Biochemistry- Molecular Flashcards
Heterochromatin
HeteroChromatin = Highly Condensed.
Barr bodies
Euchromatin
Eu = true, “truly transcribed.”
Euchromatin is Expressed
DNA methylation
CpG Methylation Makes DNA Mute.
Histone acetylation
Histone Acetylation makes DNA Active.
Purinas
PURines (A,G)—2 rings
PURe As Gold.
Pirimidinas
PYrimidines (C,U,T)—1 ring.
CUT the PY (pie).
NucleoSide
NucleoTide
base + (deoxy)ribose (Sugar).
base + (deoxy)ribose + phosphaTe;
Amino acids necessary for purine
synthesis:
GAG:
Glycine
Aspartate
Glutamine
Leflunomide
pyrimidine synthesis: inhibits dihydroorotate
dehydrogenase
Methotrexate (MTX), trimethoprim (TMP),
and pyrimethamine:
pyrimidine synthesis: inhibit dihydrofolate
reductase
5-fluorouracil (5-FU)
pyrimidine synthesis: inhibits thymidylate synthase
6-mercaptopurine (6-MP) and its prodrug
azathioprine:
inhibit de novo purine synthesis
Mycophenolate and ribavirin:
purine synthesis: inhibit inosine
monophosphate dehydrogenase
Hydroxyurea:
purine and pyrimidine synthesis: inhibits ribonucleotide
reductase
Adenosine deaminase
deficiency
dATP toxicity in lymphocytes. autosomal recessive
Lesch-Nyhan
syndrome
Defective purine salvage due to absent HGPRT HGPRT: Hyperuricemia Gout Pissed off (aggression, self-mutilation) Retardation (intellectual disability) DysTonia
Lesch-Nyhan
syndrome Treatment
allopurinol or febuxostat (2nd line).
Most amino acids are coded by multiple codons, Exceptions:
methionine and tryptophan encoded
by only 1 codon (AUG and UGG
Genetic code features
Unambiguous
Degenerate/redundant
Commaless, nonoverlapping
Universal
DNA replication is
semiconservative, involves both continuous and discontinuous (Okazaki fragment) synthesis, and
occurs in the 5′ 3′ direction
Origin of
replication A
AT-rich sequences (such as TATA box regions)
are found in promoters and origins of
replication.
Replication fork
Y-shaped region along DNA template where
leading and lagging strands are synthesized.
Helicase
Unwinds DNA template at replication fork.
Single-stranded
binding proteins
Prevent strands from reannealing.
DNA
topoisomerases
Create a single- or double-stranded break in the
helix to add or remove supercoils.
Irinotecan/topotecan
Etoposide/teniposide
Fluoroquinolones
- inhibit eukaryotic topoisomerase I.
- inhibit eukaryotic topoisomerase II.
- inhibit prokaryotic topoisomerase II (DNA gyrase) and topoisomerase IV.
Primase
Makes an RNA primer on which DNA
polymerase III can initiate replication.
DNA ligase
Joins Okazaki fragments
Telomerase
Eukaryotes only. An RNA-dependent DNA
polymerase that adds DNA to 3′ ends of
chromosomes to avoid loss of genetic material
with every duplication.
DNA polymerase III
DNA polymerase III has 5′ 3′ synthesis and
proofreads with 3′ 5′ exonuclease.
DNA polymerase I
Same functions as DNA polymerase III, also
excises RNA primer with 5′ 3′ exonuclease.
Mutations in DNA
silent «_space;missense < nonsense < frameshift.
Transition—
Transversion—
purine to purine (eg, A to G) or pyrimidine to pyrimidine (eg, C to T).
purine to pyrimidine (eg, A to T) or pyrimidine to purine (eg, C to G).
stop codon
(UAG, UAA, UGA)
splice site mutation
is a genetic mutation that inserts, deletes or changes a number of nucleotides in the specific site at which splicing takes place during the processing of precursor messenger RNA into mature messenger RNA
operón
una unidad genética funcional formada por un grupo o complejo de genes capaces de ejercer una regulación de su propia expresión por medio de los sustratos con los que interactúan las proteínas codificadas por sus genes.
DNA repair
Single strand
Nucleotide excision repair
Base excision repair
Mismatch repair
DNA repair
Double strand
Nonhomologous end joining
Lynch syndrome
(hereditary nonpolyposis colorectal cancer [HNPCC]).
Mismatch repair is defective
xeroderma pigmentosum
Defective Nucleotide excision repair prevents repair of pyrimidine dimers that are formed as a result of ultraviolet light exposure.
Defect in ataxia telangiectasia, breast/ovarian
cancers with BRCA1 mutation, and Fanconi
anemia.
Nonhomologous end joining
mRNA start codons
AUG inAUGurates protein synthesis. (methionine)
mRNA stop codons
UGA = U Go Away. UAA = U Are Away. UAG = U Are Gone.
Promoter
Site where RNA polymerase II and multiple
other transcription factors bind to DNA
Enhancer
Stretch of DNA that alters gene expression by
binding transcription factors
Silencer
Site where negative regulators (repressors) bind.
RNA polymerase I
RNA polymerase II
RNA polymerase III makes 5S rRNA, tRNA
(smallest RNA, tiny).
makes rRNA (most numerous RNA, rampant). makes mRNA (largest RNA, massive). mRNA is read 5′ to 3′. makes 5S rRNA, tRNA (smallest RNA, tiny).
I, II, and III
are numbered in the same order
that their products are used in protein
synthesis: rRNA, mRNA, then tRNA.
Actinomycin D
inhibits RNA polymerase in
both prokaryotes and eukaryotes.
α-amanitin, found in Amanita phalloides (death
cap mushrooms),
inhibits RNA polymerase II. severe hepatotoxicity if ingested.
Capped, tailed, and spliced transcript is called…
mRNA.
polyadenylation signal.
AAUAAA
Splicing of pre-mRNA
- Primary transcript combines with (snRNPs) form spliceosome.
- Lariat-shaped (looped) intermediate is
generated. - Lariat is released to precisely remove intron
and join 2 exons.
Antibodies to spliceosomal snRNPs (anti-
Smith antibodies)
highly specific for SLE
Anti-U1 RNP antibodies
highly associated with mixed connective tissue
disease (MCTD).
Introns vs exons
Introns are intervening sequences and stay
in the nucleus, whereas exons exit and are
expressed.
microRNAs
regulate gene expression by targeting the 3′ untranslated region of specific mRNAs for
degradation or translational repression
tRNA T-arm:
contains the TΨC (ribothymidine, pseudouridine, cytidine. T-arm Tethers tRNA molecule to ribosome.
tRNA D-arm:
contains dihydrouridine residues. D-arm Detects the tRNA by aminoacyl-tRNA synthetase.
tRNA structure
Have CCA at 3′ end along. The amino acid is covalently bound to the 3′ end of the tRNA. CCA: Can Carry Amino acids
Aminoacyl-tRNA synthetase
scrutinizes amino acid before and after it binds to tRNA. Is responsible for accuracy of amino acid selection.
Elongation
Think of “going APE”:
A site = incoming Aminoacyl-tRNA.
P site = accommodates growing Peptide.
E site = holds Empty tRNA as it Exits.
Ribosome
Eukaryotes:
PrOkaryotes:
40S + 60S 80S (Even).
30S + 50S 70S (Odd).
30S + 50S 70S (Odd).
Intracellular protein involved in facilitating and/or maintaining protein folding.
Covalent alterations
Phosphorylation, glycosylation, hydroxylation, methylation, acetylation, and ubiquitination.
wobble phenomenon.
different codons that can be created but they only code for 20 amino acids.
