GoConqr has a new look! Let us know what you think.

Sign up free

Flashcards

Biochemistry - Step 1, first aid

Katharina Raschdorf English 57 cards

Biochemistry - Step 1, first aid

Cards in this deck (57)

  1. 1Chromatinnegative DNA loops twice around positive Histone octamer (H2a &B, H3, H4)
    histones rich in lysine and arginine
  2. 2Heterochromatin vs. Euchromatincondensed, inactive, inaccessible, highly methylated, low acetylation
    eg. Barr body, inactive DNA etc.
    vs.
    accessible and active
  3. 3DNA vs. Histone methylationDNA methylation at CpG islands makes them mute and represses transcription
    vs.
    at histones makes them USUALLY mute
  4. 4Histone acetylationmakes DNA active by relaxing DNA coiling
  5. 5nucleoTides vs nucleoSidesbase + sugar + phosphaTe (3-5` phosphodiesterase bond)
    vs.
    base + Sugar
  6. 6Purines vs. pyramidinesPURe As Gold (adenosine & guanine)
    - need GAG amino acids and THF
    - from de novo or recyling
    vs.
    CUT the PY (pie)
    - need aspartate
  7. 7disrupt synthesis of pyrimidine vs. purine vs. bothLEFLUNOMIDE (dihydroorotate dehydrogenase)
    MTX, TMP, PYRIMTHAMINE (dihydrofolate reductase)
    5-FU (forms 5-F-dUMP & dec. dTMP)
    vs.
    6-MERCAPTOPURINE
    MYCOPHENOLATE and RIBAVIRIN (ribonucleotide dehydrogenase)
    vs.
    HYDROXUREA (ribonucleotide reducatse)
  8. 8purine salvage deficiencies ADENOSINE DEAMINASE DEFICIENCY- autosomal recessive SCID
    - dec. adenosine ->inosine degrad (dATP buildup)
    - lymphocyte toxicity
  9. 9purine salvage deficiencies LESCH- NYHAN SYNDROME-absent HGPRT
    - no conversion -1. hypoxanthine to IMP
    2. guanine to GMP
    - X-linked rec. (inc. uric acid & de novo pur.)
    - HGPRT (Hyperuricaemia, Gout, Pissed off (aggression and self-mutiliation), Retardation & dysTonia
  10. 10DNA replication I- semiconservative
    -continouse & Okazaki fragments
    - 5->3`direction
    - start at Origins of replication (TATA box)
  11. 11DNA replication II-helicase (unwinding)
    -topoisomerases (remove supercoils, IRINOTECAN& ETOPOSIDE inhibit eukaryotic topoisomerase I & II respec.; FLUOROQUINOLONES block prokaryotic TI II (DNA gyrase) & TI IV
    - primaes (makes RNA primer)
    - DNA Pol III & I (prokaryotes, many drugs have modified 3`OH -> prevent nucleotide addition by pol III -> chain termination), pol I replaces primer
    - DNA ligase (joins okazaki)
    - Telomerase (RNA-dep-DNA polymerase, adds DNA to 3`of chromosomes, often deregulated in cancers)
  12. 12DNA mutationssilent- same AA , often in wobble base
    missense.- substitutions, other AA, Sickle cell, conservative if AA similar properties
    nonsense- early stop codon
    frameshift - small deletion/insertion, altered ORF, tay-sachs or DMD
    splice site - retained intron, forms of epilepsy, cancer, beta-thalas
  13. 13nucleotide excision repair defectsXERODERMA PIGMENTOSUM
    - no repair of pyrimidine dimers from UV
    -autosomal recessive
    - usually repair of bulky, helix-distorting lesions in G1 by specific endonulcleases, DNA pol & ligase
  14. 14mismatch repair defectsmismatched nucleotides recognised in new DNA strand, removed &gap filled in G2
    but if defect:
    LYNCH SYNDROME
    -hereditary nonpolyposis colorectal cancer
  15. 15base excision repairimpo in spontaneous/toxic deaminations
    - throughout cell cycle
    - GEL PLease
    1. glycosylase 2. AP-Endonuclease, 3. Lyase, 4.DNA pol beta 5.ligase
  16. 16RNA polymerase inhibitorsACTINOMYCIN D - inhibits RNA pol in both euk. & prokaryotes
    RIFAMPIN- inhibits prok. DNA-dep-RNA-pol
  17. 17RNA polym. in eukarytestype I - rRNA
    type II- mRNA
