HB1- exam 2 note cards grabbag.txt

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HB1- exam 2 note cards grabbag.txt
2010-09-25 18:55:48
hb1 exam2 gouty tophus

random gems, hb1, exam 2
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  1. Cholesterol
    steriod ring system, an important part of membrane integrity, provides carbon platform with messages above and below rings (methyl or hydroxyl groups)
  2. Cholesterol absorption/transport
    After absorption in the gut, transported to liver and tissues via chylomicrons
  3. Bile salts
    cholesterol is broken down into bile salts by hydroxylases, excreted form of cholesterol
  4. Bile acids
    return to the liver after reabsorption in the terminal ileum, recycled form of cholesterol
  5. Cholesterol biosynthesis
    humans can synthesize up to 1g cholesterol per day
  6. Cholesterol ester
    most cholesterol is stored as esters because you can store fatty acids on them, transported via lipoprotein
  7. Chylomicrons
    water soluble, fat glob, apolipoproteins on surface allow for cell recogniton, cholesterol ester, free fatty acids, triglycerides in the core
  8. Biosynthesis of 1 mole of cholesterol
    18 moles of aceytl CoA, 36 moles of ATP, 16 moles of NADPH
  9. Site of cholesterol biosynthesis
    cytoplasm of hepatic liver cells, starts wth acetyl CoA
  10. Cholesteor biosynthesis pathway
    Acetyl CoA (2C)--(HMG CoA reductase)-->mevalonate (6C)--->farnesyl pyrophosphate( 15 C)---> combine 2 farnesyl--->squalene (30C)--->7-dehydro-cholesterol
  11. Rate limiting enzyme for cholesterol biosynthesis
    HMG CoA reductase-->takes ester and reduces it down to an alcohol (mevalonate) **IRREVERSIBLE
  12. HMG CoA reductase activity
    Phosphorylated is inactive and non-phosphorylated is active
  13. Synthesis of HMG CoA reductase
    Hepatic HMG CoA reductase synthetase--> stimulated by well fed state, inhibited by dietary cholesterol intake
  14. Statin drugs
    inhibit HMG-CoA reductase to prevent cholesterol biosynthesis-->lower intracellular cholesterol and lowers apo B/E recpetor
  15. ACAT
    turns cholecterol in cholesterol ester
  16. Regulation of cholesterol uptake via SREBP
    Oxysterols (hydroxylated cholexterol) bind to Liver X receptor (LXR)-->upregulates SREBPs-->SCAP bring SREBP to protease-->cleaved by protease-->activates SREBP in gene expression
  17. Factors that increase intracellular cholesterol concentration
    de novo biosynthesis, Hydrolysis of cholesterol esters (cleave esters), Dietary intake of cholesterol and uptake from chylomicrons, receptor mediated uptake of cholesterol containing lipoproteins (LDL)
  18. Factors decreasing intracellular cholesterol concentration
    Inhibition of cholesterol biosynthesis, Downregulate the LDL receptor, Esterification of cholesterol by acyl-CoA, Release of cholesterol to HDL, Conversion of cholesterol to bile salts or steroid hormones
  19. Hormone activation of cholesterol biosynthesis
    insulin and tri-iodo-->increases cholesterol biosynthesis, glucagon and cortisol-->decrease cholesterol biosynthesis
  20. Steroid hormones (3 classes)
    C21 corticoids in adrenal cortex, C19 androgens in testis, C18 estrogens in ovary
  21. Steroid hormones in cell
    penetrate plasma membrane, bind to cytoplasmic locasted receptors-->causes conformational change in transcription factors
  22. Polypeptides hormones in cell
    can't cross plasma membrane->bind to cell surface receptor-->termed first messengers-->intracellualr effects are mediated by small molecules like cAMP
  23. Nitric oxide (NO)
    vasodilator used for angina, nitro pakcets are nitrated glycerol molecules-->signal the relaxation of smooth muscle in blood vessels by stimulation of guanylate cyclase= changes in intracelluar Ca2+
