Genetics Block 3

  1. What are the normal plasma levels of phenylalanine?
    What are the levels in phenylketonuria?
    • <1mM
    • >2mM
  2. Tetrahydrobiopterin is used by what enzymes?
    • Tyrosine Hydroxylase
    • Tryptophan Hydroxylase
    • Phenylalanine Hydroxylase
  3. Denovo synthesis of BH4 occurs from what molecule?
  4. Classic PKU is caused by what mutation?
  5. Smoking oxidizes what a.a in the active site of alpha 1 antitrypsin?
  6. Why would a pt with PKU present with albinism?
    • BH4 is needed for tyrosine hydroxylase
    • Tyrosine is a precursor to melanin
  7. What risk could high levels of phenylalanine pose to a fetus?
    it could act as a teratogen
  8. Alkaptonuria is caused by what deficiency?
    Homogenistic acid oxidase deficiency
  9. What happens in Alkaptonuria?
    • Dark connective tissue
    • Blue sclera
  10. What two conditions present with a cherry red macula?
    • Tay sachs
    • Niemanpieck
  11. Dysostosis multiplex?
    Abnormal Cartilage
  12. Macrophages with crinkled paper tissue appearance result in what disease?
  13. Prostoglandins, leukotrienes and thromboxanes are all derived from what fatty acid?
    Eicosanoids(arachidonic acid)
  14. Homocystonuria deficiency?
    • cyntathionine beta synthase (Vit B6--pyridoxal phosphate)
    • methionine synthase( folate, Vit B 12)
  15. Which condition's symptoms resemble that of Marfan's?
  16. Supplementation of vitamins in Homocystonuria is done for what purpose?
    To prevent thrombogenicity
  17. Whats deficient if Maple syrup disease?
    branched chain alpha keto acid dehydrogenase
  18. What a.a are not broken down in Maple Syrup Disease?
    Leucine, Isoleucine, Valine
  19. Which condition is "thiamine responsive"?
    Maple Syrup Disease
  20. Lesch-Nyhan syndrome is caused by a deficiency of what enzyme?
  21. What is produced in excess in Lesch-Nyhan Syndrome?
    Uric acid causing self mutilation, aggression,
  22. Alpha 1 antitrypsin belongs to what family of protease inhibitors?
  23. A deficiency of Alpha 1 antitrypsin causes what?
  24. Whats an example of an ecogenetic disorder?
    Alpha 1 antitrypsin
  25. Alpha 1 antitrypsin causes damage in what two organs?
    Liver and Lungs
  26. Nicotine oxidizes what a.a in the alpha 1 antitrypsin?
    methionine at 358
  27. Acute intermittent porphyria is caused by a deficiency of what enzyme?
    Porphobilinogen deaminase
  28. Why would events that induce cytochrome p 450 precipitate symptoms of acute inter
  29. Xanthoma
    cholesterol in skin
  30. Atheroma
    cholesterol in arteries
  31. What is the cause of Hyperlipoproteinemia Type IIa?
    Deficient LDL receptor
  32. Beta lipoprotein is what?
  33. Alpha lipoprotein is ?
  34. What makes up LDL?
    cholesterol and cholesteroyl esters
  35. What is the function of VLDL?
    transport of TAG's from liver to tissues
  36. B-100 is present on what FA molecule?
  37. B-48 is a marker on what ?
  38. Causes of HyperLipoproteinemia?
    • 1. LDL receptor
    • 2. B-100 apolipoprotein
    • 3. ARH adapter protein
    • 4. PCSK9 protease
  39. Hypercholesterolemia results from what?
    • decreased or no LDL receptor
    • high cholesterol/LDL
  40. Type I Hyperchylomicronemia results from what?
    What accumulates?
    • deficient lipoprotein lipase or Apo C-II
    • TAG and Cholesterols
  41. Type IV hypertriglyceridemia results from what?
    What accumulates?
