Glossary of molecular biology: nucleic acids
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- adenine
-
adenine
- guanine
-
guanine
- cytosine
-
cytosine
- thymine
-
thymine
- uracil
-
uracil
- purine glycosidic bond
- b/w N-9 of ring and 1'C of sugar
- pyrimidine glycosidic bond
- b/w N-1 of ring and 1'C of sugar
- nucleases
- cut phosphodiester bonds
- exonucleases
- remove terminal nucleotides only
- endonucleases
- cut b/w internal nucleotides
- secondary structure of DNA, sometimes RNA
- double helix
can form b/w any ANTIPARALLEL and COMPLEMENTARY sequences:
1) dsDNA
2) inverted complementary sequences within RNA
3) RNA + DNA
- ds strands held together by
- 1) H bonds
2) base stacking
- H bonds b/w base pairs
- A-T/T-U: 2 H bonds
G-C: 3 H bonds (more stable)
- base stacking
- rings stacked over one another in interior of double helix
hydrophobic interactions add stability
- intercalating agents
- slide b/w neighboring base pairs in DNA
DNA can't be good template --> inhibits replication + transcription
ex: actinomycin D
- replication
- DNA to DNA
- transcription
- DNA to RNA
- translation
- RNA to proteins
- denaturation
- disrupts H bonds and hydrophobic but not covalent bonds
separates 2 strands
- A-T rich sequences
- usually found where DNA replication or RNA transcription initiates, since 2 strands must separate
- NaOH + DNA
- denatures 2/2 pH change
ionizes protons in H-N of base rings --> disrupts H bonds
- temp + DNA
- denatured over 80-90 deg C
- chemicals + DNA
- formamide + urea both denature DNA by interfering with H-bonds
- most DNA structure
- R-handed antiparallel helix
- conformations of linear DNA
- B DNA
Z DNA
A DNA
- B DNA
- most common
classic R-handed antiparallel helix with bases stacked on top of one another perpendicular to axis of helix
helix contains 2 grooves (major + minor) = where DNA-protein interactions occur
10.5 bp/turn
- Z DNA
- rare
found in sequences that are 1) G-C rich or 2) have long tracts of alternating purines & pyrimidines
L-handed antiparallel helix
occurs occasionally within B DNA chromosome
- A DNA
- anhydrous form of B DNA
R-handed antiparallel helix
bases not perfectly perpendicular to axis (20deg tilt)
found in RNA-DNA hybrids
- circular DNA
- found in mitochondrial DNA, most prok DNA, some viral DNA
can be relaxed or compacted by supercoils
no ends, therefore resistant to exonucleases
- topoisomerases
- relieve tension in supercoils of replicating DNA
make transient breaks (cut + reseal phosphodiester bonds) in DNA strands
- deoxynucleotide synthesis inhibitors
- used as antineoplastic agents
- 5-fluorouracil
- inhibits thymidylate synthetase
- hydroxyurea
- inhibits ribonucleotide reductase
- nucleotide degradation
- phosphate group and pentose removed
amino groups attached to ring(s) removed as ammonia by adenosine deaminase + glutamine deaminase
- purine degradation
- purine ring can't open so just make it soluble as possible so it can be excreted
- end product of purine degradation
- uric acid
- pyrimidine degradation
- pyrimidine ring can be opened and partially degraded
- thymidine degraded to
- butyrate
- uracil + cytosine degraded to
- beta-alanine
- purine/pyrimidine metabolism defects
- esp. in purine degradation
1) Gout
2) Lesch-Nyhan syndrome
3) SCID
- gout
- excess uric acid production
precipitates in joints --> inflammation
kidney dz 2/2 accumulation of uric acid in tubules
mostly in men
- elevated uric acid causes
- gout
2ndary to disorder with high NA turnover (polycythemia, leukemia)
- gout tx
- allopurinol = xanthine oxidase inhibitor
- xanthine oxidase
- catalyzes sequential oxidation of hypoxanthine to xanthine to uric acid
- lesch-nyhan syndrome
- deficiency in enzyme hypoxanthine-guanine phosphoribosyl transferase (HGPRT)
results in inability to recycle purines + overproduction of uric acid
- lesch-nyhan sx
- MR
hyperuricemia
gout
compulsive self-destructive behaviors
- ADA-deficient SCID
- adenosine deaminase (purine salvage pathway) deficiency --> defective B + T cell development
dATP accumulates in RBCs, which allosterically inhibits ribonucleotide reductase (required for DNA synthesis
must live in sterile environment