HB1- exam 2 note cards grabbag.txt

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HB1- exam 2 note cards grabbag.txt
2010-10-06 18:26:21
toxic baby you checkered shirt go get AED

you in the checkered shirt, go get the AED!
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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
  215. Where are primary bile salts created?
    cytoplasm of liver parenchymal cells
  216. Bile salts are used to...
    emulsify fats (soap molecules, hydrophobic on one side hydrophilic on the other)
  217. At physiological pH bile salts are
    mainly ionized
  218. Rate rate limiting enzyme for bile salt production
    7-alpha-hydroxylase enzyme (CYP7A1)
  219. CYP7A1
    rate limiting enzyme in bile acid production, installs the OH group at position 7
  220. Where are secondary bile salts created?
    by bacterial enzyme cleave og primary bile salts in intestines
  221. What controls bile secretions?
  222. How do bile salts get back to liver?
    portal vein
  223. How much bile acids pass through the bile duct each day?
  224. How much of total bile is excreted in feces?
  225. Where do statins inhibit?
    HMG CoA reductase
  226. What makes gallstones?
    bile supersaturated with cholesterol
  227. steroid hormones
    made from cholesterol
  228. Corticosteroids
    C21 steroid hormones (Ex.progesterone) made in the adrenal cortex
  229. Androgen
    C19 steroid hormones (Ex.androgens) made in the testis
  230. Estrogens
    C18 steroid hormones (Ex.estrogen) made in the ovary
  231. Steroid hormone excretion
    preprocessed to be more water soluble then excreted via the kidney --> in urine
  232. Mechanism of action of steroid hormones
    act via nuclear action
  233. Type I steroid hormones
    act via cytoplasmic receptors to form steroid-receptor complex--->receptor dimerizes-->nuclear localization signal exposed-->complex enter nucleus and binds to SRE (specific response element)-->functions as transcription factor-->enhance/repress gene expression
  234. How do steroid-receptor complexes find DNA sequence?
    Zinc Finger on the receptor feels the DNA to find the palandromic
  235. Why are glucocorticoid receptor zinc fingers differ from standard zinc finger?
    it has four cysteine instead od 2 cysteines and 2 histidines
  236. insulin
    synthesized in pancreatic beta cells, anabolic hormone-->acts to decrease glucose in the blood
  237. glucagon
    synthesized in pancreatic alpha cells, catabolic hormone-->action to increase blood glucose
  238. Insulin synthesis
    preproinsulin-->signal peptide cleaved=proinsulin---->C-peptide cleaved= insulin
  239. 2 phases of insulin release
    phase 1, five steps (glucose comes into B-cells-->glucose is phosphorylated-->glycolysis-->increase in ATP-->close ATP gated K channel-->depolarization-->open voltage gated Ca channels-->trigger insulin release
  240. Why is insulin response to oral glucose high than IV infusion
    because GI hormones help to increase insulin secretion
  241. Insulin binding to membrane receptor in muscle/adipose
    dimerizes tyr-kinase receptor-->autophosphorylates-->phosohporylates IRS1-->activated a lot of pathways-->recruits GLUT4 to membrane
  242. What enzyme does muscle lack?
    Glucose-6-phosphatase-->can't release glucose in the bloodstream
  243. Is GLUT 2 insulin dependent/independent?
    independent, it is always one regardless of insulin level
  244. Is GLUT 4 insulin dependent/independent?
    dependent, glucose transport in muscle and adipose tissue depends on insulin levels
  245. What kinds of metabolism does insulin affect?
    carbohydrate, lipid, protein, ALSO PROMOTES POTASSIUM UPTAKE
  246. Does GLUT4 mostly reside intracellularly or on the plasma membrane?
    intracellularly, 90% is inisde the cell waiting to be mobilized to plasma membrane
  247. How much does insulin affect GLUT4 receptor recruitment to surface?
    insulin doubles recruitment of GLUT-4 receptors to plasma membrane
  248. In type II diabetes, what is the most important cause of insulin resistance?
    Defective insulin signaling (also, decreased # and affinity of receptors)
  249. How do Type II diabetes patients first present?
    impaired glucose tolerance
  250. What causes insulin resistance?
    post-receptor signal transduction defects (defective tyr-kin, mutations in genes coding for IRS1, defective translocation of GLUT2 to cell membrane)
  251. Glucagon
    mobilizes glucsoe from every available fuel source, increases lipolysis and ketogenesis from acetyl CoA
  252. Glucagon mode of action
    binds to its own receptor via G-protein couple proteins-->activates Adenyl Cyclase-->activates cAMP cascade--> activates PKA-->phophorylates PFK2-F2,6BPase-->activates F2,6BPase-->stimulate gluconeogenesis
  253. Does muscle has glucagon receptors?
  254. How do you stimulate gluconeogensis in muscle?
    Epinephrine stimulates glycogenolysis and gluconeogenesis (and inhibits glycolysis and lipogenesis)
