Step 1 Biochem

  1. Orotic aciduria defect
    • Either orotic acid phosphoribosyltransferase or orotidine 5'-phosphate decarboxylase
    • defect in orotic acid --> UMP (pyrimidine synthesis)
  2. Orotic aciduria findings
    • Increased orotic acid in urine
    • megaloblastic anemia not improving with B12 or folic acid
    • FTT
  3. Ornitine Transcarbamoylase (OTC) deficiency findings
    increased urine orotic acid WITH hyperammonemia
  4. Purine salvage deficiencies
    • Adenosine deaminase deficiency
    • Lesch-Nyhan syndrome
  5. Adenosine deaminase deficiency causes:
    • Excess ATP and dATP feedback inhibit ribonucleotide reductase
    • Lymphocyte count dives. Can cause SCID
  6. What is Lesch-Nyhan syndrome?
    • Defective purine salvage from XLR absence of HGPRT
    • HGPRT normally converts hypoxanthine --> IMP and guanine --> GMP
    • Excess uric acid production causing retardation, self-mutilation, hyperuricemia, gout
  7. What can somebody with xeroderma pigmentosum not do?
    Repair thymidine dimers (nucleotide Xcision repair)
  8. Where is alpha-amanitin found and why is it bad for you?
    In death cap mushrooms; inhibits RNA polymerase II and kills your liver
  9. What fails in I-cell disease?
    • The addition of mannose-6-phosphate to lysosome proteins.
    • Coarse facial features, clouded corneas, stiff joints
  10. What is defective in Chediak-Higashi syndrome?
    Microtubule polymerization. Decreased ability to phagocytose pyogenic infections.
  11. What is defective in Ehlers-Danlos?
    Type III collagen (cross-linking)
  12. What's the defect in osteogenesis imperfecta and which type of OI is worse?
    Type 1 collagen (glycosylation)? Type II OI is fatal early.
  13. Blotting procedures, compass-style:
    • Southern: DNA (DNA probe)
    • Northern: RNA (DNA probe)
    • Western: Protein (Antibody probe)
  14. What is pliotropy?
    1 gene has more than 1 effect on a person's phenotype
  15. What is locus heterogeneity?
    When a trait has several potential genetic causes, e.g. marfanoid habitus or albinism
  16. Achondroplasia mutation
    FGF receptor 3
  17. Autsomal-dominant polycystic kidney disease mutation and associated problems
    • APKD1 on chromosome 16; 16 letters in polycystic kidney
    • Polycystic liver, berry aneurysms, mitral valve prolapse
  18. Familial adenomatous polyposis mutation
    APC gene on chromosome 5. 5 letters in polyp
  19. What findings are there in hereditary hemorrhagic telangiectasia (AKA Osler-Weber-Rendu syndrome)?
    Telangiectasia, recurrent epistaxis, skin discolorations, AVMs. It's a disorder of BVs.
  20. What repeats and on what gene for Huntington's disease?
    CAG repeats on chromosome 4. (Decreased GABA and ACh)
  21. Findings and chromosome for NF-1
    cafe-au-lait spots, neural tumors, Lisch nodules (iris hemartomas), scoliosis, optic gliomas, pheo. Chromosome 17.
  22. Findings in NF-2 and chromosome
    Bilateral acoustic neuroma, juvenile cataracts. Chromosome 22
  23. What is tuberous sclerosis?
    • Facial lesions, ash leaf spots on skin, cortical/retinal hamartomas, seizures, MR, renal cyts and angiomyoliposmas, cardiac rhabdomyomas, astrocytomas.
    • There is incomplete penetrance with a variable presentation.
  24. Von Hippel-Lindau disease: gene and findings
    • VHL gene (tumor suppressor) deletion on chromosome 3 causes expression of HIF (a TF) and angiogenic growth factor activation.
    • Bilateral RCC, hemangioblastomas.
  25. Genetic problem in Fragile X syndrome
    CGG trinucleotide repeats on the X chromosome affecting methylation/expression of FMR1 gene.