  24. Phospholipase (PLA2)
    cleaves specific phospholipis to generate lipids messengers (arachidonic acid, DAG)
  25. Arachidonic acid
    C20 unsaturdated fatty acid-->lipid 2nd messenger or inflammatory messenger
  26. Eicsanoids
    synthesized in membranes from AA, signal via G-protein receptors, made via COX1 and COX2 enzymes
  27. Leukotrienes
    Made from AA via lipoxygenases, have roles in inflammation
  28. PLA2
    cleaves DAG or phospholipid-->arachodonic acid
  29. COX1 and COX2
    use arachodonic acid make prostaglandins thromboxane, prostacyclin
  30. lipoxygenase
    use arachodonic acid make leukotrienes
  31. cytochrome P450
    use arachodonic acid make HETE (CO/NO inhibit here)
  32. Prostaglandin synthesis
    start with AA --> make PGG2--> use peroxidase to make PGH2
  33. Thromboxane
  34. Prostacycline
  35. Prostaglandins
    Fever inducers (COX1 and COX2 convert AA to PGG2)
  36. NSAIDS
    non selective COX inhibitors (aspiring, ibuprofen), block COX1 and COX2-->inhibits the synthesis of PGG2 from AA)
  37. Aspirin mode of action
    irreversibly acetylates COX1 and COX2, reduces inflammation, blocks the production of thromboxane (vasoconstrictor and clot builder)
  38. Prednisone
    Steroidal anti-inflammatory drugs, inhibit PLA2, block all eicosanoids from converting DAG and phospholipids---> Arachodonic acid
  39. Leukotrienes
    type of eicosanoid not made form COX1 and COX2, inflammatory/vasoactive mediators, made from AA via the action of lipoxygenases (which add O to lipid chains)
  40. Deficiency in lipoxygenases
    40% of myeloproliferative disorders-->reduced lipoxygenases activity and increased synthesis of thromboxane
  41. Leukotriene activation
    AA uses 5-LO and FLAP to make HPETE--> becomes LTA4 uses enzyme LTA4 hydrolase--> LTB4 (power attractant for immune cells)
  42. LTB4
    power attractant for immune cells, involved in ashmatic and allergic reactions
  43. Hypoglycemia
    blood glucose levels low-->glucagon is released-->leads to the degradation of glycogen--> and gluconeogenesis--.synthesize glucose from small molecules
  44. Glucagon receptors
    on liver and recetpros
  45. Insulin
    increases glucose uptake and storage-->decreases cAMP-->dephosphorylates-->increase glycogen synthesis,fatty acid synthesis, decreasse gluconeogenesis
  46. Glucagon
    increase in cAMP-->activates PKA-->phosphorylates-->increase glood glucose, gluconeogenesis
  47. Glycolysis
    occurs in the cytoplasm
  48. Glycolysis in RBC and brain
    sole source of ATP for RBC, total glucose oxidation supplies almost all the ATP for brain (fatty acids can't cross BBB)
  49. Glycolysis in Skeletal muscle
    supplies almost all the ATP under aerobic conditions
  50. Glycolysis in Liver
    function depends on nutritional and hormonal state (well fed vs. fasting state)
  51. GLUT transporters
    GLUT1 in Brain and RBC, GLUT2 in intesinal epithelial, liver, GLUT4 in muscle and adipose tissue
  52. Glucokinase
    first step in converting glucose-->gluc 6-P, high Km, low affinity for glucose, never saturated, can always take up glucose
  53. Hexokinase
    first step in converting glucose-->gluc 6-P, low Km, high affinity for glucose, saturated all times
  54. Two steps that make ATP in
    PEP and 1,3-BP have high energy bond that can drive the synthesis of ATP (only other molecule that does this is creatine phosphate)
  55. Overall reaction of glycolysis (Aerobic)
    Glucose+ 2NAD+ + 2ADP + 2Pi--->2 pyruvate + 2 NADH + 2 ATP
  56. Overall reaction of glycolysis (Anaerobic)
    Glucose + 2ADP + 2 Pi --> 2 lactate + 2 ATP
  57. Vitamin cofactor for NADH
  58. Vitamin for FADH/FADH2
  59. Vitamin for DNA and glucose breakdown (PDH)