  255. What receptors does epinephrine bind to?
    alpha and beta adrenergic
  256. What is the key enzyme responsible for hyperglycemia with stress?
  257. Foxo1 and Foxa2
    fork-head winged-helices, transcription factors that promote gluconeogenesis, synthesis is regulaated by insulin
  258. Foxo1
    promotes gluconeogensis in the liver in the fasting states by inducing the PEPCK and G-6-Pase enzymes (insulin phosphorylates foxo1 to blocks gluconeogenesis)
  259. Foxa2
    regulates fatty acid oxidation in fasted state by induing genes encoding for enzymes of glycolysis, FA oxidation and ketogenesis (insulin phosphorylates foxa2 to inhibits FA oxidation)
  260. Diabetes lab values
    >126 mg/dL fasting glucose or >200mg/dL after glucose tolerance test
  261. Normal lab values for blood glucose
    <110 mg/dL
  262. Impaired fasting glucose
  263. Cori cycle
    allows recycling of lactate (from muscle anaerobic glycolysis) back to glucose (in liver) via gluconeogenesis
  264. Glucose-alanine cycle
    allows recycling of alanine (from muscle proteolysis) back to glucose (in liver) via gluconeogenesis
  265. Metabolism during stress
    hypermetabolic state
  266. Sympathetic nervous system drives response of stress via what hormones?
    epinephrine, glucagon, cortisol-->stimulates catabolism (glycogenolysis, lipolysis, proteolysis)
  267. Can stress induce insulin resistance?
    yes-->glucocorticoid hormone (GLUCAGON) stimulate gluconeogenesis by encoding genes for G6Pase and PEPCK
  268. Two main components of Diabetes
    hyperglycemia and vascular complications
  269. Vascular effects of diabetes
    oxidative damage of the small (microangiopathy) and large (macroangiopathy) arteries via ROS and AGE products
  270. Organs affected by microangiopathy
    kidney (diabetic nephropathy) and retina (diabetic retinopathy)
  271. Cause of cataracts in diabetics
    caused by glycated proteins through sorbitol oxidation
  272. Type II diabetes
    insulin independent, insulin resistant caused by B-cell failure
  273. Type I diabetes
    caused by autoimmune attack of pancreatic B-cells (insulin-dependent)--> leads to fasting hyperglycemia
  274. Symptoms of Type I diabetes
    polyuria, polydypsia, ketonemia (increased blood ketone bodies), ketonuria, overproduction of acetoacetic acids, metabolic acidosis
  275. Genetic component of Type I Diabetes
    HLA genes on chromosome 6, siblings have 10% increased risk of Type I diabetes if their siblings are affected
  276. Main complication of Type II Diabetes
    macrovascular components-->leads to coronary artery disease
  277. Amadori products
    glycated hemoglobin, most highly studied (AGE) glycated proteins
  278. AGEs
    Advanced glycated endproducts-->bind to membrane receptor-->make ROS-->recruit inflammatory proteins and cytokines
  279. Polyol pathway
  280. Diabetic neuropathy
    caused by sorbitol build up in the brain/nerve tissue
  281. How does insulin affect K
    insulin increases cellular uptake
  282. K levels in Diabetes
    lack of insulin= K efflux from cells-->osmotic diuresis-->
  283. Fat soluble vitamins
    A,D,E,K-->stored in tissues (not as readily extracted from diet as watr soluble vitamins)
  284. Vitamin A
    stored in liver, 3 compounds: retinol, retinoic acid, retinal-->retinoic acid most active, visual pigment rhodopsin found in the rod cells of the retina
  285. Pro-vitmain precursor to vitamin A
    Beta carotene
  286. Vitamin A deficiency
    common most cause of blindness in the world (defective night vision-->prgressive keratinization and blindness)
  287. Vitamin A excess
    leads to bone loss, hair loss, hepatosplenomegaly. nausea, vomiting
  288. Vitamin D
    is really a hormone, usually only vitamin required in diet, produced by the action of UV light on provitamins (7 dehyydroxycholesterol)
  289. Causes of Vitamin D deficiency
    insufficient sunlight, increased vitamin D metabolism due to low calcium intake
  290. Deficiency in Vitamin D results in...
    Vitmain D deficieny Rickets as a result of deficiency of calcium mineral (low circulating calcium concentrations
  291. Vitamin D excess
    causes enhanced calcium absorption and bone reabsorption-->leads to hypercalcemia and calcium deposition-->develop kidney stones
  292. Vitamin E
    mixture of several compounds alled tocopherol and present in 90% of human tissue, richest sources are vegetable oils and nuts
  293. Most abundant antioxidant
    Vitamin E, prevents free radical damage by donating hydrogen to free radical
  294. Vitamin E deficiency
    neurological symptoms, hemolytic anemia, thrombocytosis
  295. Vitamin K
    necessary for blood coagulation, absorption of vitamin K depends on appropriate fat absorption ( like vitamin E), dietary sources green leafy vegetavle, dairy, veg oils
  296. Vitamin K production
    by intestinal microflora-->ensure dietary deficiency does not occur
  297. Vitamin K deficiency
    can occur rarely in newborns with bleeding disorders (given a shot of Vitamin K at birth because the gut of a newborn is sterile)
  298. Vitamin K inhibitors
    antithrombin drugs
  299. Water soluble vitamins
    with the exception of vitamin B12, the body has no storage capacity for water soluble vitamins, No toxicity associated with excess, any excess is excreted in urin
  300. Vitamin B complex
    Act as coenzyme, Not toxicity associated with excess
  301. Thiamine (vitamin B1)
    essential for carboxylation reaction and carbohydrate metabolism, deficiency associated with alcoholism and Beri-Beri disease
  302. Thiamine deficiency
    alcoholism and Beri Beri disease, early sign are loss of appetite, constipation and nausea
  303. Wernicke Korsakoff psychosis
    thiamine deficiency resulting in ataxia, neuropathy, loss of eye coordination
  304. Riboflavin (vitamin B2)
    associated iwth oxidoreductase, attached to sugar alcohol ribitol, found in oxidoreductases as FMN and FAD, required for energy metabolism
  305. Riboflavn deficiency
    causes inflammation of the mouth and tongue, scaly dermatitis-->Pellagra
  306. How do you measure Riboflavin status
    erythtrocyte glutathione reductase activity
  307. Niacin (Vitamin B3)
    required for NAD+ and NADP+ synthesis-->oxidoreductase reactions, synthesized from tryptophan in liver
  308. Pyridoxine (Vitamin B6)
    important in amino acid metabolism and participates as cofactor for amino acid metabolism especially transamination and decarboxylase
  309. Pyroxidine deficiency
    causes irritability, nervousness, depression-->leads to neuropathy, convulsions and coma
  310. Biotin
    Important in carboxylation reaction, lipogenesis, gluconeogenesis, catabolism of branched chain AAs, normally synthesized by intestinal flora
