Biochem: drugs and diseases

since diabetic pts can't process gluc, FA broken down for E instead. Results in prod of ketone bodies (acetone, acetoacetic acid, B-hydroxybutyric acid). Contains carboxylic acid group which can release H and lower pH resulting in acidosis.

misfolded amyloid-B protein

misfolded superoxide dismutase

Huntingin gene w/ polyglutamine expansion (trinucleotide repeats)

misfolded a-synuclein

Prions

misfolded islet amylodi polypeptide

fetal hemoglobin is not terminated at birth bc mutations prevent formation of tertiary DNA helix in fetal Hb gene promoter region (would normally block fetal Hb prot synth in adulthood). Hb produced in adulthood. Hogs oxygen bc has fetal Hb has high affinity.

Resembles B-thalessemia

results from diff mutations in beta-globin gene

caused by defective a-globin genes

*note: a-globin forms oxygen transporting part of Hb

caused by changes in MCM6 gene

bind to topo 1 and DNA complex which prevents DNA re-ligation and causes DNA damage...apoptosis.

topo I inhibitor

binds to enz and DNA with H bonds; toxicity is result of SSbreaks into DSbreaks during S phase

used in rx of colon cancers

topo I inhibitor

topo I inhibitor

anti-cancer therapies against lymphoid, non-lymphoid leukemia, non-Hodgkins, and Hodgkins lymphomas, testicular, and lung cancers

binds to and inhibits topo II (catenanes), resulting in accumulation of SS or DS DNA breaks, inhib of DNA replication and transcription...apoptosis

topo II inhibitor

topo II inhibitor

topo II inhibitor

topo II inhibitor

DNA pol inhibitor

converted to tri-phosphate form and acts as a chain terminator; incorp into DNA but does not have a reactive 3'OH

DNA damaging agent that cross-links strands or alkylates DNA

Pt-based chemo drug used to treat cancers. Pt complexes react in vivo, binding to guanines and causing crosslinking of DNA....apoptosis

antibiotic

acts as topo inhibitor

rx methicillin resistant MSRA

quinolone

topo inhibitor

rx UTI

antibiotic, fluoroquinolone

topo inhibitor agains +/- bacteria

antibiotic, affects anaerobic microorganisms

reduced to cytotoxic intermediate that destabilizes DNA helix

antiretroviral drug

analog of thymidine that has selectivity for HIV infected cells; results in chain termination

nRTI

analog of cytidine

inhibits both types of rt of HIV and rt of hep B

NNRTI

binds w/in a pocket at an allosteric site near pol active site; distorts catalytical site to block further nucleic acid synth

blocks HSV replication

*contains partial nucleoside structure; incorporated into viral DNA, resulting in chain termination

due to mutation in hnRNP-P2, a prot that binds to pre-mRNA

results from mutations in poly A signal; reduced globin chain synth

from defects in cleavage site on mRNA which results in overproduction of clotting factor...hypercoagulability

due to disorder in splicing

pts have autoantibody that inhibits RNA splciing

due to defect in alternative splicing of BRCA1 gene

co-repressor not released unless high amts of ATR, no transcription of genes since co-repressor still present

Myc mRNA has longer half-life than usual; results in unneeded transcription of genes and too much cell growth

in cancer rx

• inhib RNA pol by intercalating DNA to inhib transC
• inhib DNA pol

more toxic to normal cells than other drugs

in poisonous mushrooms

inhib euk RNA pol II and somewhat RNA pol III

bind to bacterial RNA pol and inhib elongation

rx tuberculosis

*if attack bacterial RNA pol, then also effective against mit RNA pols

results from mutations in eiF-2B (used to recycle eiF-2 in euk translation initiation)

antibiotic

inhib elongation in euk

antibiotic

inhib translocation in prok

antibiotic

inhib translation in prok

antibiotic

resembles 3' end of tyrosyl-tRNA; peptide bond can be formed btw its amino group and carbonyl of peptidyl-tRNA in P site; competes for entry into A site

terminates peptide chain synth in prok and euk

antiobiotic

affects translation in euk

antiobiotic

affects initiation and elongation inprok

antibiotic

affects AA-tRNA binding in prok

contagious, preventable by immunization

caused by corynebacterium diphtheriae-secrets toxin which has enz that can enter cells

covalently links ADP ribose to EF-2, which inactivates EF-2 and inhib prot synth

deficiency in GlcNac-1-P-transferase enz; no manose-6-phosphates on lys enz...not delivered to lysosomes from golgi

results in build-up of inclusion bodies bc lysosomes cannot degrade their stuff

equal amts of insulin and abnormally processed proinsulin released into circulation; ind are neither hypoglycemic or diabetic

due to deficiency in processing enz or mut in cleavage site of pro-insulin molecule

nerve gas, irreversible enz inhib

reacts w/ Ser side chain on acetylcholine esterase (enz in nerve impulses)

used in identifying function of Ser 195 in chymotrypsin

substrate analog of chymotrypsin

binds to active site and irreversibly modifies His 57 residue resulting in inhib

indicates chymotrypsin function of His 57

inhib of monoamine oxidase

binds as a substrate to enz and utilizes enz's own catalytic mech to covalently modify active site...suicide inhibitor

lowers levels of dopamine (parkinson's) and serotonin (depression)

irreversible suicide inhibitor of glycopeptide transpeptidase (critical for bact cell wall synth)

contains B-lactam ring which makes it super reactive

due to a chromosomal translocation that fuses gene for Abl kinase to gene for BCR prot

Rx by Abl kinase inhibitors