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Drugs, antibiotics and mechanisms
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42
Biochemistry
Graduate
09/03/2011

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Term
Acyclovir
Definition
cfInhibitor of viral DNA polymerase, eg. Herpes virus. guanine analog. Acyclovir gets converted to acyclovir triphosphate, by the viral enzyme thymidine kinase, which can serve as a substrate for viral DNA polymerase. The lack of a 3'-OH group causes chain termination when it gets incorporate during viral DNA replication.
Term
Tenofovir
Definition
A nucleotide analog that acts as a reverse transcriptase inhibitor (eg. HIV treatment)
Term
Azidothymidine
Definition
Nucleoside analog drug that act by inhibiting reverse transcriptase activity. Have a 100-300 fold greater affinity for reverse transcriptase compared to DNA meaning it binds to retroviral cells that use reverse trasriptase, not heathly body cells. This effectively targets retrovirus activity. Eg. HIV
Term
Didanosine
Definition
Nucleoside analog drug that act by inhibiting reverse transcriptase activity. Have a 100-300 fold greater affinity for reverse transcriptase compared to DNA. This effectively targets retrovirus activity. Eg. HIV
Term
Cytosine arabinoside (Cytarabine)
Definition
The planar configuration of arabinosides induces DNA Damage, and inhibits the activity of DNA polyermase. This is an anti-cancer agent
Term
Vidarabine (adenosine arabinoside)
Definition
The planar configuration of arabinosides induces DNA Damage, and inhibits the activity of DNA polyermase. This is an anti-cancer agent
Term
Decitabine
Definition
Can induce hypomethylation by inhibiting methyltransferase enyzmes
Term
5-azacytidine
Definition
Can induce hypomethylation by inhibiting methyltransferase enyzmes
Term
Ciprofloxacin
Definition
A quinolone drug that inhibits bacterial DNA gyrase. It is used in the treatment of respiratory and urinary tract infections and can be used to treat anthrax.
Term
Camptothecin
Definition
An anticancer drug, binds to and inhibits toposiomerase I activity. The result is DNA breakage.
Term
Etoposide
Definition
An anticancer drug, inhibits the activity of topisomerase II
Term
Rifampin
Definition
An antibiotic from a strain of Streptomyces. Inhibits initiation of transcription. Blocks formation of the first phosphodiester bond by binding to prokaryote RNA polymerase. RNA polymerase of eukaryotes is not affected. Used in the treatment of tuberculosis. Mutation in the gens encoding the target proteins such RNA polyermase and topoisomerases can lead to drug resistance.f
Term
Actinomycin D
Definition
Strain of streptomyces. Binds tightly to double strand DNA. Inhibits transcription and replication in both prokaryotes and eukaryotes. Primarily used as an anti-cancer drug (inhibiting DNA replication and cell division). Not normally used as an antibiotic.
Term
Amanita phalloides
Definition
Produces a toxin called alpha-amanitin which is a potent inhibitor of RNA polyermase II.
Term
Streptomycin
Definition
An aminoglycoside. Binds to 30s ribosomal subunit. Prevents assembly of complete ribosome. Prevents initiation.
Term
Tetracycline
Definition
4 rings (tetra). Binds to the compete (70s) ribosome. Tetracyclines block elongation by preventing access to the incoming aminoacyl-tRNA [Blocks A site]
Term
Minocycline, Doxorubicin, Doxycycline
Definition
Tetracycline: 4 rings (tetra). Binds to the compete (70s) ribosome. Tetracyclines block elongation by preventing access to the incoming aminocyl-tRNA [blocks A site]. These are some other family members. Theme: modification to an antibiotic may alter bacterial resistance to the drug or change absorption or clearance patterns.
Term
Erythromycin
Definition
Macrolide structure (big ring). Binds to the complete (70s) ribosome. Blocks elongation by preventing ribosome movement relative to mRNA. Blocks ribosome translocation.
Term
Chloramphenicol
Definition
Inhibits PROKARYOTIC peptidyl transferase activity (elongation). Not used widely in developed countries. May inhibit mitochondrial ribosomes.
Term
Cycloheximide
Definition
Inhibits EUKARYOTIC peptidyl transferase activity (elongation)It is a simple (relatively cheap) organic molecule that inhibits peptidyl-transferase (elongation) in eukaryotes. Similar mechanism to chloramphenicol. Extremely toxic to eukaryotes. Widely used in laboratories.
Term
Puromycin
Definition
It is a structural analog to a portion of aminoacyl-tRNA. It is toxic to both eukaryotes and prokaryotes - not clinically useful. It blocks elongation after it forms a peptide bond to the growing protein chain. The C-terminal puromycin causes the peptide to fall out of the ribosome P-site, and causes premature transcription termination. [Resembles a tRNA that has an amino acid attached to it but it's not really an amino acid and so it causes chain termination]
Term
Novobiocin and Nidixic acid
Definition
Bacterial gyrase (topoisomerases) can be inhibited by the antibiotics such as the courmarins (including novobiocin) and the quinolones (including nalidixic acid and ciprofloxacin).
Term
Lovastatin
Definition
HMG-CoA reductase catalyzes the rate-limiting step of cholesterol synthesis. Lovastatin competitively inhibits HMG-CoA reductase
Term
DFP (di-isopropyl fluorophosphate)
Definition
It is an irreversible inhibitor of acetylcholine esterase which normally cleaves the neurotransmitter acetylcholine. This inhibition is lethal. DFP binds covalently to the serine in the active site and blocks its catalytic action. This posion is the ancestor of organophosphorus nerve gase [Sarin] and also of pesticides. The active-site serine froms normally a covalent intermediate during catalysis. DFP blocks this reaction and acetylcholine accummulates
Term
Aspirin
Definition
It is a drug that is used at low dose for reduction of blood clotting. It inhibits irreversibly COX in all cells. It acetylates a serine in the channel of the active site. Cyclooxygenase (COX) is an enzyme that uses arachidonic acid as substrate. COX forms different eicosanoids (prostaglandins, thromboxane and leukotrienes) dependtent on cell type. Platelets need COX for thromboxane (which stimulates blood clotting). Endothelial cells need COX for prostacyclin formation (which prevents blood clotting). Endothelial cells synthesize new COX. Platelets cannot synthesize new COX as they do not have a nucleus. The prostacylin/thromboxane ratio is shifted in favor of prostacyclin. Platelets forms less thromboxane than normal until new platelets are formed (about 10 days). This is why aspirin treatment has to stop before surgery at least for a week.
Term
Systemic Lupus Erythematosis
Definition
Auto Immune disease. Cause by antibodies that react with the U1 SnRNP RNA component of the spiceosome. Prevent normal splicing of mRNAs.
Term
B-Thalasemmia
Definition
Mutation in the B-globin gene thate generate additional splice sites within mRNA. --> abnormal B-globin. Abnormally long tetramers--> easy target for spleen.
Term
Limb girldl muscular dystrophy
Definition
Alteration in gene that causes new splice site, within an exon--> a defective protein
Term
Diptheria Toxin
Definition
Inactivates EF-2 (EF-G for prokaryotes)
Term
Mercamptoethanol
Definition
Reduce/cleave disulfide bonds
-
Term
Alzheimers
Definition
Disfuntional Ubiquitin protein that targets misfolded/old/defective proteins for degredation in proteosome.
-Makes damaged proteins stable and accumilate in the brain