  60. Vitamine for CoA (coenyme for PDH)
    B5 Pantothenic acid
  61. Create ROS
    Powerful odizing agent: NADPH Oxidase, superoxide dismutase, myeloperoxidase
  62. Types of ROS created
    O2-, H2O2, HOCl
  63. Glucose 6 Phosphate Dehydrogenase (G6PDH) deficiency
    most important enzyme in pentose phosphate pathway, primary regulation step,causes hemolytic anemia due to inability to detoxift oxidizing enzyme (in pentose phosphate)
  64. Lesch-Nyhan Syndrome (LNS)
    deficiency is hypoxanthin-guanine phosphoribosyl transferase (HGPRT)-->overaccumulation of PRPP (substrate for step 2 in purine biosynthesis), X-linked disorder
  65. Glycolysis 4 main enzymes
    Hexokinase, Glucokinase, PFK-1,PK
  66. Gluconeogensis site
  67. Fasting hypoglecemia (gluconeogenesis)
    overnight fasting begin gluconeogenesis
  68. Neonatal hypoglycemia (gluconeogenesis)
    The first 2-3 h after birth, newborn uses gluconeogensis
  69. Alcoholic hypoglycemia (gluconeogenesis)
    first intermediate in gluconeogenesis is oxaloacetate-->translocated to cytosol as malata where NAD+ is needed to regenerate oxaloacetate-->large amt of alcohol reduces NAD+
  70. Glycerol comes into gluconeogenesis at what step
    enters at DHAP
  71. Lactate comes into gluconeogenesis at what step
    enters at pyruvate
  72. Pyruvate carboxylase (PC)
    in mitochondira, turns Pyruvate-->oxaloacetate, needs ATP + Biotin as CO2 carrier
  73. 3 major carbon sources for gluconeogenesis
    glucogenic AAs, Lactate, Glycerol
  74. Glucogenic amino acids
    from degradation of skeletal muscle protein--only 2 of 20 cant be used for glucose synthesis--can enter back in as pyruvate or other places in TCA cycle
  75. AAs that can't be used for glucose synthesis
    leucine and lysine
  76. Lactate in gluconeogenesis
    from anaaerobic muscle of RBC-->LDH convers lactate to pyruvate-->goes into gluconeogenesis
  77. Glycerol in gluconeogenesis
    3C compound from adipose tissue to liver-->to be converted back to glycerl-3P-->oxidation to DHAP-->goes into gluconeogenesis
  78. Kori Cycle
    Lactate cycle to take lactate back to the liver to convert them back to glucose--uses enzyme LDH
  79. Alanine cycle
    Takes alanine back to the liver to convert it back to glucose--uses enzyme alanine transaminase
  80. Glycogen
    the energy storage polysaccharide in animals
  81. Tissue synthesis and storage
    liver and skeletal muscle
  82. Glycogen torage capacity is limited by
  83. Insulin stimulates
    glycogen synthesis
  84. Glucagon and epinephrine stimulate
    glycogen breakdown (epinephrine triggers cAMP, epnephrine is important in muscle)
  85. Skeletal muscle only have _________ receptor for signaling glycogen breakdown
    epinephrine (muscle doesn't have glucagon receptors)
  86. # of glucose residues in glycogen granule in muscle
    60,000 (in liver there are more)
  87. Glycogen granule structure
    polysaccharide core alpha 1,4 and alpha1,6 bonds, protein coat has all the enzymes to synthesize, degrade and regulate glycogen
  88. Glyogenin
    the core protein at the center of glycogen core, only reducind end, everything else is non reducing
  89. Branching in glycogen
    significant for break down, the more branch points you have the more effeicient in taking up glucose in hyper glycemia
  90. Enzyme that mucles lacks for the release of glucose
  91. Muscle glycogen
    oxidizes glucose via glycolusis to cupply muscle with ATP for contraction-->does not release it into the bloodstream
  92. Liver glycogen
    supplies blood with glucose between meals
  93. Glucose receptor in muscle
  94. Liver receptor in liver
  95. Phosphoglucomutase
    Enzyme that converts Glucose-6 phosphate (G6P)-->Glucose-1 phosphate (G1P)
