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Diabetic ketoacidosis
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.
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Alzheimer's
misfolded amyloid-B protein
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Amyotrophic lateral sclerosis (Lou Gehrig's disease)
misfolded superoxide dismutase
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Huntington's disease
Huntingin gene w/ polyglutamine expansion (trinucleotide repeats)
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Parkinson's
misfolded a-synuclein
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Type II diabetes
misfolded islet amylodi polypeptide
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Hereditary persistence of Fetal Hemoglobin
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
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Sickle cell anemia
results from diff mutations in beta-globin gene
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a-thalessemia
caused by defective a-globin genes
*note: a-globin forms oxygen transporting part of Hb
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lactose intolerance
caused by changes in MCM6 gene
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Topoisomerase inhibitors
bind to topo 1 and DNA complex which prevents DNA re-ligation and causes DNA damage...apoptosis.
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Campothecin
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
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Topotecan
topo I inhibitor
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Lamellarin D
topo I inhibitor
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Topoisomerase II inhibitors
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
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Etoposide
topo II inhibitor
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Amsacrine
topo II inhibitor
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Etoposide phosphate
topo II inhibitor
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Doxorubicin
topo II inhibitor
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Arabinosyl cytosine (AraC)
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
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Cisplatin
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
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Novobiocin
antibiotic
acts as topo inhibitor
rx methicillin resistant MSRA
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Naladixic acid
quinolone
topo inhibitor
rx UTI
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Ciproflaxin
antibiotic, fluoroquinolone
topo inhibitor agains +/- bacteria
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Metronidazole
antibiotic, affects anaerobic microorganisms
reduced to cytotoxic intermediate that destabilizes DNA helix
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Azidodeoxythymidine (AZT)
antiretroviral drug
analog of thymidine that has selectivity for HIV infected cells; results in chain termination
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Lamivudine
nRTI
analog of cytidine
inhibits both types of rt of HIV and rt of hep B
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Efavirenz
NNRTI
binds w/in a pocket at an allosteric site near pol active site; distorts catalytical site to block further nucleic acid synth
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Acyclovir (acycloguanosine)
blocks HSV replication
*contains partial nucleoside structure; incorporated into viral DNA, resulting in chain termination
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POMA (paraneoplastic neuropathies) and neurodegenerative diseases
due to mutation in hnRNP-P2, a prot that binds to pre-mRNA
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a/B-thalessemia
results from mutations in poly A signal; reduced globin chain synth
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DVT/PE
from defects in cleavage site on mRNA which results in overproduction of clotting factor...hypercoagulability
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SLE
due to disorder in splicing
pts have autoantibody that inhibits RNA splciing
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breast and ovarian cancer
due to defect in alternative splicing of BRCA1 gene
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APL
co-repressor not released unless high amts of ATR, no transcription of genes since co-repressor still present
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Burkitt lymphoma
Myc mRNA has longer half-life than usual; results in unneeded transcription of genes and too much cell growth
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Actinomycin D and doxorubicin
in cancer rx
- inhib RNA pol by intercalating DNA to inhib transC
- inhib DNA pol
more toxic to normal cells than other drugs
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a-amanitin
in poisonous mushrooms
inhib euk RNA pol II and somewhat RNA pol III
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Rifampicin and rifamycin B
bind to bacterial RNA pol and inhib elongation
rx tuberculosis
*if attack bacterial RNA pol, then also effective against mit RNA pols
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Leukoencephalopathy w/ VWM or CACH disease
results from mutations in eiF-2B (used to recycle eiF-2 in euk translation initiation)
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Cycloheximide
antibiotic
inhib elongation in euk
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Erythromycin
antibiotic
inhib translocation in prok
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Neomycin
antibiotic
inhib translation in prok
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Puromycin
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
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Ricin
antiobiotic
affects translation in euk
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Streptomycin
antiobiotic
affects initiation and elongation inprok
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Tetracyclins
antibiotic
affects AA-tRNA binding in prok
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Diphtheria
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
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I cell disease
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
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Familial Hyperproinsulinemia
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
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DIPF
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
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TPCK
substrate analog of chymotrypsin
binds to active site and irreversibly modifies His 57 residue resulting in inhib
indicates chymotrypsin function of His 57
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Selegiline
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)
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Penicillin
irreversible suicide inhibitor of glycopeptide transpeptidase (critical for bact cell wall synth)
contains B-lactam ring which makes it super reactive
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Chronic myeloid leukemia (CML)
due to a chromosomal translocation that fuses gene for Abl kinase to gene for BCR prot
Rx by Abl kinase inhibitors
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