BCHM Glycolysis Diseases

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sketch112
ID:
67453
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BCHM Glycolysis Diseases
Updated:
2011-02-19 13:38:10
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Glycolysis
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Description:
SGU Term 1 BCHM
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  1. Ethanol
    Metabolism
    • Disulfirma binds
    • irreversibly to aldehyde dehydrogenase, preventing the conversion of
    • acetalaldehyde to acetic acid, and therfore it buildsup in tissue, causing
    • vommiting and alcohol avoidance:

    • Ethanol > [alc.
    • dehyd.] > acetylaldehyde > [ald. Dehyd] > acetic acid
  2. Methanol
    Poisoning
    • -MeOH >[alc.
    • Dehyd] > formaldehyde>>formic acid (causing metabolic acidosis)

    -vision impairment
  3. Ethylene
    Glycol Poisoning
    • -Ethylene glycol
    • (ROH) > [alc dehyd] > glycoaldehyde>>glycolate

    • -glycolate-
    • interferes with hepatic enzymes, metabolic acidosis

    • -Absorbed by GI
    • tract, metabolized by liver
  4. Genetic
    defects in Glycolysis
    Glycolytic Enzymes:

    • -complete deficiency
    • = fatal

    • -partial deficiency
    • = hemolytic anemia
  5. Pyruvate
    Kinase deficiency & hemolytic anemia
    -RBCs totally dependent on mitochondria

    • -cells swell and lyse without ATP (and Na.K+ pump
    • cant be maintained)

    • *note- reticulocytes
    • (immature RBC) don’t have PK, but have mitochondria so can get ATP via ox phos
  6. Pyruvate
    Kinase Deficiency
    • -affected isoform
    • only found in erythrocyte

    • -fatal in less than
    • 5%
  7. Arsenic
    poisoning
    • -trivalent form
    • extremely toxic

    • -enzymes usuing
    • lipoic acid as cofactor are susceptable

    • -arsenate
    • pentavalent form competes for Pi bindg sites producing unstable esters
  8. Mercury
    & Arsenite poisoning
    • -bind to
    • dihydrolipopoyl group of pyruvate dehyd. And leads to CNS pathologies

    • -lack of acetyl co A
    • --> decreased acH neurotransmitter
  9. Arsenate
    & Glycolysis
    • -normal: glyceraldyde 3 phosphate
    • -->[glyceraldehyde 3 phosphate dehyd.] --> 1,3 bisphosphoglycerate

    • -arsenate can make
    • it form 1-arseno-3phosphoglycerate --> 3 phosphoglycerate + arsenate

    • --glycolysis
    • continues but at the expense of one less ATP
  10. Dental
    Caries (tooth decay)
    • Sugar forms plaque
    • on teeth and anaerobic conditions in mouth cause production of lactate and
    • pyruvate that degrade tooth enamel

    • -flouride- hardens
    • enamel, inhibits bacteral growth by inhibiting enolase by minding to Mg2+ +
    • phosphate
  11. Cornea
    & Lens
    • -tissue is
    • transparent b/c no blood vessels

    • -lens has no
    • mitochondria so obtains glucose from vitreous and aqueous humor
  12. Kidney
    Medulla
    • -requires a lot of
    • ATP

    • -cortex has lots of
    • blood vessels

    • -medulla doesn’t
    • have a lot of blood vessels and therefore depends on anaerobic glycolysis
  13. Neonatal
    tissues
    • -fetus depends on
    • glucose and ketone bodies

    • -during placental
    • separation, hypoxic condiitons anaerobic glycolysis is required

    • -hepatic glycogen
    • concentration highest at end of pregnancy
  14. Glucose-6-P
    dehydrogenase deficiency
    -x linked disease

    • -leads to NADPH
    • deficiency in RBCs --> hemolytic anemia

    • -can be caused by
    • oxidants, drugs, favism (beans), infection, neonatal jaundice

    • -RBCs vulnerable to
    • oxidant injury (normally neutralized by reducing glutathione)
  15. Cancer
    • -tumors have
    • enhanced rate of glucose uptake and glycolysis (even though they have
    • mitochondria)

    • -cancer cells grow
    • faster than blood vessels (hypoxia effect)

    • -tumor cells
    • synthesize hypoxia-injducible transcription factor (HIF-1) during such
    • conditions

    • -HIF-1: increases
    • expression of glycolytic enzymes and GLUT 1 and 2

    • Increases
    • blood vessel growth

    • Activated
    • by anaerobic exercise

    • -cancer treatment:
    • block production of HIF1

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