  96. Gout
    condition caused by monosodium urate monohydrate (MSU) crystals in and around the tissues of joints,
  97. Hyperuricemia
    elevated serum urate above 6.8 mg/DL
  98. Variations in serum urate levels
    age (serum urate increases with age, gender (women get symptoms after menopause, men 10 yrs after puberty), diet (high in purines)
  99. 3 clinical stages gout
    stage 1; acute gouty arthritis, stage 2: intermittant gout, stage 3: chronic gouty arthritis
  100. Definitive Diagnosis
    identification of MSU crystals in synovial fluid leukocytes
  101. Lesch Nyan syndrome
    deficiency in HPRT-->leads to increase in PRPP, guanine and adenine-->increase urate levels, only incident of prepubescent gout
  102. Allopurinol
    treatment for gout that blocks the activity of xanthine oxidase-->stops the conversion of purines to urate
  103. Best way to diagnose gout
    take a sample of tophus fluid
  104. Testing synovial fluid for gout
    order cell count, gram stain, crystal analysis
  105. Pentose phosphate pathway
    occurs in the cytosol,, branches from glycolysis, generates pentose phosphates for synthesis of RNA and DNA, important for RBCs, generates NADPH (anabolic)
  106. NADPH in pentose phosphate
    generated from pentose phosphate pathway found in liver, adrenal cortex, RBC, involved in the biosynthesis of fatty acid, cholesterol, steroid hormones, bile salts
  107. Hepatocyte cytoplasm ratio of NADPH/NADP+ and NADH/NAD+
    NADPH/NADP+= 10/1 NADH/NAD+=1/1000
  108. Primary role of NADPH
    reduction of glutathione (GSH), maintenance of reduced glutathione, fatty acid and steroid synthesis
  109. Glutathione
    AN ANTIOXIDANT (made of: SH+ glycine + cysteine + glutamate) maintain membrane integrity in its reduced state
  110. RBC energy derivation
    gets energy by converting glucose into two molecules of lactate-->gains 2 ATP
  111. How much of the glucose entering RBC is used for pentose phosphate pathway?
  112. Are oxidative reaction reversible?
    No, they are irreversible
  113. Are nonoxidative reaction reversible?
  114. Redox stage Pentose phosphate pathway
    1. G6P (NADP+-->NADPH + Glucose-6 phosphate dehydrogenase) -->6-phosphogluconolactone, 2. 6-phosphogluconolactone (lactonase) --> 6-phosphoglucanate, 3. 6-phosphoglucanate is oxidatively decarboxylated (6-phosphogluconate dehydrogenase, NADP+-->NADPH)-->ribulose-5-phosphate
  115. Step 2 of pentose phosphate pathway
    6-phophogluconolate (lactonase, NADP+-->NADPH)-->6-phosphoglucanate dehydrogenase, Irreversible and not rate limiting
  116. Glucose-6 phosphate dehydrogenase (G6PD) deficiency
    Causes hemolytic anemia due to inability to detoxify agents (owing to insufficient amt of reduced glutathione)
  117. Variable level of G6PD deficiency
    class 1 (very severe, 2%) --> class IV (none, 60-150%)
  118. Interconversion of pentose phosphate pathway
    To create NADPH: transketolase and transaldolase convert carbon skeletons of 3 molecules of ribulose-5-phosphate -->form 2 molecules of Fru-6-P and one Glyceraldehyde-3-P
  119. Interconversion of pentose phosphate pathway
    To create riboseL nonoxidative reactions can synthesize ribose-5-P from Glyceraldehyde-3-P
  120. Transketolase
    Thiamine diphosphate (TPP) is cofactor for transketolase, need thiamine for pentose 5- phosphate production
  121. TPP
    cofactor for transketolase, pyruvate carboxylase, alpha-ketoglutarate dehydrogenase (TCA cycle), brnached alpha keto acid dehydrogenase
  122. If you are deficient in thiamine
    reduce TPP-->reduce the amount of NADPH synthesis via pentose-5 phosphate pathway
  123. Where does cholesterol biosynthesis occur?
    cytoplasm of hepatic cells (liver)