    • Hepatic overproduction of VLDL
    • Triglycerides accumulate
  42. Abeta lipoproteinemia results in what?
    Absent Apo-B100/ Apo-B48
  43. Gene mutations that cause Hyperlipoproteinemia?
    • LDL receptor
    • Apo-B100
    • ARH adaptor protein
    • PCSK-9
  44. What is the function of ARH protein?
    Anchors LDL receptor in the pit
  45. What is a cofactor for lipoprotein lipase?
  46. What enzyme catalyzes the esterification of cholesterol in HDL?
  47. What enzyme degrades TAG's in Chylomicrons an VLDL?
    Lipoprotein Lipase
  48. LDL is also called?
    beta lipoprotein
  49. A gain of mutation in the PCSK9 protease Gene results in what?
    lower LDL receptor amounts
  50. VLDL obtains Apo-c -II and Apo-E from what lipoprotein?
  51. Transposition is responsible for what cholesterol disorder?
  52. Pre beta lipoprotein is what?
  53. Apo-B48 is needed for what?
    To leave the intestinal cell
  54. Chylomicrons acquire what from HDL?
    Apo-C II and Apo-E
  55. Carbon,1 ,2 and 3 carry what kinds of FA?
    • 1-only saturated
    • 2--unsaturated
    • 3--sat or unsat
  56. What happens to glycerol after lipoprotein lipase creates in from the Chylomicron?
    • It goes to liver where it could
    • --enter glycolysis
    • --resynthesize TAG
  57. What happens to chylomicron remnant?
    It is absorbed by the liver
  58. What lipoproteins are translated in intestinal cells and liver?
    • intestinal cell---Apo-48
    • liver------------- Apo-48
  59. Persistent chylomicrons in the blood suggest what?
    • deficient lipoprotein lipase
    • or Apo-C II
  60. HTGL removes what?
    remaining TAG from Chylomicrons
  61. What is the problem in Niemann-Pick C?
    lysosomes cant hydrolyze cholesterol esters
  62. What does HDL do?
    picks up cholesterol from tissues
  63. What enzyme is used to trap cholesterol as cholesterol esters?
  64. HDL uses what receptor on the liver?
    scavenger B1 receptor
  65. HDL carries what cofactor that activates LCAT?
    Apo A
  66. What is exchanged between HDL and VLDL
    cholesterol for TAG and Phosphatidylcholine
  67. A1 does what in HDL
    Activates LCAT
  68. Cholesterol + macrophages make up what?
    Foam Cells
  69. HMG coA reductase transforms HMG coA to what?
  70. What is the purpose of NO in BV?
    prevents platelet sticking to endothelium
  71. Alu transposition may be responsible for what genetic diseases?
    • DMD
    • DM
    • NF1
    • FH
  72. What type of collagen is defective in Osteogenesis imperfecta?
    TYPE 1
  73. What is the mutation in Osteogenesis Imperfecta?
    Glycine is substituted by a bulky amino acid
  74. Type I of Osteogenesis Imperfecta is caused by what?
    Decrease in Type I colagen
  75. Prenatal diagnosis of Osteogenesis Imperfecta is accomplished how?
  76. Whats responsible for Trinucleotide repeat expansions?
    • Slipped mispairing during DNA replication
    • unequal crossing over
  77. Hypermutation of 5' UTR and promoter is responsible for which Trinucleotide repeat expansion disease?
    Fragile X syndrome
  78. In what disease is the trinucleotide repeat predisposes the individual for earlier onset of disease?
  79. What complexes in the ETC need iron?
  80. Severity and age of onset correlated with repeat number is characteristic of what Group of diseases?
    Trinucleotide repeat expansion diseases
  81. Myotonic Dystrophy type 2 is caused by what?
    tetranucleotide repeat expansion
  82. Example of a pleitropy disease?
  83. What organ prefers ketone bodies?
  84. The carbon skeleton left after deamination is used for what?
    • glucose
    • TCA
    • Ketone
  85. Glucogenic a.a should contribute what?
    pyruvate or any component of TCA cycle
  86. What a.a are purely ketogenic?
    leucine, lysine
  87. What is a bidirectional shuttle?
    Malate shuttle
  88. Why is ammonia present in urine
    to maintain acid -base homeostasis
  89. What a.a form glutamate via deamination?
    • Glutamine
    • arginine
    • Histidine
    • Proline
  90. What makes up Glutathione
  91. 2 amino transporters in the blood?
    • glutamine
    • alanine
  92. 2 amino groups in urea come from where?
