USLME Biochem - First Aid Exam With Questions And Answers

USLME Biochem - First Aid Exam With Questions And Answers Chromatin structure - Answer DNA exists in condensed chromatin f orm in order to fit in nucleus Negatively charged DNA loops twice around positively charged histone o ctamer (2 sets of H2A, H2B, H3 and H4) to form nucleosome "bead" Octomer subunits consist primarily of lysine and arginine amino ac ids (positively charged). H1 ties nucleosome beads together in a string Heterochromatin - Answer Condensed, transciptionally inactive , sterically inaccessible HeteroChromatin = Highly Condensed Euchromatin - Answer Less condensed, transciptionally active, st erically accessible Eu = true, "truly transcribed" Nucleotides - purines vs pyrimidines - Answer Purines (2 rings): A & G - PURe As Go ld: Purines - Adenine - Guanine Pyrimidines (1 ring): CTU - CUT the PY: Pyrimidines - Cytosine - Uracil (no methyl, RNA only) - Thymine (DNA only - has a methyl) Nucleotides: base pairs and bond strength - Answer G-C bonds (3 - bonds) stronger than A-T bonds (2 H-bonds). Increasing G-C content causes an increased melting temperatur e *Deamination of cytosine makes uracil Amino acids necessary for purine synthesis - Answer GAG Glycine Aspartate Glutamine Nucleotides - terminology - Answer Nucleoside = base + ribose Nucleotide = base + ribose + phosphate; linked by 3'-5' phosphodiest er bond De novo pyrimidine and purine synthesis - Answer Purines are made fro m IMP precursor Pyrimidines are made from orotate precursor with PRPP added later Ribonucleotides are synthesized first and are converted to deoxyxri bonucleotides by *ribonucleotide reductase* *Carbamoyl phosphate* is involved in 2 metabolic pathways: de novo pyrimidi ne synthesis and the urea cycle. - Ornithine transcarbamoylase deficiency (urea cycle) leasd to an accumulation of carbamoyl phosphate, which is converted to orotic acid Anti-neoplastic drugs that interfere with nucleotide synthesis - Answer 65-THM 6-mercaptopurine - blocks de novo purine synthesis 5-fluorouracil - inhibits thymidylate synthase (decreased dTMP) Trimethoprim - inhibits bacterial dihydrofolate reductase (decre ased dTMP) Hydroxyurea - inhibits ribonucleotide reductase (inhibits conversion to deoxy form) Methotrexate - inhibits dihydrofolate reductase (decrease d dTMP) Purine slavage deficiencies - Answer Adenosine deaminase deficie ncy - SCID (severe combined immunodeficiency disease) - bubble boy Excess ATP and dATP imbalances nucleotide pool via feedback inh ibition of ribonucleotide reductase - prevents DNA synthesis and decreased l ymphocyte count - a major cause of SCID Lesch-Nyhan syndrome - X-linked recessive - He' Got Purine Reco very Trouble - absence of HGPRT: converts hypoxanthine to IMP and guanine to GMP -->excess uric acid production - Findings: retardation, self-mutilation, aggression, hyperuricem ia, gout, chreoathetosis Purine and Pyrimidine transition vs transversion - Answer Transition - substituting purine for purine, or pyrimidine for pyrimidine Transversion - substituting purine for pyrimidine or vice versa Genetic code features - Answer Unambiguous - each codon specifies o nly 1 amino acid Degenerate/redundant - More than 1 codone may code for the sa me amino acid (Methionine encoded by only 1 codon - AUG) Commaless, nonoverlapping - Read from a fixed starting point as a continuous sequence of bases (some viruses are excepted) Universal - Genetic code is conserved throughout evolution (Exceptions: mitochondria, archaebacteria, mycobplasma and som e yeasts) Mutations in DNA - Answer Silent - same AA often base change in 3rd p osition of codon (tRNA wobble) Missense: changed aa (conservative - new aa is similar in chemical st ructure) Nonsense: Change resulting in early STOP codon Frame shift - change resulting in misreading of all nucleotides d ownstream, usually resulting in a truncated, nonfunctional protein Severity of damage: nonsense > missense > silent DNA replication - Answer Eukaryotic DNA replication is more complex than pr okaryotic processes, but uses many anzymes analogous to those listed below. In both cases, DNA replication is semiconservative and involves both continuous an d discontinuous (Okazaki fragment) synthesis. For uekaryotes, replication begi ns at a consensus sequence of base pairs. Origin of DNA replication - Answer Particular sequence in genome where DNA replication begins. May be single (prokaryotes) or multiple (e ukaryotes) Replication fork - Answer Y-shaped region along DNA template wher e leading and lagging strands are synthesized DNA Rep: Helicase - Answer Unwinds DNA template at replication fork DNA Rep: Single-stranged binding proteins - Answer Prevents strand s from reannealing DNA Rep: DNA topoisomerases - Answer Create a nick in the helix to relieve s upercoils created during replication - Fluroquinolones - inhibit DNA gyrase (specific prokaryoti c topoisomerase) - Adriamycin, etopiside both topoisomerase inhibitors DNA Rep: Primase - Answer Makes an RNA primer on which DNA polymerase III ca n initiate replication DNA rep: DNA Polymerase III - Answer Prokaryotic only. Elongates leading st rand by adding deoxynucleotides to the 3' end. Elongates laggin strand until it reaches primer of preceeding fragment. 3'->5' exonuclease activity "proofreads" ea ch added nucleotide - has 5' -->3' synthesis and proofreads 3' -->5' DNA Rep: DNA polymerase I - Answer Prokaryotic only. Degrades RNA primer and fills in the gap with DNA (excises RNA primer with 5' -->3' exonuclease) DNA Rep: DNA Ligase - Answer Seals okazaki fragment's together on lagging strand (lags away from fork, while leading strand leads into fork) DNA repair - Single strand - Answer Nucleotide excision repair - spe cific endonucleases release the oligonucleotide-containing damaged bases: DNA polym erase and ligase fill and reseal the gap respectively (mutated in xeroderma pigmentosu m which prevents repair of thymidine dimmers - "children of the night" - dry skin, mel anoma) Base excision repair - Specific glycosylases recognize and remove da maged bases, AP endonuclease cuts DNA at apyrimidinic site, empty sugar is reoved, and g ap filled and resealed Mismatch repair - Unmethylated, newly synthesized string is recognized, mismatc hed nucleotides are removed and the gap is filled and resealed - mut ated in HNPCC (Lynch syndrome)