  311. What can cause Biotin deficiency?
    consumption of raw eggs can cause biotin deficiency because egg white protein, avidin, combine with biotin preventing its absorption
  312. Panthotenic Acid (Vitamin B5)
    part of CoA
  313. Folic acid
    important in single carbon transfer reactions such as methylation reactions in metabolism and gene expression
  314. Folic acid deficiency
    leads to hyperhomocysteinemia-->increased risk of cardiovascular disease
  315. What vitamin plays a role in the synthesis of purine and pyrimidines
    folic acid
  316. Deficiency of what vitamin leads to megaloblastic anemia?
    folic acid-->enlarged blast cells in bone marrow
  317. Most common cause of folate deficiency
    pregnancy--due to increased demand
  318. Cobalmin (Vitamin B12)
    Similar structure to heme, excpet Iron replaced by cobalt, participates in recycling of folates, found only in food of animal origin
  319. tetrahydrofolate trap
    megaloblastic anemia characteristic of B12 deficiency-->due to reduced folate and accumulation of methyl THF
  320. Vegans are at risk for developing____deficiency
    vitamin B12
  321. Vitamin C
    active form is ascorbic acid-->oxidised to generate vitamin E-->essential nutrient in humans-->fragile and easily destroyed, found in citrus fruits
  322. What vitamin is involved in collagen synthesis?
    Vitamin C
  323. Vitmain C deficiency
    causes scruvy-->hemorrhages, muscle weakness, soft/swollen/bleeding gums, poor wound healing
  324. What vitamin deficiency compromises immune function
    Vitamin C
  325. How do vitamin B6, B12 and folic acid prevent cardiovascular disease?
    by lowering homocystein concentration
  326. Trace elements
    metal ions required as active components in proteins
  327. Zinc
    affects growth, skin integrity, wound healing
  328. Zinc deficiency
    causes skin lesions, sexual impairment, loss of hair (in patients with burns, and renall damage)
  329. Copper
    copper scavenges oxidase and other ROS, associated with cytochrome oxidase and superoxidedismutase, also important in crosslinking collagen
  330. Only was to excrete copper?
    through bile--chronic excessive copper intake results in liver cirrhosis
  331. What is required to incorporate iron into Hb?
  332. Selenium
    forms part of antioxidant enzyme glutathione reductase peroxidase
  333. Selenium defciency
    found in mushroom-->leads to hemolytic anemia
  334. Acidic drugs
    bound to albumin, small Vd (mostly in plasma), often hydrophilic, often renally excreted, less extensively metabolized
  335. basic drugs
    Bound to alpha1-acid glycoprotein, often lipophilic (distrubted more in tissue), usually metabolized (first pass)
  336. Lipoprotein lipase disorder (Ia)
    LPL gene defect, Autosomal recessive, increase in chylomicrons, find erruptive xanthoma, hepatoslpenomegaly, pancreatitis
  337. Familial dysbetalipoproteinemia (III)
    apoE gene defect, Autosomal dominant or recessive, increase in chylomicrons and VLDL remnants, symptoms: xanthomas, CHD, PVD
  338. Familial hypercholesteromia (IIa)
    defect in LDL receptor, autosomal dominant, increased LDL, symptoms include tendon xanthomas and CHD
  339. Familial defective apoB-100 (IIb)
    defect in apoB-100, autosomal dominant, increased LDL, symptoms include tendon xanthomas and CHD
  340. Inherited disorders of Low HDL are _____
  341. Apo-A1 deficiency would result in _______ HDL levels
  342. Tangier Disease
    ABCA1 deficiency-->results in low levels of HDL
  343. Hypothyroidism causes an _______ in LDL
  344. What can increase HDL?
    alcohol,exercise, estrogen
  345. What can decrease HDL?
    obesity, smoking, type II diabetes, malnutrition, anabolic steroid, beta blockers
