Biochemistry: Molecular Flashcards
Chromatin structure
Heterochromatin DNA that is looped around a histone octamer to form a nucleosome “beads on a string” formation
Phosphate groups on the DNA = (-) charge
Lysine and arginine AAs on histone = (+) charge
note this structure is for all chromatin DNA that is NOT mitochondrial DNA. Mitochondrial DNA is circular and does not warp around histones
Heterochromatin
Condensed from of chromatin that is functional inactive (cant be transcribed)
Is darker on EM since it is denser
High levels of methylation ; low levels of acetylation
Barr bodies
Inactive X chromosomes that may appear on the nucleus of heterochromatin DNA
Euchromatin
Less condensed version fo chromatin DNA. Able to be transcribed
Is lighter on EM
DNA methylation
Act of adding a methyl group to DNA segment ends.
Does not change the DNA sequence at all, but makes the whole sequence “silenced” or not able to be transcribed.
- commonly seen as a natural part of the following:
- aging
- exposure to carcinogens
- genomic imprinting
- inactivation fo X chromosomes*
Histone methylation
Adds a methyl group to histones, provide an almost complete (90%) “silence” of the wrapped heterochromatin.
- some of the heterochromatin can still unpackage and become euchromatin and be transcribed, but its very little
Histone acetylation
Addition of Acetyl groups tot he histone, causing all heterochromatin to unpackage and become euchromatin
- increases transcription
removes the histones (+) charge via adding the acetyl groups to lysine and arginine AAs
Histone deaceytlation
Removal of acetyl groups, causes packaging of euchromatin into heterochromatin around the histones
makes lysine and arginine AAs (+) again
Nucleoside vs nucleotide
NucleoSide = base + deoxyribose (Sugar ONLY)
NucleoTide = base + Deoxyribose + phosphaTe group w/ 3’5 bonds
Purines vs Pyrimidines
Purines = 2 rings
- A/G
- “Pure as gold” (AG)
Pyrimidines = 1 ring
- C/T/U
- “CUT the PY”
Deamination reactions of the purines and pyrimidines
Cytosine -> uracil
Uracil -> thymine
Adenine -> hypoxanthine
Guanine - > xanthine
Amino acids needed for purine synthesis
Glycine
Aspartate
Glutamine
“Cats purrine until the GAG”
H bonds and respect to melting point temps
C-G bonds = 3 H
A- T bonds = 2 H
More H bonds = high melting point
What drugs affect pyrimidine synthesis only?
Leflunomide: inhibits dihydroorotate dehydrognease
- aspartate + phosphate -> orotic acid
5-Fluorouracil (5-FU) & capecitabine: inhibts thymidylate synthase
- dUMP -> dTMP
What drugs affect purine synthesis only?
6-mercaptopurine (6-MP) & azathioprine: inhibit the whole thing
Mycophenolate & ribavirin: inhibit Inosine monophosphate dehydrogenase
- IMP -> GMP
What Drugs that affect both purine and pyrimidine synthesis?
Hydroxyurea: inhibits ribonucleotide reductase
Methotrexate (MTX), and trimethoprim (TMP): inhibit dihydrofolate reductase in humans and material respectively
- MTX = autoimmune and cancer ; TMP= antibiotic
Leach-Nyhan syndrome
X-linked recessive Genetic disorder where there is absent HGPRT enzymes
- cant convert hypoxanthine -> IMP and guanine -> GMP
- results in over production of uric acid
Symptoms H: hyperuricemia G: Gout P: Pissed off (increased aggression and thoughts of self mutilation) R: Retardation T: DysTonia
Treatment:
- Allopurinol (1st line)
- feuxostat (2nd line)
- both are Xanthine oxidase inhibtors*
4 Genetic code features
1) Unambiguous
2) degenerate/redundant
- “wobble” codons exist meaning that codons that have the same first 2 letters, but different 3rd letter can encode for the same AA
- exception is met (AUG) and Tryptophan (UGG). These can only be made from these specific 3 letters
3) no overlapping
- codons are read from a fixed point and continuous sequence
4) universal
- is conserved throughout evolution
- exception is mitochondrial DNA
Telomerase effect on DNA replication
Found in eukaryotes only
Adds a DNA “cap” ( TTAGGG) to the 3’ end of chromosomes to prevent degradation with each duplication
- this is a common dysregulated cells in cancer*
Mutations ranked in order of damage
1) frame shift
- deletion or insertion fo a nulceotide(s) not divisible by 3
- causes a “shift” in the entire sequence
2) nonsense mutation
3) missense mutation
- changing one purine or pyrimidine to change 1 codon to signal for 1 different AA only
4) silent mutation
Lac operon
Classic example of a prokaryote operon response to environmental change
In the presence of high glucose and no lactose = NO transcription
- repressor protein is bound
- adenylate Cyclase is antagonized 100%
In the presence of low glucose and no lactose = mild transcription
- adenylate Cyclase is no longer antagonized - > increases cAMP -> binds CAP protein to operon and transcribes little amounts of DNA
- repressor protein is still bound though
In the presence of low glucose and lactose = high transcription
- adenylate Cyclase is no longer antagonized - > increases cAMP -> binds CAP protein to operon and transcribes lots of DNA
- repressor protein is no longer bound (lactose represses the repressor)
Types of RNA polymerases in eukaryotes
RNA 1 poly:
- makes rRNA (“rampant RNA” most common type)
- only present in nucleolus
RNA 2 poly:
- makes mRNA, MiRNA, and snRNA
- present everywhere
- a-amanitin inhibts RNA 2 poly
RNA 3 poly:
- makes tRNA
- present everywhere
RNA polymerases in prokaryotes
RNA 1 poly in prokaryotes makes all RNA types
- Rifampin is the antibiotic that blocks RNA poly in prokaryotes*
Exons vs introns
Exons:
- contain actual protein coding information
- are substituted in and out for specific proteins “alternative splicing”
Introns:
- contain gene expression information
- are always removed in forming mRNA
TRNA structure and function
T-arm = tethers the tRNA molecule to a ribosome
- required for binding
D-arm = allows for Detection of tRNA by a specific AA and vise versa
- allows for the proper AA to bind
- “charges” the tRNA
Function = carry amino acids to ribosomes
a mischarged tRNA reads the codon from mRNA properly, but binds the wrong AA to the codon
What are possible covalent modifications to a novel protein?
Phosphorylation
Glycosylation
Hydroxylation
Methylation
Acetylation
Ubiquitination
Ribosomal subunits for eukaryotes and prokaryotes
Eukaryotes
- 40s+ 60s = 80s
- all are EVEN
Prokaryotes
- 30s + 50s = 70s
- all are ODD
Elongation phase of protein synthesis
“APE”
A site = incoming amino Aminoacyl-tRNA binds to A site
P site = rRNA catalyzes peptide bond between already present AA and new AA to form a poly peptide. The polypeptide is moved to the tRNA in the P site
E site = peptidyl t-RNA (tRNA without an AA) is moved from P -> E site and exits the ribosome
Cell types based on cell cycles
Permanent cells:
- cells that remain in G0 phase (arrest phase) permanently
- least affected by chemo
- neurons. Skeet always and cardiac muscle cells, RBCs
Stable (quiescent) cells:
- cells that are in G0 phase but can enter G1 phase of mitosis if stimulated
- hepatocytes, lymphocytes, PCT, periosteal cells
Labile cells:
- cells that never go into G0 (arrest) phase
- most affected by chemo
- bone marrow, gut epithelium, skin, hair follicles
