase cascade and PDK/Akt kinase cascade. Insulin signaling --> increases # of glucose transporters (stored in vesicles) at plasma membrane through PI3 activity
block the beta su of the Beta adrenergic receptor, prevents alpha protein from activating adenylyl cyclase reduce effect of excitement and exercise on heart rate and force of contraction, reduce dilation of blood vessels, reduce tremor and breakdown of glycogen. Used to tx cardiac arrythmias.
Causes G-apha stimulated to stay on indefinitely, toxin causes ADP ribosylation of G-alpha stimulated so it cannot be hydrolyzed GTP --> GDP, adenylyl cyclase keeps making cAMP, activating PKA. PKA causes CTFR (chloride channel) to be open, NA+ H+ to activate. Lots of Na+ and Cl- going out of the gut cells, triggers massive water loss --> diarrhea
Pertussis toxin (made by bordetella pertussis in the lungs) causes covalent modification of G-alpha inhibitor so prevents it from binding GTP and inhibiting adenylyl cyclase. Leads to large increase in cellular cAMP Not completely understand
Angiotensin II is ligand that acts on GPCR on adrenal gland--> activates IP3 and DAG --> system controls blood pressure. Drug inhibits ACE (convert extracellular angiotensin I to active ligand angiotensin II). No ligand to act on receptor --> BP controlled
Vanishing White matter disease
EIF2-GTP protein binds the Met-tRNA and helps it bind the pre-initiation complex (GTP-->GDP). After initiation starts, EIF2B exchanges the GDP for a GTP regenerating EIF2-GTP so it can be re-used and start translation initiation of another mRNA. Stress results in pn of EIF2-GDP. EIF2-GDP-Pn cannot be converted back to EIF2B-GTP. Childhood Ataxia with diffuse central nervous system hypomyelination (CACH). Growth and maintenance of myelin sheath is impaired. Stressors like fever, mild head trauma and fright can trigger worsening of sx.
Abx that affect translation
Streptomycin - binds 16s rRNA of small subunit, causes misreading and inhib of initiation Used for TB
Chloramphenicol - binds 50S subunit and inhibits peptidyl transferase Used for conjuctivitis, meningitis
Tetracyclin - binds to 30S subunit and inhibits binding of aminoacyl-tRNA to A site used for syphilis, cholera, plagye
Erythromycin - binds to 30S subunit and prevents translocation used for bacterial respiratory and skin infections
inactivates eEF2 by causing ADP ribosylation of His residue, preventing translocation and elongation from ocuring Inflammation of nerves, myocarditis, swelling of neck, kidney problems
toxin from castor bean, causes depurination of A residue in 28S rNA using its rRNA N-glycosylate activity, this A residue is critical for binding elongation factors. nausea, vomiting, diarrhea, abdominal pain, liver and kidney disfunction
Hereditary Colon CA - APC
results in mutation in APC gene (tumor supressor gene). Functional APC gene turns off B-catenin (active form promotes cell division and growth). Without active APC protein, B-catenin promotes cell proliferation. Causes cancer.
Activation of MAPKK pathway leads to production of cyclins, cyclins bind CDKs promoting cell division. lots of oncogenes are associated with this
Colchicine, Paclitaxel (Taxol), Vinblastine inhibit formation of the spindle and microtubules, cannot satisfy metaphase checkpoint. Leads to cell cycle arrest and apoptosis if cannot satisfy the checkpoint, kills CA cells. Used as chemotherapy drug.
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