  346. What can increase Triglycerides?
    autoimmune disease, type II diabetes
  347. What can increase Lp (a)?
    renal insufficiency, hypothyroidism, menopause, nephrosis
  348. Atorvastatin (Lipitor)
    statin, decrease LDL levels, increased HDL, decreases triglycerides
  349. Gemfibrozil
    Fibrate, for hypertriglyceridemia, functions as PPAR-alpha agonist, stimulate beta oxidation of FAs, stimulate lipoprotein lipase activity
  350. Niacin
    inhibits lipolysis by blocking hormonsensitive lipase, stops FFAs from being mobilized from adipocytes, inhibits triglyceride synthesis-->decrease synthesis of LDLs, INCREASE HDL, decrease Lp(a)
  351. Niacin vs. Fibrates
    both treat hypertriglycerimedia, use Niacin is patient is on Warfarin
  352. Niacin pharmacokinetics
    undergoes first pass metabolism, converted to NAD and other metabolites because excreted in urine
  353. Niacin adverse effects
    cutaneous flushing due to prostaglandin release-->corrected with administration of aspirin
  354. omega 3 fatty acids for lipidemias
    increase beta-oxidation , increase lipoproteinlipase activity, adjunct therapy in combo with other drugs
  355. Cholestyramine
    Bile acid binding resin, anion exchange resins that bind up bile acids and bile salts in small intestine
  356. Bile acid binding resins
    decrease LDL, can combine with statin, prevent reabsorption and enterohepatic recirculation of bile,indirect way of depleting the body of cholesterol
  357. Drug interaction: bile acid binding resins
    interfere with the absorption of anionic drugs, and fat soluble vitamins (ADEK)
  358. Ezetimibe
    inhibits the absorption of cholesterol at the brush border of the small intestine (adjunct) only effects exogenous cholesterol taken in by food (30-40%)
  359. Pharmacokinetics Ezetimibe
    oral, very water soluble, intestinal glucuronidation facilitates absorption (usually glucuronidation decreases absorption)
  360. Noncompetitive inhibitors
    grapefruit juice (DHB) and nifedipine
  361. Which is the most frequently involved in drug metabolomics?
    CYP 3A4
  362. What else is HMG CoA used to make (besides cholesterol)?
    ketone bodies
  363. What enzyme is used on HMG CoA in KB synthesis?
    HMG CoA lyase
  364. How do you go back to HMG CoA in the cholesterol biosynthesis?
    Transmethylglutaconate shunt (escape hatch)
  365. How many moles of ATP are required to make 1 mol cholesterol??
  366. How many moles of Acetyl CoA are required to make 1 mol cholesterol??
  367. How many moles of NADPH are required to make 1 mole of cholesterol??
  368. Where do you get the NADPH used in cholesterol biosynthesis?
    Pentose phosphate pathway
  369. What converts cholesterol into cholesterol ester (refrigerator)?
  370. What happens as a result of increased cholesterol intake in diet?
    inhibiton of cholesterol biosynthesis and inhibition of LDL receptor
  371. In the presence of sterol SCAP is ___________, transcription of cholesterol biosyntheis is _________, esterification of cholesterol is___________?
    inhibited, downregulated, activated
  372. What is SCAPs role in cholesterol biosynthesis
    brings SREBP to the protease-->activates SREBP--->activates transcription of LDL receptor and HMG CoA reductase
  373. What is an oxysterol
  374. What binds to LXR?
  375. What helps HDL bind peripheral cell?
  376. What does ABCA1 do in cholesterol transport?
    moves cholesterol from the peripheral tissue-->HDL
  377. Steroid hormones vs. polypeptide hormones affect on gene transcription
    Steroid hormones can directly effect gene transcription, whereas polypep can only indirectly affect gene transcription
  378. Polypeptide hormones mechanism of action
    Cannot cross membrane, must bind to cell surface receptors and initiate effects via second messengers (cAMP, Ca2+, etc)
  379. Example of how small molecules can cross membrane
    Nitric oxide
  380. Nitri oxide mechanism of action
    give angina patients glycerol trinitrate-->convert to NO-->NO stimulates guanylate cyclase-->changes intracellular Ca2+-->dilation of blood vessel
  381. Arachidonic acid
    C20 unsaturated fatty acid, lipid 2nd messenger or inflammatory messenger
  382. Eicosanoids
    second messengers synthesized in membrane from AA, signal via G-coupled proteins, made via COX-1 and COX-2 enzymes (prostaglandins, prostacylins, thromboxanes, leukotrienes)
  383. Leukotrienes
    Made from AA via lipoxygenases
  384. phospholipase A2 (PLA2) is a enzyme that cleaves off what?
    a fatty acid
  385. Phospholipase A2 cleaves fatty acids off, which can be converted into ________ and ______________?
    leukotriene and prostaglandins
  386. Prostaglandins
    eicosanoid, fever inducers
  387. Thromboxane
    eicosanoid, vascoconstrictors
  388. Prostacyclins
    eicosanoid, vasodilator
  389. What converts arachidonic acid to PGG2 ( eventually leading to prostaglandins, prostacyclins, thromboxane)?
    COX-1 and COX-2
  390. What converts PGG2-->PGH2?
  391. What converts arachidonic acid to leukotrienes?
  392. What converts arachidonic acid to HETE?
    cytochrome P450
  393. What inhibits the conversion of arachidonic acid to HETE?
  394. What are other functions of eicosanoids?
    Regulate inflammation, regulate blood flow to organs, control ion transport, induce sleep, vasoconstriction, platelet aggregation
  395. Where are eicosanoids snythesized
    from AA in membranes
  396. What drug inhibits the what enzyme in the conversion of phospholipids/DAG-->arachidonic acid?
    Prednisone, enzyme: PLA2
  397. Nonselective COX inhibitors
    aspirin, ibuprofen, acetominophen (inhibit COX-1 constituitive, COX-2 constituitive)-->affects large organ system (renal GI)
  398. Selective COX-2 inhibitors
    celecoxib and rofecoxib, inhibit the inducible COX-2, specifically ontrol pain, fever, inflammation
  399. How does aspirin, inactive COX1 and COX2?
    irreversibly blocks COX1 and COX2 by acetylation, preventing the production of PGG2
  400. COX-1
    cyclooxygenase 1, constiutive, found in platelets, kidneys and stomach
  401. Leukotrienes
    inflammatory and vasoactive mediators, formed from cleaving arachidonic acid by lipoxygenases
  402. 5-lipoygenase (5-LO)
