DNA bases and disease Flashcards
Histones
+ Charge, made of 2x(H2A, H2B, H3, H4) bound to DNA (- charge) by H1
DNA loops around each twice
Rich in arginine and lysine
Heterochromatin
Condensed, dark, methylated
Barr body
Euchromatin
Light, acetylated, expressed
Methylation
On C and A in template strand in DNA replication
so MMR can tell difference
At CpG islands represses transcription
Acetylation
Relaxes DNA on histones allows transcription room
Nucleoside
Base and a sugar (deoxy)ribose
Nucelotide
Base and a sugar (deoxy)ribose + phosphate linked by 3’-5’ phosphodiester bond
Purines
A, G
2 Rings
Pyramidines
C, U, T
1 Ring
Methylated base
T
Stronger base pair
C-G (preponderance raises melting point)
Deamination reactions
A to G;
C to U
Demethyated T
U
Amino acids needed to make purines
Glycine, aspartate, glutamine
Purine base production (de novo/salvage)
Requires apartate, glycine, glutamine, and THF
Substrate = Ribose5P
Converted to PRPP (phosphoribosyl pyrophospatase) by PRPP Synthase
Multistep process converts PRPP to IMP
IMP then goes on to form AMP and GMP
Pyramidine base prduction
Requires aspartate
Substrate = Glutamine and 2CO2
Uses 2ATP with carbamoyl phosphate synthase II to generate 2ADP + Pi + Glutamate and CARBAMOYL PHOSPHATE
CP then combines with aspartate to make OROTIC ACID
OA combines with PRPP from purine synth. pathway to make UMP
UMP to CTP
or with ribonucleotide reductase to dUDP
phosphatase to dUMP
dUMP to dTMP using thymidylate synthase and DHFR system!
Leflunomide
Inhibits dihydroorotate dehydrogenase (pyrimadine)
Methotrexate
Inhibit DHFR so less dTMP in humans
Trimethoprim
Inhibit DHFR so less dTMP in bacteria
Pyrimethamine
Inhibit DHFR so less dTMP in protozoa
5-FU
Inhibits thymidylate synthase
so less dTMP
6-MP and azothioprine (prodrug)
inhibit de novo purine synth
Mycophenylate, ribivarin
Inhibit IMP Dehydrogenase so no GMP
Hydroxyurea
Inhibits RNR
Adenoside deaminase deficiency
AR cause of SCID because increased dATP is cytotoxic to lymphocytes
Lesch-Nyhan syndrome
Defective purine salvage due to HGPRT, high HX and Guanine, low IMP/GMP
Excess uric acid and de novo purine synth.
XLR
Intellectual disability, self-mutilation, aggression, hyperuricemia, orange sand in diaper, gout, dystonia
Tx: 2nd line XOIs