    type III - 5sRNA & tRNA
    (labelled I-III as their products in protein synthesis in order)
  18. 18RNA processinginitial hnRNA modified to mRNA by 5`capping, polyA-tail at 3`& splicing (snRNPs, spliceosome, loop) - all in nucleus
    cytoplasm - translation & control at P bodies (exonucleases, microRNAs, decapping enzymes etc.), translation can be repressed by miRNA (target 3`untranslated region of mRNA)
  19. 19anti-Smith antibodies & anti-U1 RNP antibodiesIg to spliceosomal snRNPs
    - highly specific for SLE
    &
    Ig to snRNP70
    - mixed connective tissue disorder (MCTD)
  20. 20Fabry diseaseX-linked recessive alpha-galactosidase A deficiency
    - accumulation of sphingolipid globotriaosylceramide
    nueropathic pain, RF, cerebrovascular disease, telengiectasia, angiokeratomas & CV disease
  21. 21tRNAanticodon loop
    CCA (carry AAs) at 3`- acceptor stem
    T arm - Tethers tRNA to ribosome
    D arm - Detects aminoacyl tRNA synthetase -> enzyme that charges tRNA with correct AA
  22. 22TranslationINITIATION
    -Initiation Factors in eukar. assemble 40+60S=80S; in prokary 30+50S=70S
    ELONGATION
    - mRNA read in 5`->3`
    - "going APE" A- site (incoming AA-tRNA), P site (accommodates growing peptide), E site (exit site of empty tRNA)
    TERMINATION
    - stop codon recognised by Release Factor and complete polypeptide released
  23. 23Cell cycleMitosis - pro-, meta-, ana- & telophase; cytokinesis; interphase -> G1 (growth)/ Go; S (synthesis) & G2
    CDKs activated by cyclins -> phosphorylation complex allowing cycle progression
    Tumour suppressor- p53 induces p21 that inhibits CDKs (no G1 ->S) & activates Rb
    - mutations in p53 -
    LI-FRAUMENI SYNDROME
  24. 24free ribosomes vs. rER vs. sERsynthesis of cytosolic/organellar proteins
    vs.
    synthesis of secretory proteins & N oligosaccharide addition; Nissle bodies (neuronal rER ) also peptide NT synthesis
    vs.
    steroid synthesis and detoxification (gonads, adrenals, liver cells)
  25. 25Peroxisomal diseasesneurologic-deficient myelin plasmalogens
    ZELLWEGER SYNDROME
    hypotonia, seizures, hepatomegaly, death
    REFSUM DISEASE
    - scaly skin, ataxia, cataracts/night blindness, short 4th toe, epiphyseal dysplasia
  26. 26I cell disease- inherited lysosomal storage disorder
    - N-acetylglucosaminyl-1-phosphotransferase defect
    - decreased mannose-6-phosphate on glycoproteins in golgi so proteins are secreted & not stored in lysosomes
    -coarse facial features, clouded corneas, restricted joint movement, childhood death, high plasma levels of lysosomal enzymes
  27. 27markers tumours intermediate filamentsvimentin- mesenchymal
    desmin- muscle
    cytokeratin- epithelial
    GFAP- astrocytoma, glioblastoma
    neurofilaments - neuronal
  28. 28KARTAGENER SYNDROME1° ciliary dysfunction
    - infertility, ectopic pregancy, bronchiectasis, ear & sinus infections, situs inversus
    - NORMAL CILIA- 9 doublet + 2 singlet microtubule arrangement (doublets linked by dynein - ATPase that is defective here) + basal body of 9 microtubule triplets
  29. 29CARDIAC GLYCOSIDES -DIGOXIN & DIGITOXINinhibit sodium- potassium pump ->
    indirect inhibition of N+/calcium exchange ->
    increased Introcellular calcium ->
    increased contractility
  30. 30CollagenBe So Totally Cool, Read Books
    Type I - bone, skin, tendon
    Type II - Cartilage, nucleus pulposus
    Type III - Reticulin (BVs, skin, fetal tissue, granulation tissue and uterus)
    Type IV - BM, Basal lamina, lens
  31. 31collagenopathiesOSTOGENESIS IMPERFECTA - most commonly dec in normal col. I, COL1A1/2, fractures, blue sclerae, dental problems, hearing loss