    • ammonium
    • aspartate
  93. What a.a is involved in the formation of glycosidic bond of glycoproteins?
  94. If folic acid is deficient what may be excreted in urine?
  95. Folic acid is involved in what?
    one carbon methabolism
  96. Histamine is formed from what a.a?
  97. Decarboxylation uses what coenzyme?
    pyridoxal phosphate
  98. What gives rise to NO?
  99. Creatinine present in plasma may suggest what?
    renal failure
  100. Glycine is used for what?
    Detoxification of benzoic acid
  101. What is caused by deficiency of glycine cleavage complex?
    glycine encephalopathy
  102. What is the endogenous source of oxalate in the body?
  103. What are the 2 sulfur containing amino acids?
    • methionine
    • cysteine
  104. What is the only reaction where all Pi from ATP are liberated?
  105. Homocytynuria is caused by what?
    • cystathionine beta synthase
    • low vitamin b12
    • low tetrahydrofolate
    • deficiency of cystathionine-methyl transferase
  106. What membrane phospholipid gives rise to arachidonic acid?
    phosphatidyl choline
  107. PAPS gets its sulfate from where?
  108. How are small amounts of cyanide detoxified?
  109. Classical homocystynuria symptoms?
    • ectopia lentis
    • skeletal abnormalities
    • mental retardation
    • osteoporosis
    • arterial diseases
  110. Elevated homocysteine in pregnant women are correlated with risk of what?
    Neural tube defect
  111. What is used for one carbon transfer?
    SAM and Folate
  112. Deficiency in Maple syrup Disease?
    branched chain alpha ketoacid dehydrogenase
  113. Which disease is "thiamine responsive"
    Maple Syrup Disease
  114. Most hereditary enzymatic deficiencies are inherited in what fashion?
    autosomal recessive
  115. Musty odor is characteristic of what disorder?
  116. Albinism is inherited how?
    Multiple inheritance pattern
  117. Alkaptonuria is caused by?
    • homogenistic acid oxidase
    • dark cartilage
    • dark urine
    • part of tyrosine degradation pathway
  118. Proteins rich in what amino acids are degraded rapidly?
  119. HCL activates what enzyme?
    pepsinogen to pepsin
  120. a.a enter cells via what transporter?
    Na transporter
  121. Endopeptidase activates what?
  122. What creates a Na +gradient in the intestinal cell?
    Na+/P+ ATPase
  123. What are the only a.a that are not metabolized by liver?
    branched chain amino acids
  124. What are the 2 transporters in the kidney and intestine?
    • COAL--cysteine, ornithine, arginine, lysine
    • kidney stone bc of high cystein in urine
  125. Cystinuria
    • defective COAL transporter
    • kidney stones due to high cysteine in the urine
    • Oral Hydration
  126. Hartnup disorder symptoms?
    caused by?
    • Dementia
    • Diarhea
    • Dermatitis
    • deficiency of tryptophan
  127. Transfer of an amino group from an a.a to an alpha keto glutarate is called?
  128. What are the only 2 a.a that do not go thru transamination?
    • serine
    • threonine
  129. All transaminases require what vitamin?
    Vit B6 pyridoxal phosphate
  130. What enzyme produces free ammonium?
    Glutamate dehydrogenase
  131. What activates glutamate dehydrogenase?
  132. How is ammonia transported to the liver?
    • ammonia + glutamate= glutamine---> liver
    • ammonia + pyruvate = alanine ---> liver
  133. What is the precursor of N in the Urea cycle?
    • aspartate from glutamate
    • NH3 from glutamate
  134. Ornithine transcarbomylase deficiency?
    makes citrulline from carbamoyl phosphate and ornithine
  135. HOw much mutant mtDNA need to be present to cause disease from deletions?
  136. Mitchondrial mutations affect what systems?
    • Eye, hearing
    • GI, PNS, CNS, Cardiac, renal endocrine
  137. What is the most common mtDNA mutation
    • A to G on tRNA
    • MELAS
  138. Leber's Hereditary Optic Neuropathy symptoms
    sudden onset of blindness in young adults
  139. Alzheimers disease onset is in what age group?
    6th-9th decade of life
  140. APP?
    amyloid precursor protein
  141. APO e?
    docking of molecules to receptors
  142. What carries APO E?
    VLDL, LDL, IDL, chylomicrons
  143. Deposits of sticky peptides cause what disease?
  144. Tau protein is implicated in what disease?
  145. Tau protein in Alzeimers is in what state?
  146. beta APP is cut wrong by what protease
    gamma protease
  147. Sticky APP are found in what condition which results in plaques?
  148. Cystinuria and cause what?
    kidney stones
  149. Cystinuria is caused by malabsorption of what a.a?
    • cysteine
    • ornithine
    • arginine
    • lysine
  150. Diamino basic a.a malabsorption cause what condition?
  151. Cystynosis cause
    cysteine crystals in lysosomes
  152. Which a.a gives rise directly to ketone body?
  153. Maple syrup disease is caused by?
    deficiency of branched chain alpha keto acid dehydrogenase
  154. Symptom of Maple syrup disease?
    Burned sugar smell of urine
  155. 5 factors of dehydrogenases?
