HB-1 Exam 2 Flashcards-Week 2.txt

  1. In gout, what type of crystals build up in and around the joints?
    Monosodium urate monohydrate crystals
  2. What are some characteristics of gout?
    hyperuricemia, recurrent arthritic attacks with the presence of MSU crystals inside synovial leukocytes, MSU in and around joints, renal disease, uric acid nephrolithiasis
  3. What is the concentration where human serum is saturated with uruc acid?
    6.8 mg/dl
  4. T/F. Uric acid varies with age, gender, and diet.
    True! The older you get, the higher your uric acid. Woman get it after menopause (50s) and men will get it in their 30s and 40s. Diet high in purines can contribute (meat, shrimp, animal tissues)
  5. What are the three clinical stages of gout?
    1. acute gouty arthritis, 2. intermittant, intercritical, or interval gout, 3. Chronic gouty arthritis
  6. What are ways to make a definitive diagnosis of gout?
    -Identification of MSU crystals in synovial fluid leukocytes-Identification of monosodium urate crystals from a tophus
  7. What is the purpose of synovial fluid?
    lubricant and adhesive, nutrients for cartilage
  8. What do you do with the synovial fluid?
    Observe gross appearance, order cell count, order culture and gram stain, order crystal analysis (fresh unstained wet sediment)
  9. What are the crystals in pseudogout?
    Calcium pyrophosphate
  10. What are the characteristics of normal synovial fluid?
    Transparent clear or light yellow, slightly viscous, WBCs low with few or no RBCs, low percentage of neutrophils, glc similar to plasma, no crystals, neg. culture
  11. What are the characteristics of gout fluid?
    Turbid opaque fluid, WBC count between 10,000-50,000 (most neutrophils), negative culture and gram stain, MSU crystals (5-20 um needle shaped, negatively birefringent-yellow when parallel to compensator, blue when perpendicular)
  12. What are other factors that can contribute to gout?
    Hypertension, thiazide (loop diuretics), obesity, high alcohol intake, high meat intake, hyperinsulinemia, metabolic syndrome
  13. What are some possible treatments for gout?
    1. hypoxanthine to xanthine pathway inhibitors 2. xanthine to uric acid pathway inhibitors 3. diet low in purines 4. regulate genes (SLC2A9) responsible for uric acid exretion 5. slighly modify pH of blood-higher pH favors solubility
  14. How much oxidative energy requirement for the liver, kidneys, heart, and resting skeletal muscle comes from fatty acid oxidation?
  15. In general, what are the steps of lipid metabolism?
    1. TAGs hydrolyzed in adipose tissue to fatty acids plus glycerol (via lipases) 2. Transport of fatty acids in blood to the tissues 3. Activation of fatty acids as a CoA ester 4. Transport into mitochondria via carnitine shuttle 5. Metabolism to acetyl CoA
  16. Where do we get the fat that we burn?
    Diet, liver, adipose, blood, muscle (more in trained)
  17. How are fats from the diet transported?
  18. How are TAGs from the liver transported?
  19. How are free fatty acids released from adipose tissue carried in the blood?
    Use plasma albumin
  20. What hormones can trigger lipolysis? What pathway do they activate?
    Adrenaline, glucagon, and ACTH---activate cAMP, which activates the lipase
  21. Fats are the major source of energy for all human tissues except what two things?
    RBCs and brain
  22. What are the two 'oxidative machines'?
    mitochondira and peroxisomes
  23. How do fatty acids come into the mitochondria?
    Acyl CoA synthetase on the outer mito membrane turns a fatty acid into an acylCoA, which can cross the outer mito membrane. The carnitine acyltransferase I (also in OMM) turns the acylCoA into acylcarnitine. The acylcarnitine crosses the IMM with the help of carnitine acylcarnitine transferase. Once in the mito matric, carnitine acyltransferase II turns the acyl carnitine back into acylCoA.
  24. What number of carbons are considered a long chain fatty acid? Where does the catabolism take place? Very long chain?
    Long chain fatty acids are 12-20 carbons. Their catabolism occurs in the mitochondria via the carnitine shuttle. The very long chain fatty acids are greater than 20 carbons and are broken down in the peroxisome.
