Drugs and Mechanisms of Action Flashcards
Sulfa Drugs (Sulfonamides)
Inhibit bacterial folate synthesis from PABA
Trimethoprim
Inhibit bacterial dihydrofolate reductase
Methotrexate
Inhibits eukaryotic dihydrofolate reductase (used as an anticancer agent)
Hydroxyurea
Inhibits ribonucleotide reductase (this enzyme converts ribonucleotides to deoxyribonucleotides)
Mycophenolic acid
Inhibit GMP synthesis from IMP (Purine nucleotide biosynthesis)
5-Fluorouracil
Inhibit thymidylate synthase (converts dUMP to dTMP and requires tetrahydrofolate)
Allopurinol
Inhibits xanthine oxidase (this enzyme converts hypoxanthine to xanthine and xanthine to uric acid)
NSAID and aspirin
Inhibit cyclooxygenase and used as anti-inflammatory drug.
Repeated infections, reduced T and B cell immunity. Accumulation of dATP results in inhibition of proliferation of T and B lymphocytes due to inhibitory effect of dATP on Ribonucleotide reductase
Severe combined immunodeficiency (autosomal recessive)
Enzyme deficiency that leads to SCID
Adenosine deaminase (ADA), enzyme in the catabolism of purine nucleotides. It converts adenosine to inosine.
Repeated infections and T-cell immunodeficiency
Purine nucleoside phosphorylase deficiency
Enzyme deficiency: Purine nucleoside phosphorylase (as described in the name), enzyme in purine nucleotide degradation.
Clinical Features include: Self mutilation, hyperuricemia, mental retardation
Lesch-Nyhan syndrome (X-linked recessive)
Enzyme deficiency that causes Lesch-Nyhan syndrome
HGPRT deficiency (Enzyme involved in the salvage of purine bases hypoxanthine and guanine)
Clinical diagnosis for the following signs and symptoms: Megaloblastic anemia (due to reduced pyrimidine biosynthesis) growth retardation
Orotic aciduria
Function of PRPP Synthetase
Synthesis of PRPP for purine and pyrimidine nucleotide synthesis
Function of phosphoribosyl amidotransferase
Regulated/committed enzyme of purine nucleotide synthesis; Activators: PRPP; Inhibitors: ATP and GTP
Function of Xanthine oxidase
Enzyme of purine degradation; forms uric acid from xanthine; Also forms xanthine from hypoxanthine; Inhibitor: Allopurinol (Febuxstat)
Function of HGPRT
Enzyme of purine salvage pathway; deficiency causes Lesch Nyhan syndrome
CPS-II
Regulated enzyme of pyrimidine biosynthesis (Inhibited by UTP; Activated by PRPP); cytosolic enzyme
UMP synthase (OPRT and OMP decarboxylase)
Enzyme of pyrimidine biosynthesis; deficiency of the enzyme results in Orotic aciduria
Ribonucleotide reductase
Converts ribonucleotides to deoxyribonucleotides; Inhibitor: Hydroxyuria
Thymidylate synthase
Forms dTMP from dUMP for DNA synthesis:
Inhibitors: 5-Flurouracil, methotrexate (dihydrofolate reductase inhibitor)
Clopidogrel
Antiplatelet drug: reduces chance of blood clot formation
A patient is suspected to have a genetic cause associated with his symptoms. A test is given which detects a deletion of 500,000 base pairs of DNA from his chromosome 7. What
test was used to detect this?
1. FISH
2. cDNA array
3. G-banding
4. PCR RFLP
cDNA array
Silent mutations
Have no effect on the amino acid produced by a codon because of redundancy in the genetic code
Missense mutations
still code for an amino acid, but not the correct amino acid
Nonsense mutations
Change an amino acid codon into a stop codon, nearly always leading to a nonfunctional protein
Transcription factors 3 modes of action
- Competition
- Quenching
- Blocking
Competition of transcription factors:
The repressor binds enhancer sequence of the DNA and competes with enhancer proteins
-Reduces transcription by preventing enhancer protein binding
Quenching of transcription factors:
The repressor binds to the activator protein and blocks its ability to bind the DNA site
-Repressor soaks up the activator protein
-Activator protein is not able to bind to the DNA
Blocking of transcription factors
The repressor binds to the activator protein’s activating domain and prevents it from interacting with general transcription factors
Epigenetics
A change in the expression of a gene that changes the phenotype without permanently changing the gene itself (DNA sequence) but instead involves changes in chromatin structure
miRNA Drosha role
Processes long primary-miRNAs to pre-miRNA hairpin structures
miRNA Dicer
Further processes them to single stranded RNA and initiates the formation of the RNA-induced silencing complex (RISC)
Regulation by miRNA
- Inhibition of translation on the ribosome
- Degradation of the target mRNA
Euchromatin (E)
Less condensed, more transcriptionally active
Heterochromatin (H)
Condensed chromatin, less transcriptionally active
Telomere
-At the ends of chromosomes
-Repeated sequences that allow the ends of the chromosomes to be replicated
Centromere
-Centric heterochromatin
-Persists throughout interphase
-Constricted region that holds sister chromatids together
-Also the site of kinetochore formation
Replication origin
-Location where DNA replication begins
Ribosomes types
- Membrane bound ribosomes
- Free ribosomes
Function: Sites of protein synthesis (translation)
COP-1 coated vesicles
-Retrograde transport
-CGN back to rER
COP-II coated vesicles
-Anterograde transport
-Carry newly synthesized proteins from rER to CGN
