Biochemistry Flashcards
what 2 amino acids are histones primarily made from?
lysine and arginine
which histrone protein is NOT part of the nucleosome core?
H1, this protein attaches to the linker DNA between the beads (nucleosomes)
differentiate heterochromatin and euchromatin
heterochromatin - highly condensed, transcriptionally inactive
euchromatin - less condensed, transcriptionally active
where does DNA typically get methylated? what is the result?
on CpG islands
it represses transcription at that location (“M”ethylation makes DNA “M”ute)
what is the result of histone methylation?
histone methylation also tends to repress transcription, however in a few instances it can actually activate it (histone “M”ethylation “M”ostly makes DNA “M”ute)
what is the result of histone acetylation?
histone acetylation relaxes the DNA coiling thus allowing for transcription (“A”cetylation “A”ctivates DNA)
how many rings are in purines? pyrimidines?
which bases are purines? pyrimidines?
purines - 2, A and G
pyrimidines - 1, C, T and U
how many H-bonds between G-C? A-T?
G-C = 3 H-bonds (therefore stronger/higher boiling point)
A-T = 2 H-bonds
name 3 amino acids needed for purine synthesis
“GAG” (consequently G and A are purines)
Glycine
Aspartate
Glutamine
differentiate nucleoSides and nucleoTides
nucleoTides have attached phosphate (via a 3’-5’ phosphodiester bond), nucleoSides do not
which DNA base contains a methyl group?
thymine (THYmine has a meTHYl)
what reaction and substrate is used to synthesize uracil?
deamination of cytosine
what are the steps for de novo purine syntheses?
- start with sugar and phosphate (PRPP)
2. add the DNA base
what are the steps for de novo pyrimidine syntheses?
- make a temporary base (orotic acid)
- add sugar and phosphate (PRPP)
- modify the base
in de novo nucleotide synthesis, which is made first, ribonucleotides of deoxynucleotides? what enzyme converts the first to the second?
1st is ribonucleotides
ribonucleotide reductase converts them to deoxy…
name two metabolic pathways the carbamoyl is used in
- urea cycle
2. de novo pyrimidine synthesis
name 10 drugs (anti-cancer and/or antibiotic) that work by interfering with nucleotide synthesis and how they do so (if you’re a badass)
- leflunomide (inhibits dihydroorotate dehydrogenase which makes orotic acid [for pyrimidines])
- mycophenolate (inhibits IMP dehydrogenase which makes GMP [for purines])
- ribavirin (same as #2)
- hydroxyurea (inhibits ribonucleotide reductase which makes deoxynucleotides [for pyrimidines])
- 6-mercaptopurine [6-MP] (inhibit ne dono purine synthesis)
- azathioprine (prodrug of #5, same function)
- 5-fluorouracil [5-FU] (inhibits thymidylate synthesis [for pyrimidines])
- methotrexate [MTX] (inhibit dihydrofolate reductase therefore making less dTMP needed for bacteria)
- trimethoprim (TMP) (same as #8)
- pyrimethamine (same as #8)
page 67 in the book
purine salvage deficiencies diagram (page 68)
don’t understand diagram…
how does adenosine deaminase deficiency cause pathology?
adenosine deaminase is mainly involved in the purine metabolism/salvage pathway. this pathway is heavily utilized by lymphocytes as their source of purines (mostly adenosine?). therefore, without purines for DNA synthesis the body can’t produce B or T cells. this is one of the major autosomal recessive caused of SCID
what is lesch-nyhan syndrome? what are they symptoms? what is its inheritance pattern? what is the treatment?
its a defect in the purine salvage pathway due to a deficiency in HGPRT (Hypoxanthine-Guanine PhosphoRibosylTransferase). it results in excessive uric acid production.
“HGPRT as a mnemonic for symptoms”
- Hyperuricemia
- Gout
- Pissed off (agression/self mutitation)
- Retardation
- dysTonia
X-linked recessive
treatment: allopurinol
explain what the 4 features of the genetic code mean:
- unambiguous
- degenerate/redundant
- commaless/nonoverlapping
- universal
- unambiguous - each codon only codes for ONE AA
- degenerate/redundant - most AAs are encoded by MULTIPLE codons (except MET and TRP)
- commaless/nonoverlapping - read continuously from a fixed starting point
- universal - the codes is conserved throughout evolution (except in mitochondria)
DNA replication stuff (page 69)
mostly skipped since I know the hell out of it
what is the mechanism of action of fluroquinolones?
they inhibit DNA gyrase (prokaryotic topoisomerase II) thus preventing bacterial DNA synthesis
what is the function of the following enzymes/proteins?