  25. Beta oxidation is the same for odd # fatty acid chains as it is for even until the final 3 carbons. What happens to the propionyl CoA?
    Propionyl CoA is converted to methylmalonyl CoA (by adding a CO2, uses biotin and ATP). methylmalonyl CoA is converted to succinyl CoA by methylmalonyl CoA mutase (uses coenzyme form of B12).
  26. What is methylmalonic acidemia? Methylmalonic aciduria?
    Acidemia: mutase missing (can't convert methylmalonyl CoA to succinyl CoA). Aciduria: unable to convert vitamin B12 to coenzyme form. They both block the same step and result in metabolic acidosis and developmental retardation.
  27. What type of oxidation do branched fatty acids use? Where does this occur?
    alpha oxidation because beta site is inaccessible. peroxisomes
  28. Is malonyl CoA an activator or inhibitor of the carnitine shuttle?
    Inhibitor! It inhibits carnitine acyltransferase I and blocks entry of acyl groups into mito.
  29. In case of starvation, the liver can convert excess acetyl CoA into what?
    Ketone bodies. Made from HMG CoA (like cholesterol) HMG CoA lyase makes acetoacetate from HMG CoA. This acetoacetate can then make acetone or 3-hydroxybutyrate
  30. What is Jamaican vomiting sickness?
    Caused by unripe fuit which contains a toxin, hypoglycin, which inhibits medium and short chain acyl CoA dehydrogenases (inhibits B oxidation)
  31. What is the result of carnitine deficiency?
    muscle aches and weakness following exercise, elevated blood free fatty acids. nonketotic hypoglycemia because gluconeogenesis cannot be suuported by fat oxidation
  32. What is Zellweger syndrome?
    absence of peroxisomes in the liver and kidneys leads to accumulation of very long chain fatty acids in the brain
  33. Inborn errors of metabolism are often what two types of inheritance?
    autosomal recessive and X linked
  34. PKU is a deficiency of what enzyme? What are the consequences? What other enzyme deficiency can produce the same symptoms?
    PKU: phenylalanine hydroxylase deficiency, causes a build up of Phe that can't be converted to Tyrosine and also causes a buildup of toxic metabolites (2-hydroxyphenylacetic acid, phenylpyruvic acid, phenyllactic acid)--deficiency of dihydropteridine reductase (produces the cofactor for Phe phydroxylase) can give same symptoms
  35. What are the molecular bases of enzyme deficiency?
    -dysfunctional protein (hypomorphic mutation), no enzyme synthesized (null mutation), deficient co-factor processing, biotinidase deficiency, deficient activator protein, defective trans acting factor (transcription factor)
  36. What is the function of biotinidase?
    Used to convert biocytin into free biotin, which is used in many carboxylase reactions
  37. What are the standards of diagnosis?
    1. Metabolite pattern for enzyme deficiency 2. Demonstrate enzyme deficiency 3. Demonstrate mutation in gene
  38. What are some laboratory blood tests for preliminary diagnosis of inborn metabolism errors?
    Serum amino acids, ammonia, glc, lactate, acylcarnitine (blood, serum, bile), blood cell enzyme assays, DNA analysis
  39. What are some laboratory urine tests for preliminary diagnosis of inborn metabolism errors?
    amino acids, organic acids, acylcarnitines, glycosaminoglycans
  40. What are the general concepts of therapy for inborn errors of metabolism?
    1. Remove the cause 2. Remove the toxicity 3. Supply the missing product
  41. What are the general clinical signs of inborn errors of metabolism?
    failure to thrive, dysmorphology, acute, episodic disease, unusual odors, chronic, progressive disease
  42. What are the biochemical/molecular genetic approach to diagnosis?
    Metabolite profile, demonstrate enzyme deficiency, and demonstrate mutation
  43. What are some characteristics of diseases with decifient fatty acid oxidation?
    Severe hypoglycemia/poor ketogenesis, sudden infant death, exercise intolerance, heart disease, fatty liver, severe illness (HELLP, AFLP) late in pregnancy
  44. What is the transcription factor responsible for the regulation of fatty acid oxidation and how is it activated?
    PPAR is activated by the binding of ligands, FA, and fibrates. PPAR forms a complex with RXR and this recruits coactivators. Gene transcription for fatty acid transport and oxidation increases.
