BIOCHEMISTRY Flashcards
Chromatin Structure to fit into the nucleus
Beads on a string. Histone octamer to form a nucleosome
Gives positive and negative charges to DNA respectively
Phosphate (-) and Lysine and Arginine (+)
Does mitochondria utilize histones?
No. They have their own which is circular
Condensed, Transcriptionally inactive
Heterochromatin
Example of heterochromatin
Barr Bodies
Phase where DNA and histone synthesis occur?
S phase
Less condensed chromatin, transcriptionally active, sterically accessible
Euchromatin
Changes the expression of DNA segment without changing the sequence. Involved in genomic imprinting, x-chromosome inactivation, repression of transposable elements, aging, and carcinogenesis
DNA methylation
Within what gene promoter region does methylation repress gene transcription?
CpG
Usually causes reversible transcriptional suppression, but can also cause activation depending on location of methyl groups.
Histone methylation. (Histone Methylation Mostly Makes DNA Mute.
Allows transcription and relaxes DNA coiling.
Histone Acetylation
Components of nucleoside
Base + Deoxyribose (sugar)
Components of Nucleotide
Base + Deoxyribose + phosphate
Linkage of both nucleoside and nucleotide
3’-5’ phosphodiester bond
Number of rings for purine and pyrimidine respectively
2 and 1
Deamination of cytosine will form?
Uracil
Deamination of adenine will form?
Hypoxanthine
Deamination of guanine will form?
Xanthine
Deamination of 5-methylcytosine will form?
Thymine
Methylation of uracil makes what?
Thymine
Of the two base pair bonds, A-T and G-C, which is stronger?
G-C (3>2), higher G-C content, higher melting temperature of DNA.
Amino acids necessary for purine synthesis.
Glycine, Aspartate, Glutamine
Inhibits both purine and pyrimidine synthesis by inhibiting ribonucleotide reductase
Hydroxyurea
Inhibits purine synthesis by inhibiting de novo purine synthesis. Give its prodrug form also.
6-MP, 6-Mercaptourine (azathioprine)
Inhibit purine synthesis by inhibiting inosine monophosphate dehydrogenase.
Mycophenolate and ribavirin
Inhibits pyrimidine synthesis by inhibiting dihydroorotate dehydrogenase
Leflunomide
Inhibits drihydrofolate reductase (lower deoxythymidine monophosphate/dTMP in humans, bacteria, and protozoa respectively
Methotrexate (MTX), Trimethoprim (TMP), pyrimethamine
Where does CPS 1 usually occur?
Mitochondria (urea cycle)
Where does CPS2 occur?
Cytosol
Enzyme deficiency that is One of the major causes of autosomal recessive SCID. Higher dATP may cause lymphotoxicity.
Adenosine deaminase deficiency (ADA is required for degradation of adenosine and deoxyadenosine)
Enzyme deficiency due to 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
Lesch-Nyhan Syndrome
Common findings of Lesch-Nyhan Syndrome
Hyperuricemia Gout Pissed off(aggression, self-mutilation) Retardation (intellectual disability) Dystonia
Clinical feature of hyperuricemia in the laboratory
Orange sand (sodium urate crystals) in diaper
Treatment for Lesch-Nyhan Syndrome
Allopurinol or febuxostat
Genetic code feature where each codon specifies only 1 amino acid
Unambiguous
Genetic code feature where most amino acids are coded by multiple codons.
Degenerate/redundant
Codons that differ in 3rd position may code for the same tRNA/amino acid. Specific base pairing is usually required only in the first 2 nucleotide positions of mRNA codon
Wobble/Wobble theory
Genetic code feature where the DNA is read from a fixed starting point as a continuous sequence of bases
Commaless, nonoverlapping (except in some viruses)
Genetic code features where the genetic code is conserved throughout evolution (except in humans-mitochondria)
Universal
Semiconservative, involves both continuous and discontinuous (Okazaki fragments) synthesis and occurs in 5’-3’ direction
Eukaryotic DNA replication
Particular consensus sequence of base pairs in genome where DNA replication begins. May be single (prokaryotes) or multiple (eukaryotes)
Origin of replication
Found in promotors and origins of replication
AT-rich sequences (TATA box regions)
Y-shaped region along DNA template where leading and lagging strands are synthesized
Replication form
Unwinds DNA template at replication fork
Helicase
Prevents strands from reannealing
Single-stranded binding proteins
Create a single- or double-stranded break in the helix to add or remove supercoils
DNA topoisomerase
Makes an RNA primer on which DNA polymerase III can initiate replication
Primase
In eukaryotes: _________ inhibit topoisomerase I, while _______ inhibit topoisomerase II
Irinotecan/topotecan
Etoposide/teniposide
In prokaryotes, _______ inhibit TOP II (DNA gyrase) and TOP IV
Fluoroquinolones
Used by prokaryotes only. Elongates leading strand by adding deoxynucleotides to the 3’ end. Elongates lagging strand until it reaches primer of preceding fragment
DNA polymerase III
Proofreads each added nucleotide
3’-5’ exonuclease
Drugs blocking DNA replication often have a _______ thereby preventing addition of the next nucleotide (“chain termination”h
Modified 3’OH
Prokaryotic only. Degrades RNA primer; replaces it with DNA. Same functions as DNA polymerase III, also excises RNA primer with 5’-3’ exonuclease
DNA polymerase I
Catalyzes the formation of a phosphodiester bond within a strand of double-stranded DNA (joins Okazaki fragments)
DNA ligase
Eukaryotes only. A reverse transcriptase (RNA-dependent DNA polymerase) that adds DNA TO 3’ ends of chromosomes to avoid loss of genetic material with every duplication
Telomerase
Sequence of telomerase
TTAGGG
Purine-purine or pyrimidine-pyrimidine
Transition
Purine-pyrimidine or pyrimidine-purine
Transversion
Nucleotide substitution but codes for same/synonymous amino acid; often base change in 3rd position of codon (tRNA wobble)
Silent Mutation
Nucleotide substitution resulting in changed amino acid (conservative if new amino acid is similar in chemical structure). Ex. Sickle cell disease (substitution of glutamic acid with valine)
Missense mutation
Nucleotide substitution resulting in early stop codon (UAA, UAG, UGA). Usually results in non-functional protein
Nonsense mutation
Deletion or insertion of a number of a number of nucleotides not divisible by 3, resulting in misreading of all nucleotides downstream. Function may be disrupted or altered. Ex. (Duchenne muscular dystrophy, Tay-Sachs disease)
Frameshift mutation
Retained intron in the mRNA; protein with impaired or altered function. Rare cause of cancers, dementia, epilepsy, some types of B-thalassemia
Splice site mutation
Classic example of genetic response to an environmental change. Seen in the activity of E.coli in culture. Low glucose-high adenylate cyclase activity-high generation of cAMP from ATP- activation of catabolite activator protein (CAP)- increased transcription. High lactose-unbinds repressor protein from repressor/operator site-increased transcription
Lac operon gene activation