Younger Review Flashcards
What does PRPP synthetase make?
PRPP
Where does the ribose-5P come from?
HMP shunt, it then makes PRPP
What does PRPP amidotransferae make?
PRNH2
Takes PRPP and makes PRNH2 out of it
What is the regulated committed step in Purine synthesis?
PRPP amidotransferase
What are the two enzymes of purine synthesis
PRPP synthetase and PRPP amidotransferase
What are the two possible fates of PRPP?
Go into purine synthesis or it can have a pyrimidine base added onto it
What is the regulated committed step for pyrimidine synthesis
CPS II
What does CPS II do?
Starts making the pyrimidine base
What is a positive regulator for PRPP synthetase?
Inorganic phosphate
Methotrexate
- folic acid analog
- an anti tumor drug that inhibits dihydrofolate reductase
- no DHF to THF, no dTMP
- can’t make DNA
Trimethoprim
- same as methorexate but works on prokaryotes. Inhibits prokaryotic dihydrofolate reductase
- antibiotic, prok cant make DNA
Sulfonamides
- structural analog of PABA
- antibiotic
- competitive inhibit of bacterial production of folic acid
6-mercaptopurine
- purine analog
- inhibits PRPP amidotransferase
Hydroxyurea
- anti tumor drug that’s inhibits ribonucleotide reductase
- blocks ribonucleotide conversion into deoxyribonucleotide
- can treat sickle cell too
5-Fluorouracil
- antitumor drug
- inhibits thymidilate synthase
- no methylation of dUMP, so no dTMP
Folate
Derivatives are used as carbon donors, methyl groups
What is adenosine deaminase important for?
AMP catabolism
Adenosine deaminase deficiency
- Affects T and B cells
- SCID
Treatment for adenosine deaminase deficiency
- bubble
- bone marrow transplant
- landmark treatment with gene therapy
Xanthine oxidase
Converts purine excretion pathway intermediate (xanthine) to uric acid
Xanthine oxidase deficiency
- Overproduction of uric acid
- hyperuricemia
- gout
How do you treat xanthine oxidase deficiency?
Allopurinol
Slight deficiency of HGPRT
Purine deficiencies
Severe deficiency in HGPRT
Forces salvage purines to be excreted
100% excretion as uric acid accumulates dramatically causing Lesch-Nyah’s syndrome
How are nucleotides linked together in nucleic acids?
Phosphodiester bonds
How do nucleus acid strands associate with each other?
Antiparallel via base pairing using hydrogen bonds
What are the purines?
Adenosine
Guanine
What are the pyrimidines
Thymine
Uracil
Cytosine
How many bonds in GC paring?
3 hydrogen bonds
How many bonds in AT/AU bonds?
2 hydrogen bonds
DsDNA with a high GC content
Requires higher melting temp
DsDNA with high AT content requires
Lower melting temp
Chargaffs rule
A%=T%, C%=G%, A%+T%+G%+C%=100%
DNA gyrase
- prokaryote replication
- topo II
- cuts both strands to INTRODUCE supercoils and separate linked replicated DNA
What inhibits DNA gyrase?
Antibiotic quinolones
Semiconservative DNA replication
1 parent strand
1 new strand
Origin of replication in prokaryotes
1 origin of replication
Origin of replication in eukaryotes
Multiple sites
High AT content, easy to melt
Bi directional replication
Run in opposite directions with replication fork
Replication fork
Area where DNA helicase opens the two strands
single stranded binding proteins (SSBs)
Prevent reannealing
Topoisomerase I
- nick in 1 strand
- receive supercoiling
Topoisomerase II
- nick in 2 strands
- receive supercoiling
What direction is DNA polymerized?
5’-3’
Requires RNA primer
Leading strand
-produced continuously 5’-3’
Lagging strand
- discontinuous production
- okazaki fragments
Okazaki fragments
Short stretches of replicated DNA formed as the replication fork moves upstream of the origin of replication for that strand
5’-3’
Primase
Adds rNTPs to form a primer and 3’-OH site for DNA polymerase activity
Primase in eukaryotes
Is part of DNA polymerase
DNA ligase
Seals all the nicks, form phosphodiester bonds
Telomeres/telomerase
Telomerase is a reverse transcriptase that extends the ends of eukaryotic DNA using RNA as a template to function as a DNA polymerase
What is the disease associated with strand directed mismatch repair?
HNPCC (hereditary nonpoltposis colorectal cancer)
-terminally differentiated cell starts having telomerase activity
Cause and DNA defect associated with xeroderma pigmentosum
Thiamine diner causes by UV light
- cant fix damage
- Cant repair thiamine dimers
DNA replication overview
- initial strand separation (high AT content)
- SSB proteins prevent reannealing
- helicase unwinds DNA at the replication fork
- topoisomerase relieves supercoiling ahead of fork
- leading strand synthesized continuously
- lagging strand synthesized discontinuously
- primase lays down an RNA primer to being each new strand
- Pol III extends the leading and lagging strand
- Pol I removes RNA primers and replaces them with DNA
- DNA ligase seals the nick in the strands
Transcription: sigma factor
Recognizes promoter sequence in prokaryotic RNA polymerase
Transcription: core enzyme
Gets recruited and does transcription
What is sigma factor + core enzyme?
Holoenzyme
Rifampin
Binds and inhibits core enzyme
Prokaryotic promoter sequences
-35
TATA(pribnow)
Eukaryotic promoter sequence
CAT
TATA (hogness)
Shine dalgarno sequence
Start site for translation in prokaryotes. Polycistronic
Polycistronic mRNA
Specific to prokaryotes
What are the two ways that translation terminates in prokaryotes
-rho dependent
-Rho independent
GC stem loop, poly U tail
Systemic lupus erythmatosus
-dsDNA and snRNPs are identified by the adaptive immune system, young females, weakness and joint pain, butterfly rash
Alpha amantin
- toxin from the death cap mushroom causes 95% of mushroom fatalities
- toxin functions by binding RNA polymerase II and inhibits transcription/ mRNA synthesis in eukaryotes
Start codon
AUG
Stop codons
UGA, UAA, UAG
Ribosomes translating secretory proteins
Are targeted to the ER where they continue to translate the protein into the ER.
-hydrophobic peptide signal emerging from the ribosome plays a role in this
Aminoacyl-tRNA synthetase
- decoder
- recognize codon
- attach AA to tRNA
