Biochemistry USMLE step 1
histones are rich in which 2 AA's (Ans- lysine & argenine
Barr bodies (what, type of chromatin) (Ans- inactive X chromosomes heterochromatin (highly condensed, sterically inaccessible)
less condensed, transcriptionally active, sterically accessible chromatin (Ans- euchromatin
DNA methylation at CpG islands (Ans- represses transcription
"CpG Methylation makes DNA Mute"
DNA methylation (what is methylated and why?) (Ans- template strand cytosine and adenine are methylated during replication --> mismatch repair enzymes can distinguish between old and new strands
Histone methylation (Ans- usually reversibly represses DNA transcription (can activate depending on location)
"histone Methylation Mostly makes DNA Mute"
Histone acetylation (Ans- relaxes DNA coiling --> permits transcription
"histone Acetylation makes DNA Active"
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function of methylation and acetylation (Ans- change DNA transcription activity
methylation mutes acetylation activates
purines (which, ring number) (Ans- A, G
- rings
PUR As Gold
pyrimidines (which, ring number) (Ans-
C, T, U
- ring
CUT the PY (pie is a single circle)
thymine vs uracil (Ans- thymine has a methyl, found in DNA deamination of cytosine --> uracil, found in RNA
base pair with 3 H-H bonds (and consequences) (Ans- G-C
G-C is stronger than A-T (2 H-H)
inc G-C content --> inc melting temperature of DNA
amino acids necessary for purine synthesis (Ans- GAG + THF
glycine aspartate 2 / 4
glutamine
nucleoside vs. nucleotide vs. nucleotide di/triphosphate (Ans- nucleoside = base + sugar nucleotide = base + sugar + phosphate nucleotide diphosphate = base + sugar + 2P's nucleotide triphosphate = base + sugar + 3P's
de novo purine synthesis (Ans- R5P --> PRPP by PRPP synthetase (adds 2P's) add base (hypoxanthine) --> IMP by HGPRT IMP converted to AMP and GMP
ribonucleotides --> deoxyribonucleotides (Ans- ribonucleotide reductase
carbamoyl phosphate involved in which 2 metabolic pathways?(Ans- de novo pyrimidine synthesis (CP synthetase II) urea cycle
de novo pyrimidine synthesis (Ans-
*Make temporary base:*
- glutamine + CO2 + ATP --> carbamoyl phosphate by CP synthetase II
- carbamoyl phosphate + aspartate --> orotic acid via dihydroorotate
dehydrogenase
*Add sugar + P (PRPP):*
- orotic acid + PRPP --> UMP --> UDP
*Modify base* 4a. UDP --> CTP 4b. UDP --> dUDP by ribonucleotide reductase
- dUDP --> dUMP 3 / 4
- dUMP + THF --> dTMP by thymidylate synthase = methylates uracil into
thymadine *THF (which becomes DHF) regenerated by dihydrofolate reductase
differences in de novo purine and pyrimidine synthesis
(Ans- purines: start with sugar + phos (PRPP), add base
pyrimidines: make temporary base (orotic acid), add sugar + phos (PRPP),
modify base (requires THF for thymidylate synthase)
inhibits dihydroorotate dehydrogenase
(Ans- leflunomide (tx: RA)
prevents carbamoyl phosphate --> orotic acid in pyrimidine synthesis
inhibits IMP dehydrogenase
(Ans- mycophenolate (tx: organ transplant rejection)
ribavirin (tx: viral infx)
prevents IMP --> GMP in purine synthesis
inhibits ribonucleotide reductase
(Ans- hydroxyurea (tx: SC dz > inc HbF)
prevents UDP --> dUDP (RNA > DNA) in pyrimidine synthesis
prodrug of 6-mercaptopurine (6-MP) (Ans- Azathioprine
MOA of 6-MP and Azathioprine (and use) (Ans- inhibit de novo purine synthesis
tx: leukemia, immune dzs (RA, IBD)
prevents PRPP --> IMP
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