  124. What is the rate limiting enzyme in cholesterol biosynthesis?
    HMG CoA reductase
  125. Action of phospholipases
    Cleave phospholipids-->make Arachadonic Acid
  126. Eicasanoids
    synthesized in membrane-->made from AA-->signal via G-proteins made via COX 1 and COX 2
  127. Leukotrienes
    made from arachadonic acid via lipoxygenases
  128. HETE
    made from AA via cytochrome P450--> 20-HETE implicated in hypertension-->inhibited by NO/CO
  129. COX 1
    cyclooxygenase 1, constituitive found in platelets, kidney and stomach
  130. COX2
    inducible, responsible for imflammatory prostaglandin synthesis
  131. Nonselective COX inhibitors
    NSAIDS-aspirin, tylenol-->irreversibly inactivates COX 1 and 2 by blocking PGG2-->block production of thromboxane (vasoconstrictor) and clot builder
  132. Selective COX 2 inhibitors
    celecoxib and rofecoxib
  133. Steroidal anti-inflammatory drugs
    Prednisone-->inhibits PLA2 from converting DAG to arachadonic acid
  134. 5-lipoxygenase (5-LO)
    used to convert AA to 5HPETE
  135. FLAP
    used to convert AA to 5HPETE
  136. Activation of leukotrienes
    Activated leukocytes-->send signals for PLA2 to cleave membrane phospholipids-->AA is liberates-->5-LO and FLAP convert AA-->5-HPETE--->LTA4---> converted by LTA4 hydrolase to LTB4
  137. mineralocorticoids
    involved in mineral balance, retention of sodium, excretion of potassium, regulating blood pressure
  138. aldosterone
    mineralocorticoid, stimulates sodium reabsorption and causes increase in blood pressure
  139. glucocorticoids
    steroid hormones important for anti-inflammatory and stress responses, immunosuppresive
  140. cortisol
    key glucocorticoid, regulates cardiovascular and metabolic function, including stimulation of gluconeogenesis
  141. pathway of cortisol synthesis
    cAMP-->PKA-->phsophorylates 20-22 desmolase-->forms cortisol
  142. hormone responsible for cortisol release
  143. hormone responsible for aldosterone release
    Angiotensin II
  144. cyt450P
    mixed function oxygenases, converts arachidonic acid-->20 HETE via oxidation
  145. pathway of aldosterone synthesis
    angiotensin II--> DAG + IP3 (IP3 --> Ca2+)-->PKC-->phosphorylates 20-22 Desmolase-->forms aldosterone
  146. rate liminiting enzyme for synthesis of steroid hormones
    20-22 desmolase, cleaves off all but 2 Cs of the side chain on the D ring of cholesterol, regulated by phosphorylation/dephosphorylation via the secondary messenger cAMP-->PKA
  147. what hormone is deficient in the case of the virilized baby girl
    21-hydroxylase-->leads tot increased testosterone production--?decreased production of cortisol and aldosterone
  148. pathway of virilized baby girl
    cells of adrenal cortex-->produce angionentsin II--> activates the production of aldosterone
  149. congenital adrenal hyperplasia
    pituitary __>releases ACTH-->(regulated by corticaol feeding back and inhibiting productiond of ACTH)
  150. cause of salt wasting in the case of the virilized baby girl
    decreased aldosterone production-->NA+ loss-->hyponatremic dehydration
  151. cause of hypoglycemia in virilized baby girl
    21 hydroxylase deficiency causes lack of cortisol-->no gluconeogenesis-->drop in blood glucose-->hypoglycemia
  152. citic acid cycle
    citrate-->isocitrate-->alpha-ketoglutarate-->Succinyl CoA-->Succinate-->Fumarate-->Malate (shuttle)-->Oxalacetate
  153. Products of citric acid cycle
    NADH and FADH2-->for aerobic production of ATP
  154. Electon transport chain
    generates bulk of ATP for maintaining homeostasis through oxidative phosphorylation