  26. Genetic problem in myotonic dystrophy
    CTG repeats
  27. What is Edwards' syndrome?
    • Trisomy 18
    • Specific findings: micrognathia, low-set ears, clenched hands
  28. What is Patau's syndrome?
    • Trisomy 13
    • Specific findings: microphthalmia, microcephaly, cleft lip/Palate, holoProsencephaly, Polydactyly
  29. Cri-du-chat gene and findings
    • Microdeletion of short arm of chromosome 5
    • High pitched crying, epicanthal folds, cardiac abnormalities
  30. Williams syndrome gene and findings
    • Microdeletion of chromosome 7, including elastin gene
    • Elfin facies, MR, hypercalcemia due to increased sensitivity to vitamin D, extreme friendliness
  31. DiGeorge syndrome, gene and embryological defect
    • Microdeletion at 22
    • Cleft palate, Abnormal facies, Thymic aplasia, Cardiac defects, Hypocalcemia 2/2 parathyroid aplasia
    • Abberant development of 3rd and 4th branchial pouches
  32. B2 alternate name
  33. B3 alternate name
  34. B5 alternate name
    pantothenic acid/CoA
  35. B6 alternate name
  36. B12 alternate name
  37. Deficiency of B1/thiamine
    ATP depletion, Wernicke-Korsakoff, beriberi
  38. Beriberi, symptoms of both types
    Polyneuritis, muscle wasting, high-output cardiac failure, adema
  39. Thiamine is a cofactor for these enzymes
    • pyruvate DH (glycolysis)
    • alpha-KG DH (TCA cycle)
    • transketolase (HMP shunt)
    • branched-chain AA DH
  40. B2/riboflavin deficiency
    Cheilosis (lips, mouth) and Corneal vascularization
  41. B3/niacin is derived from ____ and requires ___ for synthesis
    Tryptophan, B6/pyridoxine
  42. B3/niacin deficiency
    Pellagra: Diarrhea, Dermititis, Dementia
  43. Conditions causing niacin deficiency
    • Hartnup disease (decreased tryptophan absorption)
    • Malignant carcinoid syndrome (increased tryp metabolism
    • INH treatment (decreases B6)
  44. B5/pantothenate function and deficiency
    • Component of CoA and fatty acid synthase
    • Dermatitis, enteritis, alopecia, adrenal insufficiency
  45. B6/pyridoxine function and deficiency
    • Used in transamination (ALT/AST) decarboxylation reactions, glycogeno phosphorylase, cystathionine synthesis, heme synthesis, niacin synthesis.
    • Convulsions, hyperirritability, peripheral neuropathy, sideroblastic anemias
    • INH and OCPs can induce deficiency
  46. B12/cobalamin function
    • cofactor for homocysteine methyltransferase and mehtylmalonyl-CoA mutase
    • In other words, helps create methionine for the creation of dUMP from dTMP
    • and helps create succinyl-CoA
  47. How folic acid deficiency is different from B12 deficiency
    No neurological symptoms, but still a megaloblastic anemia
  48. What does S-adenosyl-methionine do?
    • Transfers methyl units.
    • Required to convert NE to epi.
    • Made from methionine, which requires B12 and folate
  49. Biotin is a cofactor for these carboxylation enzymes
    • Pyruvate carboxylase (pyruvate to oxaloacetate)
    • Acetyl-CoA carboxylase (acetyl-CoA to malonyl-CoA)
    • Propionyl-CoA carboxylase (propionyl-CoA to methylmalonyl-CoA)
  50. Vitamin C functions
    • Facilitates iron absorption (keeps iron reduced to Fe2+)