    converts AA-->5-HPETE this makes-->leukotriene A4
  403. FLAP
    regulator of lipoxygenase enzymes, could be a drug targets
  404. What kind of disorders are associated with reduced lipoxygenase activity?
    40% of myeloproliferative disorders (leukemias)
  405. What reactions are leukotrienes associated with?
    asthmatic and allergic reactions
  406. What does LTB4 attract?
    neutrophils (chemoattractant)
  407. What cells are equpped with LTA4 hydrolase?
    neutrophils and monocytes
  408. What do monocytes differentiate into in tissue?
  409. How do omega-6 and omega-3 differ in chemical structure?
    omega-3 has a double bond at the 3 position, omega-6 has no double bond at the 3 position
  410. Which is more saturated (with hydrogens) omega-3 or omega-6?
  411. Omega-3 is more _____________ than omega-6?
  412. What are the endproducts of omega=3 and omega-6 fatty acids?
    prostaglandins and leukotrienes (less inflammatory for omega-3, more inflammatory for omega-6)
  413. Can you convert omega-3 (good) to omega-6 (bad)?
  414. Good sources of omega-3?
    flax seeds, salmon, walnuts, alpha-linolenic acid (ALA)
  415. Typical US diet high in linoleic (omega 6) vs. linolenic (omega 3) (ratio)
  416. Glucocorticoids
    reduce inflammation by upregulating anti-inflammatory proteins, 2 classes (immunologic and metabolic), metabolic increase gluconeogenesis (Ie, cortisol)-->stimulate fat breakdown in adipose tissue to generate FFA
  417. Mineralocorticoids
    regulate water and salt balance (Na+ retention), aldosterone acts on the kidneys to activate reabsorption of sodium and passive reabsorption of water, active secretion of K, major function in blood pressure and blood volume
  418. aldosterone
    mineralocorticoid hormone, aldosterone produced in the adrenal gland and secretion mediated by angiotensin II (also by ACTH) and local potassium levels, that is activated by PKC
  419. rate limiting step in steroid synthesis
    conversion of cholesterol to pregenenolone via 20,22 desmolase-->this is limited by the supply of cholesterol in the inner membrane
  420. main glucocorticoid
  421. main mineralocorticoid
  422. How is 20,22 desmolase activated
    via phosphorylation (cAMP-->PKA-->phosphorylates 20,22-desmolase)
  423. How is 20,22 desmolase activated in cells that make cortisol?
    ACHT->cAMP-->PKA-->phosphorylates 20,22-desmolase
  424. How is 20,22 desmolase activated in cells that make aldosterone?
    angiotensin II-->increase IP3 and DAG-->cAMP-->PKC-->phosphorylates 20,22-desmolase
  425. Describe the role of cyt P-450 mixed function oxygenases?
    in combination with NADPH, FAD, Fe3+, O2 to form hydroxylated product
  426. What enzyme deficiency causes congenital adrenal hyperplasia?
  427. What is the cause of salt wasting in the case of the virilized baby girl?
    The underactivation of renin (converts angiotensinogen-->angiotensin) because of a lack of aldosterone-->results in decreased sodium and water reabsorption by the kidneys
  428. What vitamin is used to make NAD+
  429. Niacin ______ HDL levels
  430. What vitamin in used to make FAD+/FADH
  431. Pyruvate---> Lactate is oxidation or reduction?
    pyruvate is getting reduced (NADH gets oxidized-->NAD+)
  432. Oxidative phosphorylation
    electron transport chain
  433. substrate level phosphorylation
    glycolysis and succinyl CoA-->succinate (releases GTP)
  434. catabolism
    oxidative, exergonic
  435. anabolism
    reductive endergonic
  436. When does the level of ATP in skeletal muscle decrease?
    in extreme exercise conditions
  437. How much ATP does the body under resting conditions
  438. Phosphocreatine
    some energy generated from anaerobic splitting of a phosphate off of phosphocreatine-->maximum energy tield in about 10 seconds
  439. ATPase
    takes ATP-->ADP (releases energy)
  440. Creatine kinase
    regenerates ATP by: PCr + ADP--> Cr + ATP
  441. Higher intensity exercise
    relies mostly on carbs
  442. Lower intensity exercise
    relies more on fat
  443. What is the primary fuel source for an ultra marathon?
    mostly fats-->you have to slow down
  444. What is the primary fuel source in the first 2 minutes of any exercise?
    carbs (anaerobic)
  445. High energy phosphate bonds
    1,3 BPG, PEP, A third is creatine phosphate that has enough energy to synthesize ATP
  446. Total oxidation of glucose gives you
    H2O and CO2
  447. Quickest type of regulation
  448. Rate limiting enzyme in glycolysis
  449. What regulates PFK-1 in muscle?
    AMP (activates), ATP and citrate (inhibits)
  450. What regulates PFK-1 in liver?
  451. What inhibits Hexokinase
  452. Liver isozyme of pyruvate kinase is inhibited by what?
    covalent: phosphorylation by PKA, allosteric: ATP and alanine
  453. AMP Kinase
    allosterically activated by AMP-->know ATP is low-->activates pathways that generate ATP (B-oxidation of fatty acids, glucose transport)-->inhibits those that require ATP (fat synthesis, PCr, Cholesterol synthesis)