    EHLERS DANLOS SYNDROME
    - problems cleaving pro- to tropocollagen or crosslinking of tropocollagen
    - vascular type -> lack of Type III
    bleeding, aneurysm, organ rupture
    -classical type -> COL5A1/2, col 5 defect; hyperextensible skin/joints
    ALPORT SYNDROME
    - genetic Type IV, hearing loss, RF & lens
    GOODPASTURE SYNDROME
    - type IV targeted by autoantibodies
    MENKES DISEASE
    - X linked rec defect in copper absorption -> dec lysyl oxidase -> dec cross-linking
    - brittle hair, growth retardation, hypotonia    collagenopathies
  32. 32collagen synthesis and structure1. preprocollagen, alpha chains, 1/3 glycine
    2. hydroxylation of pro & lys; Vit C needed (SCURVY!)
    3. glycosylation of pro-a-chains, procollagen via H-& disulfide bonds -> triple helix
    4.-5. exocytosis & proteolytic cleavage of termini (to insoluble tropocollagen)
    6. cross linking by covalent lysine, hydroxylysine linkages
  33. 33alpha-1-antitrypsin deficiencyusually inhibits elastase so deficiency results in excess elastase activity & EMPHYSEMA and/or liver disease
  34. 34Marfan syndromeautosomal dominant defect in FIBRILLIN -
    FBN1 gene (glycoprotein forming sheath around elastin)
    - tall, lanky, aortic aneurysm, pectus excavatum/carinatum, hypermobile joints, subluxation of lenses, floppy mitral valves
  35. 35Southern Northern western southwestern blottingDNA
    RNA
    Protein
    DNA-binding proteins
  36. 36Phenylketonuriaincrease phenylalanine due to low phenylalanine hydroxylase (tyrosine becomes essential AA due to low conversion from PAla)
    inborn error of metabolism
    light skin, ID, seizures, must body odor, low birth weight
    - ex of gene pleiotropy - one gene multiple phenotypic effects
  37. 37loss of heterogenositytumour suppressor gene mutations
    - if one is mutated other allele must also be deleted/mutated
    - Two hit hypothesis - eg. Li Fraumeni
    - NOT true for oncogenes
  38. 38McCune-Albright syndromesomaticmosaicism
    -affects G protein signaling
    -unilateral cafe- au-lait spots, polyostotic fibrous dysplasia & endocrinopathy    McCune-Albright syndrome
  39. 39Uniparental disomyBoth chromosomes from single parent
    - Angelman (5% cases) & PW (25%)
    - patient with recessive disease but only one parent is carrier
    - HETERODISOMY-> heterozygous -> meiosis I error
    - ISODISOMY-> homozygous -> meiosis II or chromosomal duplication
  40. 40Imprintingat some loci only one allele is active & the other one inactive -> because that allele inactivated by methylation, deletion of the active allele results in disease
  41. 41Prader- Willi syndromematernal imprinting -> maternal gene normally silent while PATERNAL inactivated; or maternal uniparental disomy (25%) chromosome 15
    - hyperphagia, obesity, ID, hypogonadism & hypotonia
  42. 42Angelman syndromepaternal imprinting -> paternal inactive and MATERNAL deleted or
    paternal unilateral disomy (5%)
    chromosome 15
    inappropriate laughter, ID, seizures, ataxia
  43. 43Hypoposhatemic ricketsx-linked dominant (mum-to 50% of sons &daughters; dad- to all daughters, no sons)
    - inc Phosphate wasting at proximal tubule
    - Ricktes-like presentation
  44. 44MELAS syndromemitochondrial disorder leading to failure of oxidative phosphorylation ->
    MELAS -> Mitochondrial encepalopathy, Lactic Acidosis, Stroke-like episodes
    muscle biopsy -> "ragged red fibres" - accumulation on diseased mitochondria
  45. 45Types of inheritanceAutso. dom. ->m&fem., often structural, 50% affec., pleiotropic &variable expression