  155. Where does ETC occur?
    Inner mitochondrial membrane
  156. ETC complexes
    Complex I-IV on inner mitochodrial membrane + 2 electron shuttles (CoQ and Cyt C) + Complex V generates ATP but has no enzyme activity
  157. Complex I
    NADH Q reductase-->transfer 2 electrons from NADH and proteins to CoQ
  158. Complex II
    succinate DH + Glycerol phosphate DH + Fatty actl CoA DH (+ CoQ electron shuttle)-->2 electronsof FADHs passes on to CoQ along with 2 protons
  159. Conezyme Q (CoQ)
    CoQ is small lipid soluble, diffues and shuttle electrons though membrane to compleX III
  160. Complex III
    cytochrom bc 1 complex-->transfers electons to Cyto C
  161. Cytochrome C
    Water soluble protein-->accepts electons from II and shuttles them to complex IV
  162. Complex IV
    cytochrome oxidase-->uses Fe and Cu-->transfers electrons to O2-->1 molecule H2O produced for each molecules of NADH of FADHs oxidized-->4 electrons transferred=4H+-->O2-->2 H2O
  163. Reducing agent at step 1 electron transport chain
  164. Gout (cause)
    monosodium urate monohydrate (MSU) crystals in and around the tissues of joints
  165. Gout characteristics
    elevated serum urate (hyperuricemia >6.8 mg/dL), recurrent acute arthritic attacks, presence of MSU crystals inside synovial leukocytes, MSU aggregates deposited in and around joint, renal disease
  166. Hyperuricemia
    >6.8 mg/dL, anyone with hyperuricemia is arisk for gout
  167. Variations in serum urate levels
    age (older you get the higher they are), gender (women don't get symptoms until after menopause), diet (high in purines like meat, shrimp, animal products)
  168. 3 clinical stages of Gout
    preceded by asymptomatic hyperuricemia, Stage 1: Acute gouty arthritis, Stage 2: intermittant gout, Stage 3: chronic gouty arthritis
  169. Definitive Diagnosis
    identification of MSU crystals in synovial fluid leukocytes, identification of MSU crystals from tophus
  170. Purine synthesis
    purines made de novo from Ribose 5-P + ATP---(PRPP synthetase)-->PRPP-->IMP--->Inosine-->Hypoxanthine-->Xanthine---(xanthine oxidase)->Urate
  171. Adenine enters the PRPP pathway by which enzyme
    Adenine phosphoribosyltransferase (APRT)
  172. Guanine and Hypoxanthine enter PRPP pathwya by which enzyme
    Hypoxanthine-Guanine phosphoribosyltransferase (HGPRT)
  173. HPRT Salvage pathway
    let you reuptake purines and recycle them
  174. Lesch Nyhan Symdrome
    X-linked disorder (pre-pubertal boys) HPRT deficiency--> increase in PRPP, guanine, adenine, urate
  175. Allopurinol
    treatment for gout, blocks at xanthine oxidase
  176. Why do gout attacks occur at night?
    pKa (level at reactants=products) of uric acid is 6, at night when we are sleeping-->respiratory acidossi-->shifts products to less soluble side
  177. Synovial fluid analysis (for gout diagnosis)
    gross appearance, order cell count and differential (look for neutrophils, microbiology culture, gram stain, crystal analysis if gout is suspected-->need resh specimen because solutes can dissolve
  178. Crystal analysis in gout
    polarizing microscope with compensator (MSU found in 90% of acute attacks, lower percent chronically)--can differentiate from pseudogout
  179. Synovial fluid analysis in gout
    normal=clear, slightly viscous, WBCs low, no RBCs, no crystals, negative culture, gout fluid=tubid, opqaue, lots of WBCs, negative gram and culture, MSU cyrstals, negative birefringence
  180. Medical problems with increased risk for gout
    hypertension, obesity, high alcohol intake, high meat intake, hyperinsulinemia, metabolic syndrome
  181. Purine catabolized to one common free base ______
  182. Final step in Purine metabolism
    xanthine oxidized by xanthine oxidase to form uric acid
  183. Fatty acid oxidation (energy provision)
    provides half the oxidative energy required for liver, kidney, heart and skeletal muscle
  184. Lipid metabolism (outline of steps)
    Lipid mobilization (TAGs hydrolyzed in adipose tissue to fatty acids plus glycerol)-->transport FAs in blood to the tissues-->activation of fatty acids as CoA ester-->transport to mitochondria via carnitine shuttle-->metabolized to acetyl CoA
