Biochemistry Flashcards
What is the rate limiting step in Pyrimidine synthesis?
Carbomoyl Phosphate 2
- cytosolic
What is the rate limiting step in purine synthesis?
Phosphoribosyl Pyrophosphate synthetase (PRPP synthetase)
What are the sources of carbons in the formation of purines?
CO2 Glycine Glutamine - provide Nitrogen Aspartate - provide nitrogen THF
What are the sources of carbon for Pyrimidine Synthesis?
- Aspartate
- CO2
- Glutamine = provides nitrogen (carbamoyl phosphate)
What inhibits ribonucleotide reductase?
Hydroxyurea
What inhibits dihydrofolate reductase?
Trimethoprim = bacteria Methotrexate = humans
What inhibits thymidylate synthase?
- 5-flourouracil
Inhibits IMP dehydrogenase?
Mycophenolate
Inhibits PRPP amidotransferase
- 6-mercaptopurine
Features of Orotic Aciduria
- Orotic acid in urine
- no elevation in ammonia
- failure to thrive
- megaloblastic anemia uncorrected by B12 or folate
- autosomal recessive
- due to deficiency in orodylate synthetase and OMP decarboxylase
Treatment = supplement dietary uridine
What accounts for positive charge in histones? Negative charge in DNA?
- Positive charge in histones = lysine and arginine
- Negative charge in DNA = phosphate
Topoisomerase Inhibitors
Fluoroquniolones = inhibit prokaryotic topoisomerase 2 (DNA grade and topo 4)
Etoposides = inhibit eukaryotic topoisomerase
AntiScl70 = antibody to topoisomerase in diffuse scleroderma
DNA polymerase differences in Prokaryotes vs. Eukaryotes
Prokaryotes
- DNA Poly 3 = builds both leading and and lagging strand
- DNA poly 1 = degrades RNA primer and replaces it with DNA
- have primase because it can’t make its own primer
- primosome = DNA helicase and primase (makes RNA primer)
Eukaryotes
- DNA polymerase alpha - makes own primer, and builds Okazaki fragments on lagging strand
- DNA polymerase delta = builds the leading strand
- DNA polymerase beta = DNA repair
- DNA polymerase gamma = replicates mitochondrial DNA
- telomerase is only found in eukaryotes and adds DNA to3’ ends to avoid loss of genetic material
Missense mutation
- occurs with sickle cell anemia = glutamic acid to valine
DNA repair
Single strand
- mismatch repair ==> HNPCC = increases risk of colon cancer
- nucleotide excision repair - for bulky damage ==> Xeroderma pigmentosum, Bloom syndrome (mutation of helicase)
- base excision repair - non bulky damage, removes altered base ==>
Double Strand
- Non-homologous end joining ==> ataxia telangiectasia, Fanconi anemia
- dsDNA repair = BRCA1 and BRCA2 mutations
DNA and RNA differences
- OH’ at 2’ position of ribose for RNA not in DNA
- total purines = total pyrimidines
- DNA and histone synthesis occurs during S phase
What is the difference between a 10nm and 30nm Chromatin
- there is no presence of H1 linker DNA in the 10nm
DNA –> 10nm chromatin –> 30nm chromatin –> 30nm with scaffolding proteins ==> Euchromatin —> high order packaging (HETEROCHROMATIN)
DNA methylation
Template strand cytosine and adenine are methylated in DNA replication. Help to distinguish between old and new strands in prokaryotes. DNA methylation at CpG islands repress transcription.
Histone Methylation vs. Acetylation
Methylation = represses DNA transcription Acetylation= relaxes DNA coiling and allows for transcription
Nucleotides
- deamination of cytosine makes uracil
- the more G-C bonds you have the higher the melting temp of DNA
- phosphates are linked from 3’ to 5’ on the ribose sugars
PNP deficiency
Severe deficit of T-cells
Adenosine Deaminase Deficiency
- will have excess ATP and dATP which causes feedback inhibition of ribonucleotide reductase
- autosomal recessive
- will cause SCID = defiance of both T and B cells = causes severe recurrent infections, chronic diarrhea, failure to thrive, no thymic shadow on CXR of newborn
Lesch Nyhan Syndrome
- defect in purine salvage pathway
- due to absent HGPRT
- causes excess uric acid production and de novo purine synthesis
- intellectual disability, self mutilation, gout, hyperuricemia, aggression, dystonia
Treatment = allopurinol and febuxostat
Genetic Code features
- unambiguous = each codon specifies only 1 amino acid
Degenerate/redundant = most amino acids are coded by multiple codons (except methionine and tryptophan = AUG and UGG)
Commaless, no overlapping = read from a fixed starting point as continuous except in viruses
Universal = genetic code is conserved throughout human population except in humans mitochondria