exam 3: toxins and diseases

mycophenolic acid

inhibits IMP DH

- prevents IMP --> XMP rxn

- IMP DH is needed for growth of T-cells and B-cells

glutamine analogs

inhibit glutamine amidotransferases and therefore inhibit nuc. biosynthesis

- affect normal cell AND tumor cells

- inhib. formation of erythrocytes, lymphocytes, intestinal epithelial cells, and hair-forming cells

methotrexate & aminopterin

comp. inhib. of DHFR

- directly prevents hydrofolate --> THF rxn

- indirectly prevents N5-methylene THF formation (cofactor for TS)

- can cause abortion

5-flurouracil

Suicide inhibitor of thymidylate synthase

- more direct than methotrexate and aminopterin

- acts via the pyrimidine salvage pathway

sulfa drugs

sulfonamides (sulfonic acid + amide) that act a antibaterial agents by preventing syn. of THF and folic acid in bacteria

- structural analogs of p-aminobenzoic acid (folic acid precursor)

trimethoprim

comp. inhibits bacterial dihydrofolate reductase

- more "distant" THF analog

- type of sulfa drug

Severe Combined Immunodeficiency (SCID)

lack of adenosine deaminase enzyme (ADA)

- no ADA, buildup of deoxyadenosine, buildup of dATP, RNR shutdown => no DNA synthesis/lymphocytes (B & T cells) and failure of immune system

purine nucleoside phosphorylase

lack of this enzyme causes similar symptoms to SCID, but less severe

Gout

buildup of uric acid crystals in joints due to excess xanthine oxidase

- treatment: allopurinol (XO suicide inhib.)

Acyclovir (Zovirax)

treatment for herpes simplex virus

- inhibits viral DNA polymerase as a structural analog of nucleoside bases

- activated by TK gene in HSV

- acts via the pyrimidine salvage pathway

DPD inhibitors

increase 5-FU activity

Ciprofloxacin (Cipro)

a quinolone antibacterial drug that works by inhibiting DNA replication and causing cell death

- binds type II bac. topoisomerase IV & DNA gyrase

Doxorubicin

anticancer agent that works by intercalating and inhibiting progression of type II topoisomerase

- same mech. as Cipro but works on humans (not bacteria)

Rifamyacin B/Rifampicin

bacterial transcription inhibitor

- prevents chain elongation

- very effective against TB

Actinomycin D (Dactinomycin)

anticancer agent that inhibits eukaryotic replication AND translation

- binds tightly to dsDNA

- intercalates into dsDNA

alpha-amanitin

Inhibits RNA polymerase II in eukaryotes

- one of the most toxic organic compounds in the world

- found in mushrooms ("destroying angel" or "death cap")

hydroxyurea

ribonucleotide reductase inhibitor

- suppresses DNA transcription

- involved in chemotherapeutic techniques

Lesch-Nyhan Syndrome (Juvenile Gout)

HGPRT (hypoxanthine-guanine phosphoribosyltransferase) deficiency that causes a buildup of hypoxanthine --> buildup of uric acid in blood

- prominent in young males/X-linked recessive inheritance

- causes neurological problems

Kidney Stones

excess uric acid forms crystals in kidney due to excess XO

- treated by XO inhibitors

AMP deaminase deficiency

deficiency of myoadenylate deaminase enzyme causes muscle fatigue and cramps after exercise

- prevents AMP --> IMP rxn

xeroderma pigmentosum

defect in nucelotide excision repair leading to damaged DNA bc of radiation

chloramphenicol

Blocks peptidyltransferase at 50S subunit and assists w/ A-site binding

erythromycin/azithromycin

binds to 50S rRNA and prevents movement along mRNA

-macrolide antibiotics

tetracycline

inhibits aminoacyl-tRNA binding

streptomycin

inhibits chain termination & changes shape of 30S rRNA, causing it to be read incorrectly

puromycin

binds to A-site and receives peptide from transpeptidase

- prematurely aborts peptide syn.