DNA bases and disease

Question 1

Histones

Answer 1

+ Charge, made of 2x(H2A, H2B, H3, H4) bound to DNA (- charge) by H1
DNA loops around each twice
Rich in arginine and lysine

Question 2

Heterochromatin

Answer 2

Condensed, dark, methylated

Barr body

Question 3

Euchromatin

Answer 3

Light, acetylated, expressed

Question 4

Methylation

Answer 4

On C and A in template strand in DNA replication
so MMR can tell difference
At CpG islands represses transcription

Question 5

Acetylation

Answer 5

Relaxes DNA on histones allows transcription room

Question 6

Nucleoside

Answer 6

Base and a sugar (deoxy)ribose

Question 7

Nucelotide

Answer 7

Base and a sugar (deoxy)ribose + phosphate linked by 3’-5’ phosphodiester bond

Question 8

Purines

Answer 8

A, G

2 Rings

Question 9

Pyramidines

Answer 9

C, U, T

1 Ring

Question 10

Methylated base

Answer 10

T

Question 11

Stronger base pair

Answer 11

C-G (preponderance raises melting point)

Question 12

Deamination reactions

Answer 12

A to G;

C to U

Question 13

Demethyated T

Answer 13

U

Question 14

Amino acids needed to make purines

Answer 14

Glycine, aspartate, glutamine

Question 15

Purine base production (de novo/salvage)

Answer 15

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

Question 16

Pyramidine base prduction

Answer 16

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!

Question 17

Leflunomide

Answer 17

Inhibits dihydroorotate dehydrogenase (pyrimadine)

Question 18

Methotrexate

Answer 18

Inhibit DHFR so less dTMP in humans

Question 19

Trimethoprim

Answer 19

Inhibit DHFR so less dTMP in bacteria

Question 20

Pyrimethamine

Answer 20

Inhibit DHFR so less dTMP in protozoa

Question 21

5-FU

Answer 21

Inhibits thymidylate synthase

so less dTMP

Question 22

6-MP and azothioprine (prodrug)

Answer 22

inhibit de novo purine synth

Question 23

Mycophenylate, ribivarin

Answer 23

Inhibit IMP Dehydrogenase so no GMP

Question 24

Hydroxyurea

Answer 24

Inhibits RNR

Question 25

Adenoside deaminase deficiency

Answer 25

AR cause of SCID because increased dATP is cytotoxic to lymphocytes

Question 26

Lesch-Nyhan syndrome

Answer 26

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