Biochemistry Flashcards
Heterochromatin
Condensed, appears darker on EM. Transcriptionally inactive, sterically inaccessible.
HeteroChromatin = Highly Condensed. Barr bodies (inactive X chromosomes) are heterochromatin .
Euchromatin
Less condensed, appears lighter on EM. Transcriptionally active, sterically accessible.
Eu = true
“truly transcribed”
DNA methylation
Template strand cytosine and adenine are methylated in DNA replication, which allows mismatch repair enzymes to distinguish between old and new strands in prokaryotes
DNA methylation at CpG islands represses transcription.
CpG Methylation Makes DNA Mute
Histone methylation
Usually reversibly represses DNA transcription, but can activate it in some cases depending on methylation location.
Histone Methylation Mostly Makes DNA Mute.
Histone acetylation
Relaxes DNA coiling, allowing for transcription.
Histone Acetylation makes DNA Active.
NucleoSide
base + (deoxy)ribose (Sugar)
NucleoTide
base + (deoxy)ribose + phosphaTe
linked by 3’-5’ phosphodiester bond
PURines
2 rings
PURe As Gold
Adenine
Guanine
GAG - amino acids necessary for purine synthesis:
Glycine
Aspartate
Glutamine
PYrimidines
1 ring
CUT the PY (pie)
Cytosine, Uracil, Thymine (Thymine has a methyl)
Deamination of cytosine makes uracil
Uracil in RNA; Thymine in DNA
Hydrogen bonding between DNA bp
G-C bond (3 H bonds) stronger than A-T bond (2 H bonds).
Higher G-C content —> Higher melting temp of DNA
De novo synthesis
refers to the synthesis of complex molecules from simple molecules such as sugars and amino acids, as opposed to recycling after partial degradation
Ex: nucleotides are not needed in the diet as they can be constructed from small precursor molecules such as formate and aspartate.
Various immunosuppressive, antineoplastic, and antibiotic drugs function by interfering with nucleotide synthesis
Leflunomide
Disrupt pyrimidine synthesis
Inhibits dihydroorotate dehygrogenase
Methotrexate (MTX)
Disrupt pyrimidine synthesis
inhibit dihydrofolate reductase (decreases [dTMP]) in humans
Trimethoprim (TMP)
Disrupt pyrimidine synthesis
inhibit dihydrofolate reductase (decreases [dTMP]) in bacteria
Pyrimethamine
Disrupt pyrimidine synthesis
inhibit dihydrofolate reductase (decreases [dTMP]) in protozoa
5-fluorouracil (5-FU)
Disrupt pyrimidine synthesis
forms 5-F-dUMP, which inhibits thymidylate synthase (decreases dTMP)
dTMP = deoxythymidine monophosphate
6-mercaptopurine (6-MP) and its prodrug azathioprine
Disrupt purine synthesis
inhibit de novo purine synthesis
Mycophenolate
Disrupt purine synthesis
inhibit inosine monophosphate dehydrogenase
Ribavirin
Disrupt purine synthesis
inhibit inosine monophosphate dehydrogenase
Hydroxyurea
Disrupts purine and pyrimidine synthesis
inhibits ribonucleotide reductase
Adenosine deaminase deficiency
ADA is required for degradation of adenosine and deoxyadenosine.
In ADA deficiency,
increased dATP –> toxicity in lymphocytes
One of the major causes of autosomal recessive SCID
Lesch-Nyhan syndrome
Defective purine salvage due to absent HGPRT, which converts hypoxanthine to IMP and guanine to GMP. Results in excess uric acid production and de novo purine synthesis. X-linked recessive
Findings: intellectual disability, self-mutilation, aggression, hyperuricemia (orange “sand” [sodium urate crystals] in diaper), gout, dystonia.
HGPRT: Hyperuricemia Gout Pissed off (aggression, self-multilation) Retardation (intellectual disability) DysTonia
Unambigous
Genetic code features
Each codon specifies only 1 amino acid
Degenerate/redundant
Genetic code features
Most amino acids are coded by multiple codons
Exceptions: methionine and tryptophan encoded by only 1 codon (AUG and UGG, respectively)
Commaless, nonoverlapping
Genetic code features
Read from a fixed starting point as a continuous sequence of bases
Exceptions: some viruses
Universal
Genetic code features
Genetic code is conserved throughout evolution.
Exception in humans: mitochondria
DNA replication
Eukaryotic DNA replication is more complex than the prokaryotic process but uses many enzymes analogous to those listed below. In both prokaryotes and eukaryotes, DNA replication is semiconservative and involves both continuous and discontinous (Okazaki fragment) synthesis
Origin of replication
Particular consensus sequence of base pairs in genome where DNA replication begins.
May be single (prokaryotes) or multiple (eukaryotes)
AT-rich sequences are found in promoters and origins of replication
Replication fork
Y-shaped region along DNA template where leading and lagging strands are synthesized
Single-stranded binding proteins
Prevent strands from reannealing
Helicase
Unwinds DNA template at replication fork
DNA topoisomerases
Create a single- or double-stranded break in the helix to add or remove supercoils
Topoisomerase inhibitors:
fluoroquinolones - prokaryotic topoisomerase II [DNA
gyrase] and topoisomerase IV
etoposide/teniposide - eukaryotic topoisomerase II
Primase
Makes an RNA primer on which DNA polymerase III can initiate replicatii
