Biochem Night School II.1

  1. cDNA
    • clonal DNA from mRNA reversetranscripted
    • lacks introns
  2. Cre-lox system
    • manipulates genes after a point in development
    • because for some genes if you mess with them too early you cause death
  3. dsRNA
    • injected into human cells promotes target mRNA degradation
    • gene “knock down”
  4. pleiotropy
    one gene contributes to multiple phenotypic effects
  5. somatic mosaicism
    mutation after fertilization propagates a certain mutation in only some tissues
  6. gonadal mosaicism
    mutation occurred that affects germ cells of an individual, but is not present in the individual
  7. McCune-Albright syndrome
    • lethal if occurs before fertilization, only viable if somatic mosaicism
    • G protein signaling issue leading to constituitive G protein function in some tissues causing autonomous hormone effects/production
    • unilateral cafe au lait, polyostotic fibrous dysplasia (fibrous bone that is weak, poly meaning multiple affected bones), precocious puberty, hyperthyroidism, Cushing syndrome, growth
  8. uniparental disomy (and flavors)
    • 2 copies from one parent, none from the other
    • AR disease when only one parent is carrier
    • heterodisomy if meiosis I
    • isodisomy if meiosis II
  9. Hardy-Weinberg p and q and X linked too
    • p and q are allelic frequencies
    • p2 is homozygosity p
    • 2pq is heterozygosity
    • q2 is homozygosity q
    • if X linked frequency of disease in males is q and females is q2
  10. Prader-Willi
    • maternal imprinted and paternal deleted/mutated, on chrom 15
    • hyperhpagia, obesity, intellectual disability, hypogonadism, hypotonia
    • also maternal uniparental disomy
  11. Angelman syndrome
    • paternal imprinted and maternal deleted/mutated, on chrom 15
    • inappropriate laughter, seizures, ataxia, severe intellectual disability
    • “happy puppet”
    • also paternal uniparental disomys
  12. X linked dominant inheritance
    • fathers to ALL daughters and no sons
    • mothers to both 50/50 shot
  13. mitochondrial inheritance
    • mothers to ALL children to some degree
    • fathers to no one
  14. Osler-Weber-Rendu
    • AD
    • telangiectasias, epistaxis, skin discolorations, AVMs (death in brain), GI bleeding, hematuria
  15. Li Fraumeni likely cancers
    • AD
    • SBLA cancer
    • sarcoma, breast, leukemia, adrenal
  16. Marfan
    • AD
    • cystic medial necrosis of aorta
    • lens sublux up and out
    • floppy mitral
  17. von Recklinghausen
    • NF1
    • AD
    • cafe au lait
    • cutaneous neurofibromas, optic glioma, pheochromocytomas, Lisch nodules (iris hamartoma)
  18. NF2
    • AD
    • bilateral acoustic schwannoma, juvenile cataracts, meningiomas, ependymomas
  19. cystic fibrosis (gene, what happens, dx)
    • AR
    • chromosome 7, deletion of Phe508 is most common
    • misfolded protein (#1), retained in RER Cl channel for lung/GI secretion and sweat reabsorption
    • decreased Cl secretion in lungs/GI reduces Na secretion. H20 pulled back into cell causing less water in airway so more mucous by percent (thicker mucous)
    • negative transepithelial potential difference
    • Cl>60mEq/L in sweat
    • contraction alkalosis and hypokalemia because losing Na through sweat so kidneys waste K and H
    • new born screening of immunoreactive trypsinogen
    • nasal polyps, nail clubbing
  20. Duchenne muscular dystrophy
    • XR with frameshift or nonsense truncating dystrophin links actin to transmembrane alpha and beta dystroglycan. lack causing myonecrosis
    • first pelvic girdle then spread, calf pseudohypertrophy b/c first not affected and get used more, then replaced by fat
    • use of upper extremities to stand (Gower maneuver)
    • waddling gait
    • dilated cardiomyopathy is fatal
    • elevated CK and alkolase
    • western blot confirms
  21. Becker mucsular dystrophy
    • XR with non-frameshift insertions/deletions leading to partially functional dystrophin gene
    • less sever with adolescence or early adulthood onset
  22. myotonic type 1
    • AD CTG trinucleotide repeat and expansion of DMPK (dystrophin myotonica protein kinase
    • muscle wasting, myotonia (delayed relaxation), cataracts, testicular atrophy, frontal balding, arrhythmia
    • mytonia, mytesticles, mytoupee, myticker
  23. fragile X
    • XD CGG trinucleotide repeat in FMR1, methylating and reducing expression
    • post pubertal macroorchidism, intellectual disability, long face, large jaw, large forward facing (everted) ears, autism, MV prolapse
