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duchesne, fleming, chain, florey |
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natural products (bacteria, mold) organic synthesis |
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antibiotics examples from: bacteria- mold- semi-synthesis- synthetic- |
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bacteria- streptomyces (G+) molds- penicillium semi-synthetic- methicillin (based on penicillin) Synthetic: ciprofloxacin/enrofloxacin |
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staph. auerus found mold growing on them and that the bacteria was dead |
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differences between pathogen and host in physiology/metabolism that allows us to damge microbe instead of pt and limit side effects |
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narrow or broad spectrum- |
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broad- everything all G+ bacteria narrow- abx that only works only on one microbe |
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bacteriostatic or bactericidal- |
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inhibits growth, immune system takes over slows protein synthesis or kills (lysis)-cell wall inhibitors |
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What is the mechanism of action of suprafloxin |
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enzyme is non covalent interaction- not permanent usually preferable |
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enzyme is covalent bonded- permanent inactivation not a great regulation mech. |
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competition of abx can be: |
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uncompetitive competivitce non competitive (allosteric) |
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at enzyme active site inhibitor binds to enzyme and substrate forming a complex that prevents catalysis |
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at enzyme active site structural similarity to substrate/intermediate/product |
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Non-competitive (allosteric) |
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at different site than active site |
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fatty acid synthase (FAS 2) -- enzyme complex -- from EUK allowing for -- |
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series of enzymes that work together multi-enzyme different from EUK allowing for selective tox |
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FAS 2 substrates/products- |
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Substrates- acetyal-CoA, NADPH, ATP Products- Fatty acids, NADP+, ADP +P |
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FAS 2 inhibitor/antibiotics: |
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isoniazid (mycobacterium TerBerculosis) reversible, competitive |
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supercoiling that are different from EUK enzymes that does this |
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Quinolones- Ciprofloxacin, enrofloxacin (Baytril) Reversible, Uncompetitive bacteriacidal- dna cant supercoils completely synthetic |
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Protein Synthesis inhibitors target |
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Protein synthesis inhibitors incldue: |
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tetracyclines(natural) oxasolidinone (Zyvox) macrolides(erytromycin, azithromycin) reversible, competitive |
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how is erythromycin made? |
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multifunctional enzymes and or many enzyme activities Polyketide synthase similar to FAS2 |
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Erythromycin substrates/products; |
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substrates: Malonyl-CoA, NADPH Products: erythromycin precursor, NADP+ |
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Cell wall synthesis starts in- first enzyme envolved= |
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PEP +UDP-NAG -> enolpyruvyl-UDP-NAG-Pi |
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reductase uses NADPH enolpyruvyl UDP-NAG +NADPH -> UDP +NAM +NADP+ + H+ |
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uses atp to form the pentapeptide chain AA + ATP + UDP-NAM -> -> UDP-NADM-L-ALA-D-GLU-?-D-Ala-D-Ala (pentapeptide)+ 5ADP +5Pi |
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after ligase, cell wall biosynthesis shifts from cytoplasm to |
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membrane where MraY takes over |
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forms lipid 1 UDP-NAM-pentapeptide +C55-P (bactoprenol) -> C55-PP-NAM-pentapeptide (lipid 1)+UMP |
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adds a nag, creates lipid 1 glycosyltransferase C55PP-NAM-pentapeptide (lipid1) +UDP-NAG -> C55PP-NAM-(NAG)-pentapeptide(lipid2) +UDP |
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lipid 2 flipped outside of cell membrane to form a cell wall |
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glycosyltransferases polymerize lipid 2 units (b-1,4-linkages, loss of C55PP |
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(only G-) penicillin-binding proteins=PBPs) form cross bridges (transpeptidation Beta-lactams block |
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(Only G-) trim D-Ala = free peptide chains |
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vancomycin (binds to double D-ala structure, works bc only 1 membrane) +beta-lactams block |
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abx cell wall biosynthesis inhibitors are |
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bactericidal B-lactams (penicillins, cephalosporins) prevents transpeptidases |
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reversible, competitive only G+ is HUGE alot of AA-cant get into G- |
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