Biochemistry Mini1 Part2

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  1. Diisopropyl Phosphofluridate
    • irreversible acetylcholinesterase
    • overactivation of the parasympatheic pathway
    • similar to organo-phosphate poisioning
  2. Allopurinol
    • Xanithine Oxidase inhibitor
    • Prevent the breakdown of hypoxanthine to Urate
    • Allievation of gout/uric acid poisoning
  3. Malonic Acid
    • Competitive inhibitor of succinate dehydrogenase
    • displacing succinic acid
  4. Ethanol
    competitive inhibitor of alcohol dehydrogenase for methanol
  5. Fomepizole
    • competitive inhibitor of alcohol dehydrogenase
    • used for methanol and ethanol poisoning
    • does not produce formaldehyde products which are poisonous to occular nerve
  6. Ki of competitive inhibitors
    • the lower the Ki(Km of inhibitor) compared to the Km of the original (k-1/k1) substrate the more competitive the drug is for the inhibition of the ES complex
    • instead forms EI complex
  7. Competitive vs none competitive inhibition
    Km change in competitive and Vmax change in none competitive
  8. Homotropic allosteric effectors
    • substrate binding changes the enzyme kinetics
    • hemoglobin binding to oxygen is considered homotropic
  9. Lysozomal Peptidoglycan hydrolysis
    • breaks NAM-NAG repeats in bacterial wall
    • lysis of glycosidic bonds (2 sugars in this case)
    • Glutamate and Aspartate catalytic peptides
  10. Chymotrypsin
    • Serine-protease (serine lead bond breaking)
    • his, asp, ser catalytic triad
    • break down peptide bonds
    • trypsin and elastase in the same family
  11. Carbonic anhydrase
    • H2O+CO2<--> H2CO3
    • bicarbonate buffer system
    • binds metals
    • conversion of CO2 to carbonic acid (intermediate)
    • inhibitor Acetazolamide can treat glacoma and respiratory alkidosis by increasing CO2 levels in body
  12. HMG-CoA Reductase
    • Cholesterol biosynthesis
    • end stage of beta hydroxylation
    • over production of cholesteral in familial hypercholesterolemia
    • Inhibitor of statin
  13. Acetylcholinesterase
    • gets ride of your aceytlchoine into choline and acetate with water
    • inhibitors are poisons (organophosphates fasciculin-II, diisopropyl phosphofluridate)
  14. G1 Check point
    • Cyclin D+ CDK4/6 act.
    • Cyclin E+ CDK2 act
    • S - phase
  15. G2 Check point
    • Cdc25 act
    • CDK1
    • Cyclin A+CDK1 act
    • Cyclin B
    • Cyclin B + CDK1 act
    • Mitosis Promoting Factor
  16. Metaphase - Anaphase check point
    • Sister chromatid seperation using seperase
    • Cdc20 act
    • APC tagging
    • securin for ubiquitinalytion
    • seperase free to cut cohesin
  17. Phosphofructokinase-1
    • PFK1 phosphorolates fructose 6-phosphate
    • committs sugar to glycolytic pathway
    • add the 2nd ATP to the sugar molecue
  18. hexokinase (glucokinase)
    • adds first ATP to sugar
    • hexos version does all sugars with low Km
    • Gluco version in liver is only for glucose and has high Km compared to hexos, will not be saturated and only kicks in when there is EXCESS glucose
  19. Glyceraldehyde 3-phosphate DH
    • Adds 1 PiH to each of the two glyceraldehyde 3-phosphate WITHOUT using ATP
    • produces 1,3 bisphospholycerate
    • NAD+ is reduced to NADH
    • NADH is used eithe rin oxidative phosphorylation or anarobic respiration of pryruvate to lactic acid
    • 3rd and last Pi addition to sugar substrate
    • now you have 2 bisphosphates each with 2 Pi's
  20. Phosphoglycerate Kinase