    Autos. rec. -> often enzymatic def., inc in consanguinity, ,25,50,25%
    X rec-> skips generat., no male-to-male
    X dom -> dads transmit to all daughters but to no sons
  46. 46Duchenne muscular dystrophyX-linked, frameshift/nonsens -> truncated/absent dystrophin;
    progressive myonecrosis &pseudohypertrophied calfs, waddling gait, <5y, dilated cardiomyopathy, + gower sign
    - inc CK & aldolase-
    (dystrohin anchors actin to transmem. alpha & beta dytroglycan &thus to ECM)    Duchenne muscular dystrophy
  47. 47Becker muscular dystrophyX-linked, non-frameshift deletions, partially functional dystrophin -> less severe & adolescent onset
    NOTE: deletions can cause both DMD & BMD depending on type & extend of deletion
  48. 48Myotonic type I MDauto. dom., CTG repeat in DMPK (myotonin protein kinase)
    - cataracts, toupee, gonadal atrophy, hypotonia & muscle wasting, arrhythmia    Myotonic type I MD
  49. 49Cystic fibrosisauto rec.,CFTR (chro7), common delPhe508,
    misfolding ->no transport to cell membrane-> dec Cl- secretion & high IC Cl+ -> compensatory Na+ absorption -> H20 follows -> thick mucous lungs/GI
    infections, alkalosis, hypokalaemia, inc immunoreactive trypsinogen, bronchitis &bronchiectasis (reticulonodular CXR), pancreatic insufficiency, steatorrhea, infertility in men, nail clubbing, meconium ileus in newborn    Cystic fibrosis
  50. 50FRAGILE XCGG repeat in FMR1 gene-> hypermethylation -> dec expression ;
    - most common form of inherited ID/autism
    macroorchidism, large jaw, everted ears & mitral valve prolapse, long face    FRAGILE X
  51. 51Down syndrome trisomy 21- ID, single palmar crease, epicanthal folds prom., AV septal defect, duodenal atresia, brushfield spots, inc risk of ALL & AML, Hirschsprung, early onset Alzheimer
    - 95% -> meiotic nondysunction; 4% -> unbalanced robertsonian translocation (chro. 14 &21); 1% -> mosaicism
    -1st trim.-> inc nuchal transluc., hypoplas. nasal b.., inc β-hCG, dec PAPP-A
    - 2nd ->dec α-fetoprotein, estriol & inc inhibin A & β-hCG    Down syndrome trisomy 21
  52. 52Edwards syndrome trisomy 18- PRINCE Edward -> prominent occiput, Rocker-bottom feet, ID, nondysjunction, clenched fist, low-set ears + small jaws (micrognathia), heart defects
    - death usually by age 1
    - 1st trim. -> decrease in all -> PAPP-A & β-hCG, α-fetoprotein, estriol & inhibin A (may be normal)    Edwards syndrome trisomy 18
  53. 53Patau syndrome trisomy 13-ID, rocker-bottom feet, cleft palate, microcephaly, microphtalmia, holoprosencephaly, polydactyly, cutis aplasia, heart defects
    - like edwards same death prognosis & PAPP-A & β-hCG decrease in 1st trim.    Patau syndrome trisomy 13
  54. 54non-dysjunctionnon-dysjunction
  55. 55Cri du chat syndromemicrodel of p arm of chromosome 5
    - microcephaly, high-pitch, meowing, ID, epicanthal folds & VSD    Cri du chat syndrome
  56. 56Williams syndromemicrodeletion 7q-
    -ID, distinct "elfin" facies (elastin gene deleted), hypercalcemia, extreme friendliness, CV defects    Williams syndrome
  57. 57CATCH -22 syndromes - DiGeorge & Velocardioacial-microdeletion at 22q11; aberrant development of 3rd&4th branchial plexus
    - Cleft palate, Abnormal facies, Thyic aplasia, Cardiac defects, Hypocalcaemia
    1. DI GEORGE SYNDROME - thymic& parathymic aplasia & cardiac defetcs
    2. VELOCARDIOFACIAL SYNDROME - palate, facial, cardiac

Information

Description
Flashcards on Biochemistry - Step 1, first aid, created by Katharina Raschdorf on 15/01/2018.
Created by
Katharina Raschdorf · Jan 2018
Updated
Feb 3, 2018
Views
0
Rating

Feedback

What is it about?

What do you think of the new look?

How do you like it?