    • Hydroxylattion of proline and lysine for collagen
    • Required for dopamine beta-hydroxylase
  51. What form of vitamin D is the active form?
    1,25-(OH)2D3 (Calcitrol)
  52. Vitamin D's affect on calcium and PTH
    Increases serum Ca and suppresses PTH
  53. Vitamin E deficiency
    hemolytic anemia, muscle weakness, neurodysfunction
  54. Zinc deficiency
    delayed wound healing, hypogonadism, decreased adult hair, dysgeusia, anosmia
  55. Disulfiram inhibits this enzyme in this cell compartment
    Acetaldehyde dehyrdogenase in the mitochondria
  56. Ethanol's metabolic effects
    • Increases the ratio of NADH/NAD+ in the liver
    • Gluconeogenesis is inhibited and fatty acid synthesis is stimulated
    • (Causes pyruvate to lactate and OAA to malate)
  57. Processes occuring in the mitochondria
    • FA oxidation
    • acetyl-CoA production
    • TCA cycle
    • Oxidative phosphorylation
    • (Heme synth, Urea cycle, Gluconeogenesis)
  58. Processes occuring in the cytoplasm
    • Glycolysis
    • FA syntehsis
    • HMP shunt
    • Protein synthesis
    • Steroid syntehsis (SER)
    • (Heme synth, Urea cycle, Gluconeogenesis)
  59. Rate-determining enzymes for glycolysis and gluconeogenesis
    • PFK-1
    • Fructose-1,6-bisphosphatase
    • (F-6-P <--> F-1,6-BP)
  60. Rate determining enzyme for TCA cycle
    • Isocitrate DH
    • isocitrate to alpha-KG
  61. Rate-determining enzyme for glycogenolysis
    Glycogen phosphorylase
  62. Rate-determining enzyme for fatty acid syntehsis
    Acetyl-CoA carboxylase
  63. Rate-determining enzyme for fatty acid oxidation
    Carnitine acyltransferase I
  64. Hexokinase: action and personality
    • Phosphorylates glucose
    • Ubiquitous, high affinity (low Km), low capacity (low Vmax)
    • Doesn't care if insulin is around
  65. Glucokinase, action and personality
    • Phosphorylates glucose
    • Low affinity (high Km), high capacity (high vmax).
    • Found in liver and beta cells of pancreas.
    • GLUtton: cannot be satisfied or inhibited. induced by insulin
  66. Glycolytic enzymes that ATP inhibits
    • PFK-1
    • Pyruvate kinase
    • Pyruvate dehydrogenase
  67. high levels of acetyl-CoA inhibit this glycolytic enzyme
    Pyruvate dehydrogenase (pyruvate to acetyl-CoA)
  68. High levels of alanine inhibit this glycolytic enzyme
    Pyruvate kinase (PEP to pyruvate)
  69. High levels of citrate inhibit this glycolytic enzyme
    PFK-1 (F6P to F1,6BP)
  70. Deficiency in pyruvate kinase or phosphoglucose isomerase causes this
    Hemolytic anemia (RBC swelling and lysis from pump failure)
  71. Cofactors required for pyruvate DH complex and alpha-KG DH
    • B1
    • B2
    • B3
    • B5
    • Lipoic acid
  72. Arsenic inhibits this
    lipoic acid (pyruvate DH complex)
  73. Arsenic poisoning
    Vomiting, rice water stools, garlic breath
  74. Pyruvate kinase creates
    pyruvate (created by)
  75. Pyruvate dehydrogenase creates
    acetyl-CoA (created by)
  76. Pyruvate dehydrogenase deficiency
    • Lactic acidosis, neurological defects
    • Congenital or from B1 deficiency
    • Tx: Lysine and Leucine, the only purely ketogenic amino acids
  77. Things you can do with pyruvate
    • 1. make alanine to carry amino group to liver
    • 2. make OAA for TCA or gluconeogenesis
    • 3. transition from glycolysis to TCA cycle
    • 4. make lactate
  78. Poisons causing a drop in proton gradient and block of ATP syntehsis
    Rotenone, CN-, antimycin A, CO
  79. Poison inhibiting mitochondrial ATPase, increasing proton gradient
  80. Things uncoupling oxphosph by increasing membrane permeability and decreasing the proton gradient
    2,4-DNP, aspirin, brown fat
  81. Irreversible enzymes of gluconeogenesis
    • Pyruvate carboxylase (pyruvate to OAA)
    • PEP carboxykinase (OAA to PEP)
    • Fructose-1,6-bisphosphatase (makes F6P)
    • Glucose-6-phosphatase (makes glucose)
  82. Problem in G6PD deficiency
    inadequate NADPH to reduce glutathione
  83. Smear findings for G6PD deficiency
    • Heinz bodies (oxidized hemmoglobin in RBCs)
    • Bite cells (removal of heinz bodies by macrophages)
  84. Aldolase B deficiency
    • Same as Fructose-1-phosphate aldolase
    • F-1-P accumulates, decreasing phosphate, inhibiting glycogenolysis and gluconeogenesis
    • hypoglycemia, jaundice, cirrhosis, vomiting
  85. Fructokinase deficiency
    • Essential fructosuria. Benign.