    • PGK - produces the first ATP of glycolysis
    • taking the Pi that we just put on with GAPDH
    • first pay off
  21. Pyruvate kinase
    2nd and last substrate level phosphorylation (not linked to eletrcon transport chain)
  22. Glycolysis Net
    • 2ATP (added 4Pi but only 2 cost ATPs and took off 4Pi)
    • 2NADH
    • 2 pyruvate
  23. Cori Cycle
    • Gluconeogensis at liver
    • makes glucose from lactate
  24. Glycolysis regulation
    • PFK-1 negativly regulated by ATP allocsticly
    • increases Km while not affecting Vmax
    • AMP lowers Km
  25. ATP/AMP regulation
    • negative for PFK and PK - ATP
    • pos for PFK and PK - AMP
  26. None glycolysis substrate regulation of glycolysis
    • F2,6BP regulates PFK-1 by reducing its Km
    • insulin/glucogon --> phosphorylation of PFK-2 --> phosphorylates F6P to F2,6BP(not a part of glycolysis) --> decreases Km for PFK-1
  27. High NADH
    • Results from alcohol metabolism
    • inhibits citric acid cycle, gluconeogensis and fatty acid oxidation
    • promotes fatty acid synthesis in liver
  28. Ethanol Metabolism
    • Alcohol dehydrogenase
    • aldehyde dehydrogenase
    • produce high energy NADH and acetate
    • drive motabosim towards ketone bodies and fatty acids
  29. PKA and cAMP in Glycolysis
    in liver and adipose cells
    • Control molecues
    • ↓insulin ↑cAMP ↑PKA↑PFK-2 activity ↓F2,6BP↓PFK-1 activity ↓ glycolysis

    vise versa
  30. PKA/PFK-2 in cardiac muscle
    similar ↑ cAMP will ↑PKA BUUUT ↑ PFK-2 KINASE activity ↑F2,6BP ↑PFK-1
  31. PFK-2
    • PKA phosphorylation to change activity
    • phosphorylate --> phosphatase in liver cells
    • phosphorylate --> kinase in cardiac muscles
  32. Pyruvate Kinase Regulation
    • ↑ATP/Ala ↓ PK
    • ↑PEP ↑PK
    • ↑F-1,6,P2 ↑PK
    • ↑cAMP ↑PKA ↓PK -similar to liver glycolysis to conserve glucose during fasting or energy need
  33. Hemolytic anemia
    hexokinase deficiency in erythrocyte
  34. Pyruvate kinase deficiency
    • hemolytic anemia, pallor, jaundice, ulcers
    • due to hemolytic issues, enlarged speen, low RBC
    • low ATP with elevated 2,3,BPG
    • genetic disorder for isozyme of PK in RBC
  35. E2F
    • grows
    • inactive E2F-Rb form
    • activated by CyclinD+Cdk4/6
    • E2f free form produces Cyclin E
  36. Cyclin E
    • promoted by free E2F
    • with Cdk2 -> goes into S phase
  37. Cdc20
    • chromatid stress produced
    • activates APC
    • with cdc14 dephosphorylate seperase to activate
  38. APC - cell regulation
    • APC ubiquitinalytes securin
    • releases seperase
    • seperase still phosphorylated(inactive, needs Cdc 20/14)
  39. Seperase
    • regulated by amount of Cdc20 through APC
    • inactive bound to securin
    • active cleave cohesin --> anaphase
  40. G2-M regulation
    • Cdk 1 activity:
    • activated by Cdc25 and deactivated by WEE-1
  41. Mitosis promoting factor
    • Cdk-1 + Cyclin B
    • Cdk activation by Cdc25
    • Cyclin B activation by Cdk1+Cyclin A
  42. p53
    • p53 kills (tumor necrosis factor)
    • inactive if bound to mdm2
    • alone it promots apoptosis
  43. Alcohol Metabolism
    • Alcohol dehydrogenase (requires NAD+)
    • --> acetal-adyhyde
    • Acetalaldyhyde dehydrogenase
    • -->acetic acid
  44. Alcohol inhibition of gluconeogenisis
    • Alcohol degradation eats up NAD+ and pyruvate
    • Both are needed for pyruvate carboxylase, rate limiting step of gluconeogenisis
Card Set
Biochemistry Mini1 Part2
Biochemistry Mini1 Part2
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