    • thiamine--b1
    • NAD--b3
    • coenzyme a -b5
    • FAD--b 2
    • Lipoic acid
  156. What enzyme converts pheneylalanine to tyrosine
    phenylalanine hydroxylase
  157. Deficiency of phenylalanine hydroxylase or tetrahydrobiopterin causes what disease?
  158. All transaminases require what coenzyme?
    vit b 6 pyridoxal phosphate
  159. Rate determining enzyme is ketone body synthesis?
    HMG coa Synthase
  160. Vitamin C is needed for what?
    • hydroxylation of lysine and proline in collagen
    • dopamne beta hydroxylase
    • iron absroption
  161. What cells are present in the adrenal medulla?
    chromafin cells
  162. What enzyme present in maloncytes converts tyrosine to DOPA?
  163. Pheomelanin is what color?
  164. Phenylketonuria is caused by what?
    • phenylalanine hydroxylase
    • tetrahydrobiopterin
  165. Reduction of dihydrobiopterin to tetrahydrobiopterin needs what?
  166. Presence of what product in urine causes phenylketonuria
    phenyl pyruvate
  167. Disorder of aromatic a.a metabolism causes what ?
    musty odor of urine
  168. Why does urine turn yellow?
    urobilinogen is oxidized by oxygen and turns yellow
  169. Tyrosinemia is caused by?
    high levels of tyrosine
  170. Albinism is caused by?
    • locus heterogeneity
    • many inheritance pattern
  171. Deficiency of what enzyme causes Albinism?
  172. Transamination of alanine produces what?
  173. Pyridoxine phosphate is needed for what product of tryptophan metablism?
    glucogenic alanine
  174. Xanthurenic acid accumulates in what condition
    • problem metabolism of tyrosine
    • pyridoxine phosphate
  175. Decarboxylation of a.a uses what a.a?
    pyridoxal phosphate--vit b 6
  176. What keeps tetrahydrobiopterin in reduced state?
  177. Argentaffinoma is a cancer of what?
    what does it produce?
    • argentaffin cells of abdominal cavity
    • produces 5HT
  178. What product is made in Argentaffinoma?
    5 Hydroxy indole acetic acid
  179. What produces NE?
    • L. cerelus
    • S. Nigra
    • Raphe nucleus
    • Basal nucleus
    • N. Accumbens
  180. Transporter defect of neutral amino acid..tryptophan causes what disease?
    • Hartnup---tryptophan---> niacin...
    • dementia
    • diarhea
    • dermatitis
  181. How is codeine activated?
    Thru what mechanism?
    • via cyt p450
    • hydroxylation
  182. Camptothecin?
    topoisomerase inhibitor
  183. Rifampin
    blocks RNA polymerase
  184. Deficiency of NADPH Oxidase causes what?
    Chronic granulomatosis
  185. Heparin blocks the synthesis of what factors?
    • 2,9,10,11
    • Protein C and Protein S
  186. Heme is degraded by what system?
    reticulo endothelial system
  187. If biliverdin reductase is absent what accumulates?
    Biliverdin---green color
  188. How is bilirubin transported?
    by binding to albumin
  189. What accepts the bilirubin from albumin in the hepatocyte?
  190. How do hepatocytes make bilirubin polar?
    by adding glucuronic acid to it via UDP glucuronyl transferase
  191. What bacterial enzyme cleaves bilirubin to urobilinogen?
    Beta glucuronidase
  192. Stercobilinogen is also known as?
  193. Normal product of Heme catabolism?
  194. Causes for prehepatic Jaundice?
    • PK
    • G6PD
    • erythroblastosis fetalis
    • Phospholipase A 2
  195. What is increased in hemolytic jaundice?
    unconjugated bilirubin
  196. Urinary Urobilinogen is increased or decreased in hemolytic jaundice?
  197. What is the deficiency in Gilbert's syndrome?
    UDP-Glucuronyl transferase
  198. Phenobarbital
  199. ALA synthase is used for what?
    UDP glucuronyl transferase is used for what?