  454. Fructose can bypass the regulatory steps in glycosis and enter as ________ and _________
    Glyceraldehyde-3-P and DHAP
  455. How does fructose go to DHAP?
    Fructose-->Fructose-1-P--(F1P aldolase)--> DHAP
  456. hereditary Fructose Intolerance
    F1P aldolase deficiency-->build up in F1P-->decrease in available phosphate-->looks like G1P so acts as competitive inhibitor for glycogenolysis-->HYPOGLYCEMIA
  457. Uridyltransferase deficiency
    accumulate gal-1-P and galactose-->enlarge liver, jaundice, cataract formation, cataracts (build up of galactitol-->product of galactose in the lens)
  458. Nonpermitted transition in conversion between energy sources
    cannot convert FAT to CARBOHYDRATE
  459. Cofactors required for Pyruvate dehydrogenase
    TPP (B1), FAD (B2, riboflavin), NAD (B3, niacin), CoA (B5, panthothenate), lipoic acid
  460. What does PDH release when converting pyruvate-->acetyl CoA?
    NADH and CO2
  461. PDH is a multienzyme complex, how is it regulated?
    PDH kinase and PDH phosphatase
  462. what is oxidative carboxylation?
    blowing off CO2
  463. Where is NAD+ needed in gluconeogenesis
    it is needed in the malatae shuttle to convert malate back to oxaloacetate in the cytosol
  464. 3 types of hypoglycemia
    fasting hypoglycemia, neonatal hypoglycemia, alcoholic hypoglycemia
  465. Pyruvate Carboxylase
    catalyzes first step in gluconeogenesis, converts pyruvate to oxaloacetate, happens in mitochondrial matrix
  466. What is needed for Pyruvate Carboxylase (2 vitamins, 2 other things)
    Biotin, B5, Acetyl CoA, ATP
  467. PEPCK
    converts oxaloacetate to PEP, happens in cytosol, regulation is mostly transcriptional response to glucagon-->CREB-->cAMP, allosteric inhibition by ADP
  468. G-6-Pase
    converts G-6-P to glucose (only in liver, NOT IN MUSCLE), happens in the smooth ER and regulated by transcriptiona (glucagon-->CREB-->cAMP)
  469. McArdle's disease
    deficiency in muscle glycogen phosphorylase-->abnormally high muscle glycogen because you are not breaking it down-->causes weakness, cramping, decreased serum lactate
  470. von Gierke's disease
    Deficiency in Glucose-6-phosphatase (G6Pase)-->glycogen accumulation in liver and kidney-->hypoglycemia, ketosis
  471. Pompe's disease
    Lysosomal alpha-1,4 glucosidase-->glycogen accumulation in lysosomes, early death, normal blood glucose, normal glycogen structure, heart
  472. Cori's disease
    deficiency in debranching enzyme-->abnormal glycogen with short outer chains, hypoglycemia
  473. Andersen's disease
    deficiency in Branching enzyme-->abnormal glycogen, having long unbranched chains, early death due to cardiac and liver failure
  474. Her's disease
    Deficiency in liver glycogen phosphorylase-->abormally high content in liver glycogen, mild hypoglycemia and ketosis
  475. How are glycogen storage diseases treated?
    Dietary restrictions (high protein, low carb)
  476. Complement cascae
    opsonization, phagoctosis, recruitment of other inflammatory cells, MAC complex
  477. C3 convertase
    involved in all 3 complement pathway
  478. 4 plasma mediated systems
    Kinin, clotting, fibrinolytc, and complement
  479. Coagulation cascade
    Intrinsic and extrinsic involvve Factor X-->produces soluble fibrin
  480. Plasmin iniaties degradation
    To break down fibrin you use fibrinolytic pathway
  481. Coagulation cascade
    Intrinsic and extrinsic involvve Factor X-->produces soluble fibrin
  482. To break down fibrin you use fibrinolytic pathway
    Plasmin iniaties degradation
  483. 4 plasma mediated systems
    Kinin, clotting, fibrinolytc, and complements
  484. Factor XII
    is synthesized in the liver: Hageman factor, Involves the cleavage of a few peptide bond to activate the clotting cascade and the kinin cascade
  485. Acute inflammation
    minutes to day, rapid onset, neutrophils (last 2-3 days in tissue), restoration
  486. Chronic inflammation
    weeks to years, prolonged duration, macrophages and lymphocytes (B and T cells), angiogenesis
  487. Conditions associated with chronic inflammation
    cardiovascular disease, obesity, type II diabetes, chrons disease
  488. Innate Immunity
    always present, always present, neutrophils and macrophages, natural killer cells
  489. Adaptive Immunity
    Normally silent, componets are lymphocytes (B and T), B lymphocytes generate antibodies and T lymphocytes, cytokines
  490. Libby research on chronic inflammation
    involves innate and adaptive immune system
  491. The two cell types in inflammation
    epithelial and mesenchyma; ce;;s
  492. Main cytokines in chronic inflammation
    TNF, IL-1 IFN-gamma
  493. Inflammation in response to LDL
    macrophages have a huge amount receptors for oxidized and glycated LDL
  494. Adaptive connects to innate immunity
    T helper cells release IFN-gamma and signals MF to send signals to pro-inflammatory cytokines
  495. monounsaturated fats
    lower LDL, do not lower HDL (olive oil, walnut oil, avocado)
  496. polyunsaturated fats
    lower LDL but also lower HDL (fish oil)
  497. Omega-3 unsaturated fats
    type of polyunsaturated fat, helps reduce the triglycerise
  498. saturated fats
    BAD! Increase LDL cholesterol
  499. Mediterranean Diet
    Leads 23% decreased of death risk, high fruit, potato, beans, nuts, seeds, whole grain bread, olive oil, wine, little dairy
  500. PGE1 and PGE3
    the less inflammatory prostalgin
  501. PGE2
    fever inducing prostaglandin
  502. Pyridoxal-P
    enzyme that participates in the cleavage reaction for glucogen phosphorylase
  503. TPP deficiency
    genetic defect, lacking TPP then you can't convert Pyruvate-->acetyl CoA, causes lactic acidosis
  504. B vitamin deficiency
    alcoholics and anorexia
  505. In protein turnover
    All amine groups ge converted to Glutamine or urea
  506. What causes negative nitrogen balance
    starvation, uncontrolled diabetes, infection, trauma
  507. What causes positive nitrogen balance
    pregnancy, lactation, growth
  508. Marasmus
    deficiency in proten and calories (chronic)
  509. Kwashirokor
    deficiency in protein (onset precipitated by increased demand) not necessarily lacking in diet could be inability in protein synthesis
  510. Major differences between Kwashiorkor and Marasmus
    Marasmus has muscle wasting, albumin is moderately diminished and no body fat, Kwashiorkor has Edema and Hepatomegaly in still has some body fat, severely diminished serum albumin, normal insulin and cortisol levels
