Methotrexate- targets S-phase - inhibits metabolism of folic acid (needed for de novo sythesis of nucleotide thymidine, required for DNA synthesis) - treatment of cancer, autoimmune diseases
5-flurouracil- targets S-phase - irreversible inhibition of thymidylate synthase (required for DNA synthesis) - treatment of cancer
Hydroxyurea= hydroxycarbamide - targets S-phase - inhibits ribonucleotide reductase (decreases production of deoxyribonucleotides) - antineoplastic, used in myeloproliferative disorders (polycythemia vera, sickle-cell ...
Bleomycin- targets G2-phase - induction of DNA strand breaks - used to treat cancer (Hodgkin's disease)
Paclitaxel- targets M phase - interferes with microtubule breakdown during cell division - treatment against cancer
Vincristine- targets M phase - binds to tubulin protein, stopping the cell from separating its chromosomes during metaphase - treatment for cancer (ALL, AML, Hodkin's disease)
Vinblastin- targets M phase - disrupt microtubule synthesis - treatment for cancer (Hodgkin's lymphoma)
Quinolones- inhibit DNA gyrase (prokaryotic topoisomerase II), preventing DNA replication and transcription - most active against aerobic gram-negative bacteria - Levofloxacin- Ciprofloxacin- Moxifloxacin - current ...
Alport disease- improper assembly of type IV collagen - glomerulonephritis (glomerular basement membrane with "basketweave" appearance) - hearing loss - blood in urine - proteinuria
Goodpasteure syndrome- autoimmune disease in which antibodies attack the basement membrane (collagen type IV) in lungs and kidneys - blood in urine - proteinuria
Inhibition of protein synthesis by antibiotics- Chloramphenicol binds to the 50S rRNA and inhibits formation of a peptide bond - Erythromycin binds to the 50S rRNA and prevents movement along the mRNA (translocation) - Aminoglycosides interfere with ...
Nitrogen BalanceNegative balance:- protein malnutrition (kwashiorkor)- dietary deficiency of even one essential amino acid- starvation- uncontrolled diabetes- infection Positive balance:- growth- pregnancy- convalescence ...
Cyanide- deadly poison - binds irreversibly to cytochrom a/a3 - causes tissue hypoxia - source: burning pulyurethan, byproduct of nitroprussid - antidote: nitrites (convert hemoglobin to methemoglobin, which ...
Carbon monoxide- binds to cytochrom a/a3 and hemoglobin, displacing oxygen - headache, nausea, tachycardia, tachypnea - lips and cheeks turn a cherry-red color - source: gas grills, vehicle exhaust, house fires
Oligomycin- poisonous - inhibitor of the ATP synthase - created by Streptomyces
Biosynthesis steps promoted by insulinConversion of glucose to acetyl CoA:- glucokinase- PFK-2 (dephosphorylation)- Pyruvate dehydrogenase (dephosphorylation) Fatty acid synthesis- Acetyl CoA carboxylase (dephosphorylation)- Fatty acid synthase ...
Associations with ketoacidosis- Polyuria, dehydration, and thirst - CNS depression and coma - K+ depletion - decreased plasma bicarbonate - breath with sweet or fruity odor, acetone
Drugs that disrupt pyrimidine synthesis- Leflunomide: inhibits dihydroorotate dehydrogenase - Metrotrexate (MTX), trimethoprin (TMP), pyrimethamine: inhibit dihydrofolate reductase (↓dTMP from dUMP) - 5-fluorouracil (5-FU): forms 5-F-dUMP, ...
Drugs that disrupt purine synthesis- 6-mecaptopurine (6-MP) and its prodrug azathioprine. inhibit de novo purine synthesis - Mycophenolate and ribavirine: inhibit IMP dehydrogenase (↓GMP)
Defects in DNA repairNucleotide excision repair --> Xeroderma pigmenosum Mismatch repair --> Lynch syndrome Nonhomologous end joining --> Ataxia telangiectasia, Fanconi anemia
Ethanol metabolism↑ NADH/NAD+ ratio in liver causing:- Pyruvate --> lactate (lactic acidosis)- DHAP --> Glycerol 3-P (combines with fatty acids to make triglycerides --> hepatosteatosis) - disfavors TCA production of ...