    • ALA synthase--heme synthesis
    • UDP glucuronyl transferase---solubility of bilirubin
  200. Anticipation
    • Appearance of disease at an earlier stage
    • Huntingtons
  201. Mechanism for Tandem repeats?
    Slipped mispairing during Replication
  202. All tandem repeat diseases are maternally repeated except?
  203. WHich tandem repeat disease is caused by tetra repeat?
    Myotonic dystrophy 2
  204. Where is the tandem repeat in
    Friedrich ataxia
    Myotonic dystrophy
    Fragile x
    • coding region
    • intron
    • 3'
    • 5'
  205. Mutation in intron of 5' UTR causes what?
    decreased transcription via hypermethylation
  206. What is the hallmark of Huntington
    Insoluble aggregates
  207. Consaguinity plays a role in which disease?
    cystic fibrosis
  208. Cystic Fibrosis is on what gene?
    7 q
  209. Mutation in Cystic Fibrosis?
    deletion of phenylalanine at 508
  210. Bilateral absence of vas deferens is seen in what disease?
    Cystic Fibrosis
  211. Meconium Ileus is see in what disease?
    Cystic Fibrosis
  212. The CFTR channel has how many domains?
  213. The CFTR genotype is a good predictor of the exocrine function but not of pulmonary function
  214. What disease is Semi dominant?
    Familiar hypercholesterolemia
  215. Type IIa hypercholesterolemia is caused by?
    • defective LDL receptor
    • defective LDL uptake
  216. What are the 4 causes for Type IIA
    • LDL receptor
    • apoprotein B100
    • ARH adapter protein
    • PCSK
  217. Hypercholesterolemia is located on what gene?
  218. Gain of function of what produces Type II a Hypercholesterolemia?
  219. What mutation in PCSK9 causes lower cholesterol levels?
  220. Which scavenger receptor takes up oxidized LDL in macrophages?
    Scavenger Type A
  221. What enzyme is elevated in DMD?
    Creatine kinase
  222. Why would a female have DMD?
    bc of random x inactivation
  223. Osteogenesis imperfecta affects which collagen?
    Type I
  224. What is the repeating unit in collage?
  225. What are the 2 types of Osteogenesis Imperfecta?
    • Type I--decreased amount of collagen
    • Type -2----a.a substitution
  226. WhAT Are the 3 proteins in which a mutation may cause Alzeimers?
    • Amyloid precursor protein
    • presenilin1
    • presenilin 2
  227. What kind of plaques are seen in alzeimers?
    amyloid presinile plaques
  228. Which secratase produces a neurotoxic amyloid precursor protein?
    gamma secratase
  229. People with what trisome are predisposed to Alzeimers disease?
    Trisomy 21
  230. What is the relationship betwee APO E and Alzeimers?
    • risk factor
    • dose dependent
  231. Phytanic acid accumulates in what disease?
  232. Kayser Fleisher ring is seen in what disease?
  233. What is Menkes disease?
    Copper is not released from cells
  234. Elfin like facies and great interpersonal skills are present in what disease?
  235. A third copy of what in pt with downsyndrome predisposes them to Alzeihmers?
    Amyloid Precursor protein
  236. The FMR-1 gene is found in what condition?
    Fragile-X syndrome
  237. What is added to cholic acid and chenodeoxycholic acids to make them salts?
    glycine and taurine
  238. What is the rate determining step in the formation of cholic acid?
    cholesterol 7 alpha hydroxylase
  239. What inhibits cholesterol 7 alpha hydroxylase?
    What promotes its actions?
    • inhibits---cholic acid
    • promotes--cholesterol
  240. Ornithine transcarbamylase results in high levels of what?
    When does it usually present?
    • orotic acid
    • within first few days of life
  241. Squalene monooxygenase is involved in what?
    conversion of squalene to lanosterol
  242. Wolman disease is caused by?
    deficiency of breaking down of cholesterol esters
  243. Niemann-Pick C is caused by?
    failure of transport of cholesterol from lysosome to
  244. What protein is deficient in Limb Girdle Dystrophy?
    • Sarcoglycans
    • Caveolin
  245. What proteins are deficient in Congenital Muscular dystrophy?
    • Fukutin
    • Merosin
  246. What protein is deficient in Emery-Dreyfus muscular dystrophy?
  247. What are the autosomal recessive muscular dystrophies?
    • Limb girdle
    • Congenital
  248. What is heteroplasmy?
    more than one copy of a genome is a cell or individual
  249. What are the 3 types of mutations in mtDNA?
    • missense
    • point mutations
    • rearrangements
  250. What kind of mutation causes Pearson and Kearns syndrome?
  251. MELAS is caused by a mutation where?
  252. Chronic progressive external Opthalmoplegia is caused by what type of mutation?
    Nuclear DNA
Card Set
Genetics Block 3
Genetics Block 3