- single-stranded binding proteins
- primase
- DNA pol. I
- DNA pol. III
- single-stranded binding proteins - prevents DNA strands from rennealing
- primase - adds an RNA primer to the DNA for DNA pol. III to bind to
- DNA pol. III - elongates leading strand (5’ to 3’) and proofreads in the opposite direction
- DNA pol. I - same as pol. III except that is can also remove the RNA primer
(#3 and 4 are PROKARYOTES only)
differentiate transition and transversion in terms of DNA mutation
transition - purine to purine OR pryimidine to ptrimidine change
transversion - purine to pyrimidine OR vice versa
differentiate a missense vs. a nonsense mutation
missense - a NT substitution resulting in the change of base (ex. sickle cell disease)
nonsense - a NT substitution resulting in a premature stop codon
name 3 single strand DNA repair mechanisms and 1 double strand repair mechanism
SS:
1. NER (nucleotide excision repair) - removed damaged nucleotide as well as adjacent NTs and uses template to repair the spot
- BER (base excision repair) - removes a single base and replaces it with the correct one (useful in spontaneous/toxic deaminations)
- mismatch repair - recognizes and replaces missmatched NTs on a newly synthesized strand
DS:
1. non-homologous end joining - brings together two ends of DNA fragments (useful for DS breaks)
what is the cause of zeroderma pigmentosum?
a defect in nucleotide excision repair (NER), which prevents the repair of pyrimidine (thymine) dimers caused by UV light
what is the cause of hereditary nonpolyposis colorectal cancer (HNPCC)??
a defect in DNA mismatch repair
what is the cause of ataxia telangiectasia?
a defect in non homologous end joining (DS DNA break fixing)
what are the 3 stop codons?
UGA (U Go Away)
UAA (U Are Away)
UAG (U Are Gone)
differentiate DNA promoters, enhancers and silencers.
promoters - site where RNA pol. (and other TFs) binds [CAAT and TATA boxes]
enhancers - stretch of DNA that binds TFs which causes increased expression of the gene
silencers - stretch of DNA that binds TFs which causes decreased expression of the gene
what is the main function of the 3 eukaryotic RNA polymerases?
RNA pol. I - makes rRNA (the larger one)
RNA pol. II - makes mRNA
RNA pol. III - makes tRNA (and the small rRNA)
what are the 3 sites in a eukaryotic ribosome and what do they do?
“APE”
A site - accepts incoming Aminoacyl-tRNAs
P site - accommodates the growing Peptide
E site - Empties tRNA and Exits
which cell cycle checkpoints do the following tumor suppressor genes work at?
- p53
- RB
they BOTH work at the G1 to S checkpoint preventing it from proceeding if there is DNA damage
what is the cause and symptoms of li-fraumeni syndrome?
caused by a mutation in the p53 tumor suppressor gene. it leads to a susceptibility to developing cancer
what causes I-cell disease and what are some of the symptoms?
a defect of [a?] phosphotransferase in the golgi. this leads to the inability of the golgi to add mannose-6-phosphate to new proteins which is used as a targeting substituent for lysosomes. the result it that these proteins are excreted from the cell rather than moving to lysosomes.
symptoms:
- coarse facial features
- clouded corneas
- restricted joint movements
- high plasma levels of lysosome enzymes
- inclusion bodies
what is a signal recognition protein? what happens if they are deficient?
cytosolic ribonucleoproteins that traffic proteins from the ribosome to the RER. without them, proteins build up in the sytoplasm
what is the function of the following golgi trafficking proteins?
- COPI
- COPII
- clathrin
- COPI - retrograde transfer between two golgi sacs (from more plasma membrane side to more nuclear/deeper side)
- COPII - antergrade transfer between two golgi sacs
- clathrin - transfers between the trans-golgi (the plasma membrane side) to lysosomes or the plasma membrane
list the 3 functions of peroxosomes
catabolism of…:
- very-long-chain fatty acids
- branched chain fatty acids
- amino acids
what are dyneins and kinesins? what do they do?
they are molecular motor proteins that travel along microtubules.
- dyneins move from the + end (growing end) to the - end
- kinesins in the opposite direction
name 5 drugs that act on microtubules and what they’re used for
mnemonic: “Microtubules Get Constructed Very Poorly)
- Mebendazole (anti-helminthis)
- Griseofulvin (anti-fungal)
- Colchicine (anti-gout [and cancer?])
- Vincristine/Vinblastine (anti-cancer)
- Paclitaxel (anti-cancer)
what is kartagener syndrome? what causes it? what are some symptoms?
(AKA primary ciliary dyskinesia) is an immobility of cilia due to a defect in dynein (which, in addition to transporting proteins on MTs, can also cause cilia to move by linking adjacent doublets in the 9+2 MT arangment causing them to bend). this lease to immobility of cilia thus causeing:
- infertility in both men and women (sperm/uterin tubes)
- recurrent respiratory infections
- situs inversus (for some odd reason)
list the targeted cell type for the following immunohistochemical intermediate filament stains:
- Vimentin
- desmin
- cytoketatin
- GFAP
- neurofilaments
- Vimentin - connective tissue
- desMin - Muscle
- cytoketatin - epithelial cells
- GFAP - nueroglia (think reactive astrocytes)
- neurofilaments - neurons