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cjharmon311
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What are the two causes of hemolytic anemia?
- Glucose-6-P Dehydrogenase Deficiency
- RBC-specific Pyruvate Kinase Deficiency
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What are the three sources of oxidant stress in G6PD deficiency?
- infections (macrophages produce hydrogen peroxide)
- oxidant drugs (produce oxygen free radicals)
- fava beans (stimulate production of hydrogen peroxide)
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In cells with mitochondria how is NADPH produced?
NADPH is produced from the HMP-shunt oxidative branch and via malic enzyme.
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In tissue without mitochondria how is NADPH produced?
HMP-shunt oxidative branch only
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How does pyruvate kinase deficiency lead to hemolytic anemia?
PK deficiency=no ATP=no glutathione production=no oxidation of hydrogen peroxide (increased concentration of hydrogen peroxide)=membrane rigidity of RBC because of spectrin=premature destruction by spleen=hemolytic anemia
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What mechanism do RBCs use to compensate for low levels of Hb?
2,3 BPG, which decreases RBCs affinity for oxygen so more oxygen is getting to the tissues (this reduces ATP production even more because the shunt to 1,3 BPG take out a path to make ATP)
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A person with congenital NADH-cytochrome b5 reductase deficiency should avoid what compounds/foods?
Nitrates and nitrites (NO2-, NO3-) because they increase the amount of methemoglobin
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What two enzymes oxidize ethanol in the cytosol?
alcohol dehydrogenase and aldehyde dehydrogenase
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Which enzyme in the SER oxidized NADPH and ethanol after chronic ingestion of ethanol?
CYP2E1 enzyme, followed by aldehyde dehydrogenase
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How does the liver get rid of high amount of NADH after ethanol ingestion?
- 1. malate-asparate shuttle (OAA to malate direction)
- 2. glycerol-3-P shuttle
- 3. Pyruvate to lactate by LDH (when the shuttles are saturated
- Note: gluconeogenesis is greatly reduced, leaving profound hypoglycemia
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What is the relationship between thiamine and glucose oxidation?
Thiamine is a precursor of TPP, which is required by enzymes that participate in complete glucose oxidation like PDHC, and alph-ketoglutarate dehydrogenase
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Why do alcoholics develope localized cerebral lactic acidosis after glucose infusion when thiamine is not present?
Pyruvate and NADH accumulate from reduced PDHC and ethanol oxidation, LDH convert pyruvate to lactate and NADH to NAD+
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