  45. The mitochondrial trifunctional protein is made of what two subunits?
    HADHA-alpha subunit=enoyl CoA hydratase/LCHAD activity and HADHB-beta subunit=ketoacyl CoA thiolase activity
  46. What is HELLP? What is it caused by?
    hemolysis elevated liver enzymes, low platelets. caused by LCHAD deficiency/trifunctional protein
  47. What are some therapies for fatty acid oxidation disorders?
    Mostly nutritional, some drugs, stabilize day to day, avoid catabolic events
  48. What is the most common fatty acid oxidation disorder?
    MCAD deficiency
  49. What is the biochemical basis of clinical diagnosis of a fatty acid oxidation disorder?
    acylcarnitines and urinary organic acids
  50. What are some metabolic concepts for preventing disease episodes for a fatty acid oxidation disorder?
    -avoid fasting/exercise/catabolic stress, short chain fatty acids (bypass the block), odd chain fatty acids (anaplerotic), IV glc/fluids
  51. How are primary bile acids converted into secondary bile acids?
    by bacteria in the intestine
  52. What type of cells synthesize bile acids? How many carbons are bile acids/salts?
    synthesized in liver parenchymal cells--24 carbons
  53. What is the rate limiting enzyme of the synthesis of bile acids and what does it do?
    microsomal 7-alpha-hydroxylase (CYP7A1), which installs the OH at position 7 using P450
  54. How many grams of bile acids pass from the bile duct to the intestine each day? What percent is lost in the feces?
    30 g/2% lost
  55. How are gall stones formed?
    from bile supersaturated with cholesterol
  56. How many carbons do the steroid hormones, corticosteroids, androgens, and estrogens contain?
    C21, C19, C18
  57. What are the two types of steroid hormone receptors?
    Type 1: cytoplasmic receptors Type 2: Nuclear receptors
  58. What is the mode of action of steroid hormones binding to a cytoplasmic receptor?
    Upon steroid binding to receptor, dimerization of receptor occurs and a nuclear localization signal is exposed, complex enters nucleus and binds specific response element, or hormone response element, this functions as a sequence-specific transcription factor
  59. What is the main differences between the glucocorticoid receptor zinc finger and the standard zinc finger?
    glucocorticoid has 4 Cys (vs 2 Cys and 2 His)
  60. What is the function of zinc finger proteins?
    recognize short palindrome sequences of DNA
  61. T/F Steroid receptor protein motifs are conserved.
  62. What type of cells release insulin? glucagon?
    GABI: glucagon released by alpha cells, beta cells release insulin (both part of islets of langerhands in the pancreas)
  63. What is a good marker for beta cell function?
    C peptide! because it is equimolar to insulin conc
  64. What is the process of insulin secretion?
    Glc enters pancreatic beta cell, phosphorylated by glucokinase or hexokinase to make G6P...ultimately increases ATP which blocks the K+ channel, this depolarizes the cell and opens the Ca2+ channel. Ca2+ increase in the cell causes insulin secretion
  65. What is the second phase of insulin release?
    involves new synthesis of insulin-responds to an increase in cytosolic long acyl CoA (sign of well fed state)
  66. What amino acids stimulate insulin secretion?
    Leu, Arg, Lys
  67. What GI hormones potentiate insulin secretion?
    Glc-dependent insulinotropic (GIP), CCK, glucagon-like peptide 1 (GLP1) and vasoactive intestinal peptide (VIP)
  68. T/F Insulin response to oral glc is lower than IV infusion.
    False! Insulin response to oral glc is higher!
