Week 2 Richter Lectures Flashcards
a group of genes, regulated together by transcription from a single promoter that produces polycistronic mRNA
operon
repressor binds to operator= what to transcription
inhibits
what is used to break down lactose
lac operon (found in prokaryotes)
Trp bound to repressor causes what to transcription
inhibits (Trp operon-found in prokaryotes)
acetylation of histones does what
turns on gene expression
methylation of histones does what
turns off gene expression (silences it)
what often happens to cancer (acetylation and methylation example)
oncogenes need to be methylated (to silence the gene)
drug used in anti-cancer chemotherapy that can reverse gene silencing, reduce proliferation, and trigger apoptosis
Vorinostat (drug that inhibits HDAC)
remove acetyl groups from chromatin, which often silences gene expression
histone deacetylases (HDACs)
what happens when gene expression is activated that should instead be silenced
cancer
if these get methylated, they won’t be able to stop cancer
tumor suppressors
3 functions of transcription factors
- DNA binding domain
- dimerization domain
- activation domain
a DNA-binding domain that allows TFs to insert themselves into grooves of DNA; Cys or His residues bound to Zn2+
Zinc finger
what receptors are basically transcription factors
nuclear receptors
DNA binding domain that has + and - charge by ionic interaction
basic domain
mutation of Vitamin D receptor leading to vitamin D deficiency
Rickets
mutation in thyroid hormone receptor leads to low T3 and thyroxine
Hypothyroidism
mutation of cortisol receptor leading to high levels of corticosteroids
Cushing’s Disease
nuclear receptor used in birth control (combination of 2)
estrogen/progesterone
mutation of retinoic acid receptor; can cause developmental defects in embryo and fetus
retinoic acid derivatives
used for acne and is contradicted during pregnancy
retinoic acid
2 dimerization domains
leucine zipper and HLH (helix-loop-helix) domain
All transcription factors are what
dimers
leucine residues are where on the helix (for leucine zipper)
on the same face
transcription factor class that control fundamental architectural plan of developing embryo
helix-turn-helix
(from Hemeobox (Hox) genes)
key process in gene silencing and defense against viral infections
RNA interference (RNAi)
main player in RNA interference (gene silencing)
miRNA
activates and cleaves mRNA during miRNA synthesis and gene silencing
RISC (RNA induced silencing complex)
regulated process during gene expression that results in a single gene coding for multiple proteins
alternative splicing
atleast one specific what is required per amino acid during translation
tRNA
what is the form of tRNA ready to be used in translation; and connects to amino acid
aminoacyl-tRNA
used as a signal initiation of translation; how the cell knows this RNA needs to be translated
7-methyl guanosine cap
a longer polyA tail means what for translation
most likely to happen
Initiation step of translation:
- binding of methyl cap
- joining of elF4B
- 43S complex
- joining of 60S with 43S at start codon (starts when it hits its first AUG)
elongation of translation sites:
A: recruits incoming aminoacyl tRNAs
P: growing tRNA (from P to A)
E: exit site (for empty tRNA)
many mRNAs have multiple _____ bound that allows translation of many proteins
ribosomes
this happens when the release factor enters the A site
termination of translation
this antibiotic binds to 30S subunit and causes misreading of genetic code; also inhibits initiation
aminoglycoside (streptomycin/gentamicin)
this antibiotic binds to 30S acceptor site (A site) and is just in the way
tetracycline
this antibiotic binds to 50S subunit and inhibits peptide bond formation
chloramphenicol
this antibiotic binds to 50S and blocks transferase reaction (inhibits enzyme that catalyzes formation)
erthromycin
this antibiotic binds to A site and acts as peptidyl acceptor- aborting elongation (blocks elongation)
puromycin
what blocks translation by inhibiting mTOR (mammalian target of rapamycin); inhibiting elF4E inhibits translation; also prevents blood vessel walls from thickening after angioplasty
rapamycin
addition/removal of AA’s through signal sequence(marks protein for secretory pathway)/ubiquitination (degradation by proteasome)
post-translational modification
4 steps of post-translational modification
- add/remove AA’s
- add carbohydrates
- add lipids
- reversible regulation through chemical modifications
what post-translational modification is essential for proper protein folding
N-glycosylation
addition of lipids to protein through post-translational modification
myristylation
amino acids used in phosphorylation during post-translational modification
Ser
Thr
Tyr
amino acids used in hydroxylation during post-translational modification
pro
lys
methylation of histones
inhibits transcription
acetylation of histones
promotes transcription
lowers energy required for transition state (free energy of activation); increases rate of rxn
enzyme
rxn speed is increased dramatically when you introduce more ____
substrate
this alters enzyme activity and is different in different areas of the body
pH
extreme temperatures (high and low) do what to enzymes
inactivate them
substrate concentration at 1/2 vmax; similar to ligand concentration needed to occupy 50% of binding sites
Measure of AFFINITY
Km; Kd
rxn speed is proportional to substrate concentration
first order
independent of substrate concentration
zero order
drug that competes with HMG-CoA (substrate at the active site); more drug than substrate leads to enzyme activity reduced
statin
shift of curve to the right (Km increases-add more substrate to get back to Km)
competitive inhibition
inhibitor does not compete with substrate at binding site; amount of active enzyme has decreased (vmax decreases)
noncompetitive
example of noncompetitive inhibitor
lead
lead being a noncompetitive inhibitor of ferrochelatase impairs heme synthesis and leads to what
anemia
inhibitor only binds to enzyme-substrate complex; vmax and Km decrease
uncompetitive enzyme inhibition
example of uncompetitive inhibitor (immunosuppressant); inhibits IMP dehydrogenase (B and T cells use this process)
mycophenolate
similar to noncompetitive; vmax decreases and Km stays the same
irreversible inhibition
organophosphorus pesticides leads to inhibition of acetylcholinesterase= SLUDGEM
irreversible inhibition
(drug) proton pump inhibitor; type of irreversible inhibition
omeprazole
can change Vmax or Km
allosteric regulators
AMP, GMP, IMP are heterotropic what
allosteric inhibitors
if IMP, GMP, and AMP are abundant in the cell; what feedback happens
negative
how cells even out substrates and products
+ and - feedback loops
what reduces DNA synthesis and explains toxicity of increased levels of dATP in adenosine deaminase deficiency
binding of dATP to allosteric sites on enzyme inhibiting enzyme activity
all CK in the brain is what isoform
BB
all CK in skeletal muscle is what isoform
MM
in cardiac muscle, 1/3 of CK is ___ and the rest is_____
MB; MM
enzyme indicator that cardio conversion (after myocardial infarction) was successful
MB (returns to normal value-decreases)
antibiotic that binds at A site and acts as a peptidyl acceptor
puromycin