  24. Down syndrome
    • 95% meiotic nondisjunction, 4% unbalanced Robertsonian 14;21, 1% somatic mosaicism
    • duodenal atresia, Hirschsprung, AV septal defect, Brushfield spots (white iris dots), early Alzheimers
    • first trimester decreased serum PAPP-A, increased free beta hCG. Also nuchal translucency increased
    • 2nd tri decreased alpha fetoprotein and estriol, increased beta hCG and inhibin A
  25. Edwards syndrome
    • chromosome 18 trisomy
    • rocker bottom feet, small jaw, low ears, clenched hands overlapping fingers,prominent occiput, congenital heart disease
    • first trimester decreased serum PAPP-A and beta hCG
    • 2nd tri decreased alpha fetoprotein, beta hCG, estriol, and decreased/normal inhibin A
  26. Patau syndrome
    • trisomy 13
    • rocker bottom feet, small eye(s), small head, cleft lip/palate, holoprosencephaly, polydactyly, congenital heart disease, cutis aplasia
    • first trimester decreased PAPP-A and beta hCG
  27. Robertsonian translocation
    • 2 acrocentric chromosome long arms (q) get together and leave the little p bits
    • balanced don’t cause any problems, but then you can give your kid an unbalanced and that causes chromosomal abnormalities
  28. Cri-du-chat
    • microdeletion of short arm of 5
    • microcephaly, intellectual disability, high pitched cry/mew, epicanthal folds, ventral septal defect
  29. williams syndrome
    • microdeletion of long arm 7 (includes elastin gene)
    • elfin face, intellectual disability, hypercalcemia (increased VIT D sensitivity), friendly with strangers, supravalvular aortic stenosis
  30. DiGeorge
    • microdeletion of 22q11 (chrom 22 long arm that is)
    • cleft palate, abnormal face, thymic aplasia, T cell lack, tet of fallot, truncus arteriosus, hypocalcemia (lack PTH)
    • velocardiofacial syndrome is same but just palate, facial, and cardiac
  31. VIT A
    • retinol
    • visual pigments, epithelial specialization (pancreatic, mucin secreting), prevents squamous metaplasia
    • nigh blindness, dry scaly skin, corneal degeneration, bitot spots on conj (chunky fat looking stuff), immunosuppression
    • isotretinoin is a teratogen, requires pregnancy test and 2 forms of contraception
  32. VIT B1
    • thiamine
    • thiamine pyrophosphate (TPP) is a cofactor for pyruvate dehydrogenase (glycolysis to TCA), alhpa ketoglutarate dehydrogenase (alphaKG to succinyl CoA in TCA), transketolase (HMP shunt)
    • impaired glucose breakdown worsened by glucose xfusion so low ATP and highly aerobic tissues first affected (brain and heart)
    • dilated high output heart failure, edema (wet beriberi)
    • polyneuritis, symmetrical muscle wasting (dry beriberi)
    • Wernicke-Korsakoff is confusion, ophthalmoplegia, ataxia
    • think ATP for alpha ketoglutarate, transketolase, and pyruvate dehydrogenase
  33. VIT B2
    • riboflavin
    • FAD and FMN (oxidizer flavins) for redox reactions, succinate dehydrogenase in TCA (succinate to fumarate)
    • cracked lips at the corners (cheilosis) and corneal vascularization
    • 2Cs
  34. VIT B3
    • niacin aka nicotinic acid
    • NAD and NADP oxidizers derived from tryptophan where synthesis needs B2 and B6. dyslipidemia treatment lowering VLDL and raising HDL
    • glossitis, pellagra if severe caused by malignant carcinoid syndrome (decreased tryptophans b/c they're used to synth serotonin and dopamine instead), Hartnup disease (decreased tryptophan absorption), INH (by decreasing B6)
    • pellagra is diarrhea, dementia, dermatitis (hyperpigmentation of sun exposed)
  35. Hartnup disease
    • AR reducing tryptophan absorption lowering melatonin, serotonin, and niacin levels
    • pellagra
    • treat with high protein diet and nicotinic acid (niacin)
  36. VIT B5
    • pantothenic acid
    • component of CoA, fatty acid synthase, acne, enteritis, alopecia, adrenal insuf
    • coA, acne, abdominal pain, alopecia, adrenal insuf
  37. VIT B6
    • pyridoxine
    • converted to pyridoxal phosphate used in transamination, decarboxylation, glycogen phosphorylase, synthesis of heme, cystathionine, niacin, histamine, serotonin, epinephrine, NE, dopamine, GABA
    • INH and OCPs: convulsions, hyperirritability, peripheral neuropathy, sideroblastic anemia
  38. VIT B7
    • biotin
    • cofactor for carboxylation that adds a carbon like pyruvate carboxylase (pyruvate to oxaloacetate), acetyl CoA carboxylase (acetyl CoA to malonyl CoA), propionyl CoA carboxylase (propionyl CoA [3C] to methylmalonyl CoA