  69. What is the general pathway of insulin binding its receptor?
    Insulin binds its receptor, the insulin receptor phosphorylates a tyrosine kinase, which activates IRS-1...which ultimately brings GLUT 4 to the cell membrane
  70. What percent of GLUT 4 is on the membrane?
  71. What are the three main target tissues that insulin acts upon?
    Liver, adipose, skeletal muscle
  72. Epinephrine stimulates what in muscle? in liver?
    Glycolysis!, muscle has no G6Pase and can't release free glc...in the liver epi decreases glycolysis (increases gluconeogenesis)
  73. What two tissues use the GLUT 4 transporter? Is this insulin dependent or independent?
    adipose and muscle, insulin dependent
  74. What 3 things use GLUT2 glucose transporter? Insulin dependent or independent?
    liver, beta cells, intesitnal epithelial cells--insulin independent
  75. What decreases the expression of GLUT 4 in the muscle?
    fatty acids
  76. What are the most impt causes of insulin resistance in type 2 diabetics?
    1. defective insulin signaling 2. decreased # or affinity of insulin receptors 3. insulin receptor antibodies
  77. What is the structure of fork-head transcription factors?
    winged helices
  78. What is Foxo1?
    promotes gluconeogenesis by inducing genes for PEPCK and G6Pase. insulin phosphorylates Foxo1 and inhibits gluconeogenesis
  79. What is Foxa2?
    regulates fatty acid oxidation by inducing enzymes of glycolysis, FA oxidation, and ketogenesis. insulin phosphorylates foxa2, which inhibits fatty acid oxidation
  80. What are the main characteristics of diabetes and long term effects?
    hyperglycemia resulting from defects in insulin secretion, insulin action, or both. diabetic retinopathy, nephropathy, neuropathy, atherosclerosis, hypertension, cardio and cerebrocascular disease
  81. What is a healthy person's fasting blood glucose? pre-diabetic? diabetic?
    100, 1000-125, >125 mg/dl
  82. What are the glucose levels of a oral glucose tolerance test for a normal person? pre-diabetic? diabetic?
    120-140, 140-199, >200 mg/dl
  83. What is the effect of high blood glucose and cellular fluid?
    high osmotic pressure in ECF, causing cellular dehydration. xs glc lost in urine (glycosuria)
  84. What is the effect on the kidney of glycosuria?
    excessive glc in the kidney filtrate acts as an osmotic diuretic, inhibiting water reabsorption, resulting in polyuria, decreased blood volume, and dehydration (causes polydipsia)
  85. T/F Dehydration can cause blurred vision in diabetic pts because of fluctuations in the amount of glc and water in the lenses of the eye
  86. What is polyphagia?
    xs hunger and food consumption. this is because even though glc is available, it cannot be used and cells begin to starve
  87. In diabetes, what is a major source of energy?
    free fatty acids and later, ketone bodies---in all tissues except the brain
  88. What are the complications of ketosis?
    electrolyte losses, neg charge of ketone bodies carries out Na+ and K+ with it, because of electrolyte imbalance, pt will have abdominal pains and main vomit
  89. What is the most common cause of death in pts with diabetes?
    Myocardial infarction
  90. What occurs in non-proliferative retinopathy?
    blood vessels in the retina leak and hemorrhage. macula edema is the most common cause of visual loss in diabetic retinopathy
  91. What is proliferative retinopathy?
    new blood vessels grow in the eye, leading to bleeding and leaking causing vision loss. they can also pull on the retina causing retinal detachment
  92. What are the consequences of high blood glucose in the mouth?
    Gingivitis and periodontitis
  93. What are the effects of diabetes on nerves?
    numbness and tingling in feed, night leg cramps, loss of ability to feel pain in the feet, leading to ulceration
  94. What is glucose tolerance?
    the body's ability to manage its blood sugar level within normal range. (uses Cori cycle)
  95. T/F. Brain cells only use glc for energy. What are the consequences of glc levels on the brain?
    True. When glc is low, hypoglycemic shock develops, nervous irritability leading to fainting, seizures, and coma
  96. What is fluoxetine? What is it used to treat?
    Selective serotonic reuptake inhibitor (SSRI), used to treat major depression, obsessive compulsive disorder
  97. What is the 1st step in metabolizing fluoxetine?
    demethylating it to norfluoxitine. this occurs in the liver by CYP2D6 pathway
  98. What is methylphenidate?
    psycho-stimulant used to treat ADD, increases levels of dopamine in the brain through reuptake inhibition. this increases signal strength in target neurons
Card Set
HB-1 Exam 2 Flashcards-Week 2.txt
HB1 exam 2, week 2