Flashcards in EXAM3_WS5_Metabolism_Cases Deck (17)
What is Glutathione ?
Glutathione is derived from what 3 AA's?
How does G6PDH deficiency affect glutathione?
amount of glutathione stays the same but they can't be reduced and cannot function
(decreases how many glutathiones are reduced)
Pyruvate kinase deficiency affects glutathione how?
Decreases synthesis of glutathione so there is less available to detoxify ROS
G6PDH deficiency is the most common defect worldwide. 10% of population but they don't know it. Why?
Pathology only expressed under oxidative stress to erythrocytes (thought to be defense against malaria)
Typical G6PDH deficient patient expresses less than 60% of G6PDH activity and only manifests symptoms when subjected to oxidative stress. Why?
These conditions cause rise in H202 due to decreased levels of NADPH able to reduce glutathione
Heinz Bodies are expressed in what disorder?
G6PDH deficiency- oxidized and precipitated Hb bound to the plasma membrane lipids
Causes Hemolytic anemia/ jaundice b/c removed by spleen
What increases oxidative stress?
Infections (macrophages use H202)
Antibiotic Bactrim (drugs)
Pyruvate Kinase (PK) deficiency in RBC's
Decreases ATP (RBC's only have glycolysis)
PREMATURE RBC DESTRUCTION= ANEMIA
What is worse PK or G6PDH deficiency? Why
PK b/c its chronic anemia
G6PDH deficiency is in all cells (PK is only in RBCs) why then does it only affect RBC's?
RBC's don't have mitochondria and rely on HMP shunt oxidative branch for NADPH (reduced by G6PDH deficiency)
Other cells have mitochondria and can use MALIC enzyme to make NADPH and can continue to reduce glutathione
PK impairs ATP while G6PDH impairs NADPH what impact does each have on glutathione levels and oxidized:reduced ratio of glutathione?
G6PDH increases oxidized:reduced ratio
PK decreases actual glutathione ratio
Ethanol oxidation in the cytosol (2 rxns)
both result in increased NADH
Chronic Ethanol oxidation in the SER (microsomes)
CYP2E1 and CYTP450
CYP2E1 Oxidizes NADPH in SER
Ethanol metabolism increases cytosolic NADH and two reactions are forced in order to regenerate NAD+. What are the two reactions used to regenerate NAD+?
1. Pyruvate > Lactate
2. OAA > Malate
the gluconeogenic intermediates are decreased resulting in profound Hypoglycemia
can produce lactic acidosis
What is the role of thiamine in glucose oxidation? and what metabolic processes will slow as a result?
Thiamine is precursor for TPP
TPP required by PDHC and aKGDH
Why comatose alcoholics may develop lactic acidosis after infusion with dextrose without thiamine?
Alcohol inhibits thiamine absorption (alcoholics may be thiamine deficient)
PDHC inhibited results in pyruvate accumulation in cytosol.
NADH from alcohol metabolism accumulates in cytosol
This forces LDH to make LACTATE to regenerate NAD+