    • Fructose in blood and urine
  86. Galactose-1-phsophate uridyltransferase deficiency
    • Galactitol accumulates
    • FTT, jaundice, hepatomegaly, cataracts
  87. Galactokinase deficiency
    • Galactitol accumulates if galactose is in diet. mild.
    • Galactose in blood and urine, cataracts.
  88. Sorbitol dehydrogenase function
    Convert sorbitol to fructose
  89. Essential amino acids
    • Val
    • Arg
    • His
    • Ile
    • Leu
    • Lys
    • Phe
    • Thr
    • Trp
  90. Maple syrup urine disease
    Deficiency in alpha-ketoacid dehydrogenase, which requires thiamine
  91. Glucose-6-phosphatase deficiency
    • von Gierke's disease
    • hypoglycemia, glycogen in liver, high lactate, hepatomegaly
  92. Lysosomal alpha-1,4-glucosidase
    • Pompe's disease
    • Cardiomegaly
  93. Debranching enzyme (alpha-1,6-glucosidase)
    Cori's disease. Milder von Gierke's with normal lactate
  94. Skeletal muscle glycogen phosphorylase
    • McArdle's disease
    • Muscle cramps, myoglobinuria
  95. alpha-galactosidase A deficiency
    • Fabry's
    • Ceramide trihexoside accumulates
    • Peripheral neuropathy, angiokeratomas, CV/renal dz
  96. beta-glucocerebrosidase deficiency
    • Gaucher's
    • Glucocerebroside accumulates
    • hepatosplenomegaly, aseptic necrosis of femur, tissue paper macrophages
  97. Sphingomyelinase deficiency
    • Niemann-Pick
    • Sphingomyelin accumulates
    • Foam cells, cherry-red spot
  98. Hexosaminidase A deficiency
    • Tay-Sachs
    • GM2 ganglioside accumulates
    • No hepatosplenomegaly (vs. niemann pick)
  99. Galactocerebrosidase deficiency
    • Krabbe's
    • Galactocerebroside accumulates
    • neruopathy, DD, optic atrophy, globoid cells
  100. Arylsulfatase A deficiency
    • Metachromatic leukodystrophy
    • Cerebrosid sulfate accumulates
    • Ataxia, dementia (demyelination)
  101. alpha-L-iduronidase deficiency
    • Hurler's
    • Heparan and dermatan sulfate accumulate
    • DD, gargoylism, corneal clouding, hepatosplenomegaly
  102. Iduronate sulfatase deficiency
    • Hunter's syndrome
    • Heparan and dermatan sulfate accumulate
    • Mild Hurler's plus aggression. No corneal clouding
  103. Citrate shuttle
    puts Acetyl-CoA into cytoplasm for FA synthesis
  104. Carnitine shuttle
    Puts acyl-CoA into mitochondria for beta-oxydation
  105. Carnitine deficiency
    • Can't transport LCFAs into mitochondria
    • Wekness, hypotonia, hypoketotic hypoglycemia
  106. lipoprotein A-I
    activates LCAT to esterify cholesterol
  107. lipoprotein B-100
    binds LDL receptor, mediates VLDL secretion
  108. lipoprotein C-II
    Cofactor for lipoprotein lipase, which degrades chylomicrons
  109. lipoprotein B-48
    mediates CM secretion from intestine
  110. lipoprotein E
    mediates Extra remnant uptaet
  111. B-100 and B-48 deficiency
    • Abetalipoproteinemia: no CM secretion from intestine
    • FTT, steatorrhea, acanthocytosis, ataxia, night blindness
Card Set
Step 1 Biochem
USMLE Biochem from FA