Biochemistry Flashcards
Function of SER?
Steroid and phospholipid biosynthesis (adrenals, gonads, liver); detoxification (liver); sarcoplasmic reticulum in muscles
dTMP de-novo production
Catalyzed by thymidylate synthetase; 5,10-methyleneTHF + dUMP -> dihydrofolate + dTMP (dihydrofolate reductase)
Thalassemia intermedia
Associated with mutation 3 bases upstream from AUG in Kozak; Hypochromic, microcytic anemia
4 Types of Blots - detect what and probe?
Northern - RNA detection; ssDNA or RNA probe
Western - protein; Ab probe
Southern - DNA; ssDNA or RNA probe
Southwestern - DNA-binding protein; dsDNA
SNoW, DRoP
Which histone is not in the nucleosome core?
H1, which binds to nucleosome and linker DNA
Nucleosome characteristics?
Neg-charged DNA looped TWICE around histone OCTOMER (H2A, H2B, H3, H4)
Heterochromatin vs. euchromatin?
HeteroChromatin = Highly condensed Euchromatin = true; transcriptionally active
Three major epigenetic mechanisms
DNA methylation of CpG islands represses transcriptions; histone methylation mostly represses; histone acetylation relaxes DNA coiling and makes DNA more active
Difference between uracil and thymine?
Thymine has methyl group
AA’s necessary for purine synthesis
GAG - Glycine, Aspartate, Glutamine
Nucleoside v. nucleotide
Side = sugar + base; Tide = Sugar + base + phosphate
de novo purine synthesis how?
Ribose 5-P -> PRPP (PRPP synthase)
—> pathway (PRPP glutamyl amidotransferase = committed)
IMP —> AMP or GMP
What drugs affect purine synthesis and where?
6-MP at PRPP amidotransferase; Mycophenolate, ribavarin at IMP -> GMP (IMP dehydrogenase); drugs affecting folate
What enzyme makes deoxyribunucleotides?
Ribonucleotide reductase;
de novo pyrimidine synthesis?
Glutamine, CO2, ATP -> Carbamoyl phosphate
+ asparatet -> Orotic acid
+ PRPP -> UMP -> UDP -> dUDP -> dUMP -> dTMP
Orotic aciduria mutation?
UMP synthase (= orotate phosphoribosyl transferase + OMP decarboxylase) mutation; megaloblastic anemia, lethargy, weakness, growth retardation; treated with uridine –> salvage pathway to make UMP, which inhibits CPS-II to dec. orotic acid production
What are the two major targeted enzymes involved in the creation of dTMP?
Made from dUMP via thymidylate synthase, which requires N5N10-methylene THF, which requires Dihydrofolate reductase
What drugs target dTMP synthesis?
5-FU targets thymidylate synthase; MTX, TMP, pyrimethamine target dihydrofolate reductase
Hydroxyurea acts on what enzyme?
Ribonucleotide reductase (the enzyme that makes deoxyribonucleotides; in particular the UDP -> dUDP version)
Two major enzymes of purine salvage pathway?
HGPRT - Guanine -> GMP; Hypoxanthine -> IMP
APRT - Adenine -> AMP
Major cause of AR SCID?
Adenosine deaminase deficiency: leads to increased dATP -| ribonucleotide reductase -> prevention of DNA synthesis -> dec. lymphocyte count
Lesch Nyhan?
Absent HGPRT -> guanine and hypoxanthine all turn into xanthine -> EXCESS uric acid. HGPRT - Hyperuricemia, Gout, Pissed off, Retardation, dysTonia. Tx = allopurinol (2nd - febuxostat; both xanthine oxidase inhibitors)
Only AA’s coded by ONE codon?
AUG - methionine; UGG - tryptophan
DNA polymerases involved in prokaryotic DNA replication?
DNA pol I = degrades RNA primer (5’->3’ exonuclease) and makes DNA. DNA pol III = major 5’->3’ synthesis activity; 3’->5’ exonuclease proofreading