-
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
-
Methanol
Poisoning
- -MeOH >[alc.
- Dehyd] > formaldehyde>>formic acid (causing metabolic acidosis)
-vision impairment
-
Ethylene
Glycol Poisoning
- -Ethylene glycol
- (ROH) > [alc dehyd] > glycoaldehyde>>glycolate
- -glycolate-
- interferes with hepatic enzymes, metabolic acidosis
- -Absorbed by GI
- tract, metabolized by liver
-
Genetic
defects in Glycolysis
Glycolytic Enzymes:
- -complete deficiency
- = fatal
- -partial deficiency
- = hemolytic anemia
-
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
-
Pyruvate
Kinase Deficiency
- -affected isoform
- only found in erythrocyte
-
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
-
Mercury
& Arsenite poisoning
- -bind to
- dihydrolipopoyl group of pyruvate dehyd. And leads to CNS pathologies
- -lack of acetyl co A
- --> decreased acH neurotransmitter
-
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
-
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
-
Cornea
& Lens
- -tissue is
- transparent b/c no blood vessels
- -lens has no
- mitochondria so obtains glucose from vitreous and aqueous humor
-
Kidney
Medulla
- -cortex has lots of
- blood vessels
- -medulla doesn’t
- have a lot of blood vessels and therefore depends on anaerobic glycolysis
-
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
-
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)
-
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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