  185. Triacylglycerol (TAG)-->free fatty acids (FFA)
    TAGs---(via DAG)---> glycerol + FFAs
  186. Chylomicrons
    transport fats
  187. Lipoprotein
    transfer TAGs made in liver
  188. Carnitine shuttle
    needed for the transportation of long chain fatty (12-20) acidsfrom cytosol into mito matrix
  189. Methylmalonic acidemia
    missing the methylmalonyl CoA mutase to convrt odd chain fatty acids to succinyl CoA-->huge build up of methylmalonyl CoA-->metabolic acidosis and developmental retardation
  190. Methylmalonic aciduria
    unable to convert B12 to coenzyme form-->flood urine with methylmalonic acid-->huge build up of methylmalonyl CoA-->metabolic acidosis and developmental retardation
  191. Degradation of odd chain fatty acids
    propionyl CoA---(biotin as Co2 carrier)-->methylmalonyl CoA---(B12 coenzyme form + methylmalonyl mutase)-->succinyl CoA--->citric acid cycle
  192. Degradation of even chain fatty acids
  193. Phytanic acid & branched chain
    alpha-oxidation of phytanic acid (releases CO2)-->now thiokinase can anneal CoA-->proceed to B-oxidation to make acetyl CoA OR propionyl CoA-->succinyl CoA
  194. Jamaican vomiting sickness
    ackee plant contains hypoglycin-->inhibits medium and short chain dehydrogenases-->inhibits B-oxidations
  195. Carnitine deficiency
    no carnitine=no carnitine shuttle=you can't do b-oxidation of long chain FAs-->nonketotic hypoglycemia because you can't produces muscle aches and weakness following exercise
  196. Zellweger Syndrome
    absence of peroxisomes in liver and kidneys-->can't degrade very long chain FAs-->accumulation of long chain FAs in the brain
  197. PKU
    defect in the enzyme phenylalanine hydroxylase which converts phenylalanine--> tyrosine ( unable to break down phenylalanine)-->build up toxic metabolites 2-hydroxyphenylacetic acid, phenylpyruvid acid, pneyllactic acid
  198. hypomorphic mutation of enzyme defiency
    some activity, but loss of function
  199. null mutation of enzyme defiency
    no enzyme
  200. Biotinidase deficiency
    deficient in the enzyme that converts biocytin to biotin-->results in problem in the catabolism of branch chain amino acid
  201. Other enzyme realted deficiencies
    disfunctional protein (hypomorphi or null), deficient cofactor (vitamin), deficient activator protein, deficient transcription factor
  202. Metabolis Basis of disease
    deficiency of product-->substrate for th next reaction-->energy (ATP) OR toxic metabolites
  203. testing for enzyme deficiency in blood
    serum amino acids, serum ammonia, acylcarnitine (tandem mass spec)
  204. testing for enzyme deficiency in urine
    urinary amino acids (UAA metabolites in TCA cycles), urinary organic acids, urinary acylcarnitine (tandem mass spec), GAGs
  205. errors in mitochondrial fatty acid oxidation
    autosomal recessive inherited, potentially fatal disorders, intolerant of exercise
  206. disease characteristics
    severe hypoglycemia/poor ketogenesis, sudden infant death, intolerance-muscle disease, heart disease (especiallyin long chain fatty acids), fatty liver
  207. MCAD deficiency
    most common (1/60-->1/100 people are carriers), autosomal recessive, point mutation in exon 11, high concentration of Mchain FAs, acyl carnitines, acyl glycines in plasma and urine
  208. Trifunctional protien
    2 subunits (alpha and beta)
  209. Trifunctional protein alpha subunit (HADHA)
    involved LCHAD
  210. Trifunctional protein beta subunit (HADHB)
    ketoacyl CoA thiolase
  211. LCHAD deficiency in fetus
    toxic baby syndrome can cause the build of of LCHAD in fetal circulation, late in pregnancy mother will develop HELLP syndrome
  212. HELLP syndrome
    hemolysis, elevated liver enzymes, low platelets seen in pregnant mothers, caused by an LCHAD deficiency in the fetus
  213. gas chromatography-mass spectrometry
    used to detect urinary organic acids in mitochondrial fatty acid oxidation disorders
  214. How to treat VLCAD deficiency?
    give MCADs, bypass the block OR give triheptanoin (C7) triglyceride-->KBs can be produced from odd chain FAs