    • dermatitis, alopecia, enteritis, rare but antibiotics and raw egg white ingestion
    • avidin in egg whites avidly binds biotin
  39. VIT B9
    • folate
    • converted to THF a coenzyme for methylation, synthesis of nitrogenous bases in DNA and RNA
    • megaloblastic anemia, glossitis
    • icnreased homocysteine, normal methylmalonic acid
    • alcoholism, pregnancy, phenytoin, sulfonamides, methotrexate
    • neural tube defects in children
  40. VIT B12
    • cobalamin
    • cofactor for methionine syntahse and methylmalonyl CoA mutase
    • megaloblastic anemia, paresthesias (subacute combined degeneration [dorsal columns, lateral corticospinal, spinocerebellar] prolonged is irreversible) by low myelin
    • elevated homocysteine and methylmalonic acid
    • gastic bypass, long malabsorption, absence of terminal ileum (Chron), veganism, pernicious anemia (anti intrinsic factor Ab for dx)
  41. VIT C
    • ascorbic acid
    • antioxidant, keeps iron reduced to Fe2+ for absorption, hydroxylation of proline and lysine, dopamine beta hydroxylase (dopamine to NE)
    • part of methemoglobinemia treatment
    • scurvy (gum bleed, petechiae, hemarthrosis, anemia, poor wound healing, corkscrew hair, weak immunity)
  42. VIT D
    • D2 from plants converted to D3 by sun, D3 from milk, 25-OH D3 is storage form, 1,25(OH)2 D3 is active
    • absorption of Ca and PO
    • bone pain and deformity rickets/osteomalacia, hypocalemic tetany
    • supplement infant if breast feeding
    • granulomatous diseases (sarcoid) activate epithelioid macrophages to cause excess leading to hypercalcemia, hypercalciuria, loss of appetite, stupor
  43. VIT E
    • tocopherol/tocotrienol
    • antixoidant protecting RBCs from ROS, can enhance warfarin anticoag
    • hemolytic anemia, acathocytosis, muscle weakness, posterior column and spinocerebellar tract demyleiantion
    • similar to B12 but without megaloblastic anemia or increased methylmalonic acid
  44. VIT K
    • phytomenadione, phylloquinone, phytonadione
    • cofactor of gamma carboxylation of glutamic acids on clotting factor proteins (2, 7, 9, 10, C, S), synthed by gut flora
    • seen in neonatal hemorrhage (lack gut flora), prolonged use of broad spectrum antibiotics
    • not in breast milk, given as injection
  45. zinc
    • zinc fingers (transcription), zinc for wound healing, a million enzymes
    • delayed wound healing, hypogonadism, less pubertal hair (facial, axillary, pubic), can’t taste (dysgeusia), anosmia, acrodermatitis enteropathica, may predispose to alcoholic cirrhosis
  46. kwashiorkor
    • protein malnutrition leading to edema (low oncotic pressure), fatty liver change, anemia
    • MEAL (malnutrition, edema, anemia, liver)
  47. marasmus
    total caloric malnutrition resulting in emaciation, maybe edema
  48. ethanol and metabolism
    • NADH formed with breakdown, increases NADH/NAD ratio making pyruvate go to lactic acid (lactic acidosis)
    • oxaloacetate to malate (preventing gluconeogenesis, causing fasting hypoglycemia)
    • dihydroxyacetone phosphate to glycerol-3-phosphate (combines with FA to make triglyceride, causing hepatosteatosis)
    • decreasing TCA cycle so acetyl CoA is used for ketogenesis (ketoacidosis) and lipogenesis instead (hepatosteatosis)
  49. mitochondria (what takes place inside)
    fatty acid oxidation (beta ox), ketogenesis
  50. MELAS
    • mito disease
    • failure of oxidative phospohrylation, leading to mitochondrial encephalopathy, lactic acidosis, stroke-like episodes (migraine, strokes, cortical blindness)
    • ragged red fibers on muscle biopsy, Gomori trichome shows mitochondrial proliferation
  51. MERRF
    • mito disease
    • myoclonic epilepsy with ragged-red fibers, you get epilepsy triggered by things and muscle weakness
    • Gomori trichrome for mitochondria
  52. LHON
    • mito disease, NADH dehydrogenase
    • leber hereditary optic neruopathy
    • young adult onset blindness in one eye then the next weeks-months apart, retinal ganglion degeneration
    • edematous nerve with telangiectasisas
  53. cytoplasm (what takes place in there)
    fatty acid synth, cholesterol synth, nucleotide synth
  54. Gardner's syndrome
    • phenotypic variant of FAP with fibromas aka desmoid tumors (usually peritoneal from colon surgery) and osteomas (usually facial)
    • also thyroid
  55. Turcot
    • FAP with glial cancers and meduloblastomas
    • the genes are actually biallelic mismatch repair genes
Card Set
Biochem Night School II.1
Because the first night school wasn't good enough!