Biochemistry - Molecular

Question 1

chromatin structure - overview

Answer 1

*DNA exists in the condensed chromatin form to fit into the nucleus; DNA loops 2x around histone octamer to form a nucleosome
*H1 binds to nucleosome and to linker DNA, stabilizing the chromatin fiber
*DNA has a NEGATIVE charge from phosphate groups
*histones are LARGe and have POSITIVE charge from Lysine and ARGinine

Question 2

heterochromatin

Answer 2

*condensed DNA
*sterically inaccessible, thus transcriptionally INACTIVE
*increased methylation, decreased acetylation

Question 3

euchromatin

Answer 3

*less condensed DNA
*transcriptionally ACTIVE, sterically accessible
*Euchromatin is Expressed

Question 4

DNA methylation

Answer 4

*reversibly changes the expression of a DNA segment (without changing its sequence)
*methylation within DNA promoter (CpG islands) typically REPRESSES (silences) gene transcription

Question 5

histone methylation

Answer 5

*usually causes reversible SUPPRESSION of transcription
*lysine and arginine residues of histones can be methylated

Question 6

histone acetylation

Answer 6

*removal of a histone’s positive charge → relaxed DNA coiling → INCREASED transcription

Question 7

histone deacetylation

Answer 7

*removal of acetyl groups → tightened DNA coiling → DECREASED transcription

Question 8

de novo purine synthesis pathway

Answer 8

1. starts with ribose phosphate from HMP shunt
2. convert ribose-5-P to PRPP
3. convert PRPP to inosine monophosphate
4. convert IMP to AMP and GMP
   *note - requires aspartate, glycine, glutamine, and tetrahydrofolate
   *rate-limiting enzyme = glutamine-PRPP amidotransferase

Question 9

drugs that affect purine synthesis: ribavirin & mycophenolate

Answer 9

*inhibit IMP dehydrogenase → blocks conversion of IMP to GMP → inhibits synthesis of guanine nucleotides
*ribavirin is an antiviral; mycophenolate is an immunosuppressant

Question 10

drugs that affect purine synthesis: 6-mercaptopurine (6-MP) and azathioprine

Answer 10

*inhibit de novo purine synthesis (guanine phosphoribosyltransferase) → decreased IMP, AMP, and GMP
*mimics hypoxanthine/guanine
*CAUTION WITH ALLOPURINOL

Question 11

purine salvage

Answer 11

*salvages bases: adenine, guanine, and hypoxanthine
*converts back into nucleotides: AMP, GMP, and IMP
*requires PRPP
HGPRT enzyme (hypoxanthine-guanine phosphoribosyltransferase)** salvages hypoxanthine and guanine
**APRT (adenine phosphoribosyltransferase) salvages adenine

Question 12

purine breakdown

Answer 12

*hypoxanthine and guanine are converted into xanthine (by xanthine oxidase or guanase, respectively), which is the converted (by xanthine oxidase) into URIC ACID

Question 13

adenosine deaminase deficiency

Answer 13

*ADA is required for degradation of adenosine and deoxyadenosine
*ADA → increased dATP → decreased ribonucleotide reductase activity → decreased DNA precursors in cells → decreased lymphocytes
*one of the major causes of autosomal recessive SCID

Question 14

Lesch-Nyhan Syndrome

Answer 14

*X-linked absence of HGPRT
*excess uric acid production (“juvenile gout”)
*excess de novo purine synthesis (increased PRPP and IMP)
*clinical findings: intellectual disability, self-mutilation, aggression, hyperuricemia, gout, dystonia, macrocytosis
*treatment: allopurinol, febuxostat