Same mechanism as Prions disease
Term
Prions
Definition
Proteinaceous infectious agent-Single infectious protein resulting from Changing of a-helix to B-sheet in prion protein (PrP)found in brain tissue.--> Infected Prp^sc protein acts as template for large formation of abnormal Prp Sc
Term
Effects of definciencies in glycolysis on Hb 02 affinity
Definition
Hexane kinase-->2,3, BGP--> Pyruvate kinase.

2,3 BGP stabilized taught state of Hb and deacreased affinity for O2.

X Hexokinase= decreased 2,3 BPG = increased affinity= left shift in curve
X Pyruvate kinase= Increased 2,3 BPG = decreased affinity = right shift in curve
Term
Fetal Hb
Definition
increased y(gamma)2 side chain. A2Y2=> increased affinity for 02 (can steal it from mom)

(Binds 2,3 BPG less tightly)
Term
Lysyl oxidase
Definition
Extracellular enzyme, needs copper as a co-factor
Deaminates lysine to Form allysine or hydroxyalliysine residues for cross linking.

Needed for cross linking of both elastin and collegen fibers
Term
Ehlers-danlos syndroms
Definition
Result from Gene mutation for pro-a-chains

Defects can be found in Prolyl/ lysyl hydroxilase( Hydroxilation for lysine/proline)(Ca+2 cofactor)

Lysyle oxidase(Needed for cross linking between chains (copper cofactor)

Procollagen peptidases-cleaves collegen to insoluble form in ECM

Results in hypermotility of joints/ fragile/hyperstretching skin/ fragile blood vessels
Term
Osteogenesis Imperfecta
Definition
Autosomal Dominate Brittle bone syndrum- Bones break easily especially in childhood, and blue schlera in man types

Type I-mildest
Typle II-Most severe(death in utero)
Term
Marfans SYndrom
Definition
X gene that codes for fibrillin(Used to scaffofold to make elastin from tropoelastin in ECM
(Side note-lysines/prolines not mostly not hydroxilated in elastic. Needs lysyl oxidase for crosslinking therefor copper)

Marfans long limpbs/lens dislocation/risk of annuerism
Term
Barths syndrome
Definition
Deficiency in cardiolipin-special phospholipid in inner mitochondrial membrane. mainly 18:2 6...Rare but severe cardiomyopathy
Term
Cystic Fibrosis
Definition
Fked up CFTR (cystic Fibrosis Transmembrane Regulator)(ABC :ATP binding cassette channel) From a single phenylalanine mutation.
Term
Apo Gene etc.
Definition
RNA editing in liver. CYTIDINE DEAMINASE introduces early stop codon . So intestine has a shorter apolipoprotein.

Glutamate Receptor in brain.Adesine deaminase. Changes Ca+2 permiability of an ion channel. Required For Proper devolopment

Troponin=Alternative splicing;
Term
Trypanosome (chagas disease) and leishmania
Definition
parasites that use extensive RNA edditing(adding Poly U's) to stay ahead of immune system
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