  511. What do transaminases use as an amino acceptor?
  512. Maple syrup urine disease
    autosomal recessive, Deficiency in BCKA DH, so you can't degrade BCAAs, you get elevation in BCAAs, keto-acids and alpha-hydroxyacids in urine, vomiting lethargy, severe brain damage
  513. BCL2
    anti-apoptotic protein, homologue of ced9, BCL2 is associated with mito and somehow associated with blocking the release of cytoC, overexpression in B Cell lymphoma
  514. BCL2 family
    there are two types of proteinsin the BCL family, BH3 only and BH3+other, can be pro or anti apoptotic
  515. caspases
    proteases responsible for apoptosis, analogue in C. elegans is ced-3 (but in humans there are 14 different caspases), they are cystein dependent aspartate directed proteases AspHole, exist as zymogen activated by cleavage
  516. What activates caspases
    Apaf-1 (ced-4 homologue), ATP, cytochrome C (comprise the apoptosome)-->this starts the activation of the initiator caspase 9
  517. BAX
    pro-apoptotic, in the BCL family-->cause the release of cytoC
  518. Pro-apoptotic proteins
    put the helical tail in the active site, sterically occluding their own active site (like CDKs), and inactivating them
  519. Anti-apoptotic proteins
    have an open, hydrophobic BH3 pocket, and are active
  520. In cell undergoing apoptosis
    Hydrophobic pocket is occupied by the BH3 domain of a pro-apoptotic, frees up the pocket of pro-apoptotic protein-->get apoptosis
  521. Megaloblastic anemia
    caused by a dietary deficiency of folate or B12
  522. Warfarin
    Cyp 2C9
  523. Aerobic glycolysis generates
    2 pyruvate, 2NADH, 2ATP
  524. Anaerobic glycolysis generates
    2 lactate and 2 ATP
  525. What enzyme in glycolysis requires NAD+
  526. Lactate dehydrogenase
    used NADH to convert pyruvate to lactate-->generates NAD+
  527. Physical inactivity leads to a _________ in protien synthesis
    decrease (50% by 14 days)
  528. Stress/burn/trauma leads to a ___________in protein synthesis, a ________ in protein degradation, with an overall net________
    increase in synthesis, increase degradation, overall net decrease in protein
  529. Physical inactivity leads to a ______________ protein balance
  530. Stress/trauma/burn leads to a ________________ protein balance
  531. Cortisol generates a _______________ response of muscle
  532. Cortisol cause _____________ in blood sugar resulting in _____________
    increase, hyperglycemia
  533. Stress response in burns results in patients being ____________
  534. Branched chain amino acid (BCAA) transaminase
    converts (valine, leucine, isoleucine) BCAA-->BCKA
  535. Branch chain ketoacid (BCKA) dehydrogenase
    converts BCKA to BCKA analogues (propionyl CoA, acetyl CoA, acetoacetyl CoA)
  536. To ameliorate loss of lean body mass in bedrest supplement with_________
    essential amino acids
  537. Hemolytic anemia caused by deficieny in _________________, blood smear includes_____________
    G6P DH, Heinz bodies
  538. G6P DH
    most common human enzymes deficiency
  539. G6P dehydrogenase
    PPP, converts G6P-->phosphogluconolactone, IRREVERSIBLE
  540. Lactonase
    converts 6-phosphogluconolactone-->6-phosphogluconate, IRREVERSIBLE
  541. 6-phosphoglucanate dehydrogenase
    converts 6-phosphogluconate--> ribulose 5-P
  542. Carnitine enzyme deficiencies
  543. PPAR-alpha
    transcription factos for fatty acid oxidation, targeted by Fibrates--fibrates are a PPAR agonist
  544. Beta-oxidation chain enzymes
  545. Most common beta-oxidation enzyme deficiency
    MCAD, on exon 11
  546. Mitochondrial trifunctional protien
    HADHA alpha subunit, HADHB beta subunit, LCHAD on HADHA
  547. LCHAD activity
    involved in HELLP syndrome, on the HADHA alpha subunit
  548. HELLP
    hemolysis, elevated liver enzymes, low platelets, LCHAD deficiency in the toxic baby
  549. Treatment fo rmitochondrial beta oxidation disorders
    mostly nutritional, goal to stabilize day to day, avoid catabolic events
  550. If have VLCAD deficiency
    Try to supplment diet with medium-chain triglycerides
  551. SCAD deficiency symptoms
    can't stay warm because these control the white/brown fats
  552. Anaplerosis and metabolic therapy
    anabolic process, replenishing the pool with odd chain FAs
  553. what is the rate limiting enzyme in bile synthesis
    7-alpha hydroxylase (CYP7A1)
