USMLE Step 1: Biochemistry & other

most common cause of primary spontaneous pneumothorax

increased incidence of pulm. hypertension

most common inherited bleeding disorder

Desmopressin: releases vWF & factor VIII from the endothelium

CNS tumors

Glia tumors

increased risk for endometrial adeno-ca

papillary necrosis & chronic interstitial nephritis

paraneoplastic snyndrome associated with neuroblastoma (increased nr. of copies of the N-myc)

• viral myocarditis (Coxsackie B)
• Peripartum cardiomyopathy
• Alcohol abuse
• chronic supraventricular tachycardias
• cardiotoxic drugs (e.g. doxorubicin)
• thiamine deficiency (wet beriberi)

C-myc = transcription activator

Multiple myeloma

Ergonovine can provoke coronary spasms

Clinical features

• most likely medulloblastoma or pilocytic astrocytoma
• brain imaging:
  • medulloblastoma: only solid
  • pilocytic astrocytoma: cystic & solid components

1. condensed, inactive, inaccessible
2. less condensed, active, accessible

1. C-G base pairs on the template strand are methylated –> allows mismatch repair enzymes to distinguish between old & new strands
2. inactivates transcription of DNA
3. relaxes DNA coiling –>  transcription

1. 2 rings
   1. Adenosine
   2. Guanine: has a ketone
   3. Amino acides necessary for purine synthesis: glycine, aspartate, glutamine
2. 1 rings
   1. Thymine: has a methyl; in DNA
   2. Cytosine: becomes uracil when deaminated
   3. Uracil: in RNA
3. Bonds
   1. G-C bond stronger (3H)
   2. A-T bond (2H)

1. Base + ribose
2. Base + ribose + phosphate

• Purines:
  • start with sugar + phosphate (PRPP)
  • add base
• Pyrimidines:
  • make temporary base (orotic acid)
  • add sugar + phosphate (PRPP)
  • modify base

• Hydroxyurea: inhibits ribonucleotide reductase
• 6-mercaptopurine: blocks de novo purine synthesis
• 5-fluorouracil: inhibits thymidylate synthase (dTMP decreased)
• Methotrexate: inhibits dihydrofolate reductase (dTMP decreased)
• Trimethoprim: inhibits bacterial dihydrofolate reductase (dTMP decreased)

1. Inability to convert orotic acid to UMP
   1. due to defect in either orotic acid phosphoribosyltransferase or orotidine 5'-phosphate decarboxylase
   2. autosomal recessive
2. Findings
   1. increased orotic acid in urine
   2. megaloblastic anemia
   3. failure to thrive
   4. No hyperammonemia
3. Treament: oral uridine administration

• Adenosine deaminase deficiency
  • excess ATP and dATP imbalances nucleotide pool via feedback inhibition of ribonucleotide reductase –> prevents DNA synthesis and thus decreases lymphocyte count –> SCID (severe comined immunodeficiency disease)
• Lesch-Nyhan syndrome
  • absence of HGPRT –> excess of uric acid production & de novo purine synthesis
  • findings: retardation, self-mutilation aggression, hyperuricemia, gout, choreoathetosis
  • x-linked recessive

• Silent: same aa, often base change in 3rd position of codon
• Missense: changed aa (conservative - new aa is similar in chemical structure)
• Nonsense: change resulting in early stop codon (UAA, UGA, UAG)
• Frame shift: change resulting in misreading of all nucleotides downstream, usually resulting in a truncated, nonfunctional protein

1. Unwinds DNA template at replication fork
2. Create a nick in the helix to relieve supercoils created during replication
3. Makes an RNA primer on which DNA ppolymerase III can initiate replication
4. Prokaryotic only. Degrades RNA primer and fills in the gap with DNA
5. Prokaryotic only. Has 5' –> 30 synthesis and proofreads with 3' –> 5' exonuclease
6. Seals
7. Enzyme adds DNA to 3' ends of chromosomes to avoid loss of genetic material with every duplication

• Nucleotide exicision repair: mutated in xeroderma pigmentosum
  • specific endonucleases release the oligonucleotide-containing damaged bases
  • DNA polymerase and ligase fill and reseal the gap, respectively
• Base excision repair:
  • specific glycosylases recognize and remove damaged bases
  • AP endonuclease cuts DNA at apyrimidinic site
  • empty sugar is removed
  • gap is filled and resealed
• Mismatch repair: mutated in HNPCC
  • Unmethylated, newly synthesized string is recognized
  • mismatched nucleotides are removed
  • gap is filled and resealed

• Nonhomologous end joining: mutated in ataxia telangiectasia
  • brings together 2 ends of DNA fragments
  • no requirements for homology

1. AUG
   • Eukaryotes: codes for methionine
   • Prokaryotes: codes for formyl-methionine
2. UGA, UAG, UAA

1. Eukaryotes
   • RNA polymerase I makes rRNA
   • RNA polymerase II makes mRNA (opens DNA at promoter site); alpha-amanitin (death cap mushrooms) inhibits RNA polymerase II –> liver failure
   • RNA polymerase III makes tRNA
   • No proofreading function, but can initiate chains
2. Prokaryotes
   • 1 RNA polymerase (multisubunit complex) makes all 3 kinds of RNA