  554. What do bacteria use to convert primary bile acids to secondary bile acids?
  555. Bile secretion is controlled by hormones
  556. How are steroid hormones are excreted?
    after pre-processing in the liver--> excreted via the kidney in the urine
  557. What kind of binding domain to steroid hormones use?
    zinc finger (2 zinc fingers because recptors dimerize
  558. How do steroids act once in the cell?
    steroid hormones bind to receptor which binds specific response elements (transcription factors)
  559. How do steroid zinc fingers differ from standard?
    have 3 cysteine residues instead of 2 cysteine 2 histidine
  560. Are steroid receptor motfis (DNA binding domains) are conserved?
  561. Insulin synthesis
    Pancreatic beta cells-->formed as pre-proinsulin-->signal peptide cleaved-->proinsulin-->C-protein cleaved-->insulin
  562. What organelle synthesizes insulin
    RER of pancreatic Beta cells
  563. What is a good marker for Beta-cell function?
  564. How is insulin release in Beta cell?
    Glucose comes in through GLUT2-->phosphorylated by Glucokinase-->increase in ATP--> close ATP-gated K channel-->depolarizes cell--> Opens Ca2+ channels-->triggers release of insulin
  565. What aminoacids stimulate insulin?
    leucine, arginine, lysine
  566. GI hormones that potentiate insulin secretion
    GIP, cholecystokinin (also signals release of bile), GLP-1, and VIP
  567. In severe hypoglycemia why is there a higher oral glucose repsonse than IV?
    Because IV would bypass the GI hormones that potentiate insulin secretion
  568. How are GLUT4 receptors recruited to cell membrane?
    glucose binds insulin receptor--->tyr-kin-->IRS-->GLUT 4 brough to membrane
  569. Insulin does what to potassium levels in cells?
    increases K uptake in cells
  570. Insulin resistance is due to
    post-receptor signaling transduction defects, defective insulin signaling
  571. This mineral plays an important yet indirect role in antioxidant function as part of glutathione peroxidase
  572. Increasing intake of this mineral can help offset the negative effects of a high sodium intake
  573. Vitamin that humans and primates are among the few mammals that can't synthesize
    Vitamin C
  574. Niacin can be made in the liver from which amino acid high in turkey
  575. Newborns are given a shot of this vitamin at birth
    Vitamin K
  576. This vitamin is the leading cause of blindness worldwide
    Vitamin A
  577. Pantothenic acid is part of this compound that is common in the metabolism of three energy producing macronutrients
    Acetyl CoA
  578. To assess riboflavin status the activity of erythrocyte glutathione reductase is measured because it requires this coenzyme
  579. Vitamin important in most carboxylase reactions of metabolism
  580. Status of this vitamin can be assessed by measuring transketolase activity in the erythrocyte
  581. This vitamin helps to keep homocysteine levels down
    Folic acid- B12 (homocysteine+methylTHF-->mehtionine +THC)
  582. This vitamine prevent free radical damage by donating its hydrogen ion to the free radical
    Vitamin E
  583. This vitamin is derived from a steroid
    Vitamin D
  584. This vitamin plays an important role in blood clotting
    Vitamin K
  585. Supplement companies might promote vitamin C as a "fat burner" because it is the key reducing agent in this carrier
  586. This vitamin has been used to treat hypercholesterolemia
  587. Supplements can not exceed 400mcg of folate because megadoses of folate mask a deficiency in this vitamin
  588. Elderly patients and anyone with suppressed stomach acid secretion may lack intrinsic factor and will therefore need a supplement of this vitamin
  589. Vegan who consumes no fortified food products is at greatest risk for this vitamin deficiency
  590. Unlike most water soluble vitamins, this one can be stored in the body for long periods of time
  591. Sodium is added to sports drinks to prevent this condition often experienced by long distance athletes
    Hyponatremia- people drink lots of water, but not sodium, also gives credit for electrolytes
  592. Because of its role in improving insulin function, this mineral supplement is said to increase lean body mass
  593. Due to its role in muscle contraction, many people takes this mineral supplement to help prevent muscle cramps during exercise
  594. If you over cook your vegetables you may lose this entire class of vitamins
    Water soluble/B vitamins are susceptible to damage by high heat while cooking
  595. Vitamin C is often added to food as a preservative because of its role as this
  596. This water soluble vitamin part of electron carried FAD is damaged easily by light and explains why milk is not packaged in clear bottles
  597. Every amino acid transaminase or decarboxylase requires this B vitamin
    Pyridoxine B6
  598. What enzyme requires Pyridoxal P?
    glycogen synthase and transaminase
  599. This macro mineral is part of ATP
  600. A vitamin made from cholesterol
    Vitamin D
  601. Beri Beri is caused by a lack of this water soluble vitamin
  602. Vitamin C is often added to food as a preservative because of its role as this
    Because of its role as an antioxidant
  603. A patient reports complaining of shortness of breath when exercising and all over fatigue. This is the first disease to look into
  604. Megaoblastic anemia
    deficiency in B12-->prevents production of folate
  605. Wilsons disease is an autosomal recessive disease leading to accumulation of this mineral/metal (part of cytochrome c oxidase) in the liver and brain