Term
| Glucose-6-Phosphate can be metabolized via what three mechanisms? |
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Definition
| Glycolysis, Glycogen Synthesis, and the Pentose Phosphate Pathway |
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Term
| What is the oxidative reactions of PPP? |
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Definition
Glucose->6-Phosphogluconate
via Glucose-6-Phosphate dehydrogenase
6-Phosphogluconate -> Ribulose-5-phosphate
these reaction are irreversible
via 6-phospho-gluconate dehydrogenase |
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Term
| What is the rate limiting step of PPP? |
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Definition
Glucose -> 6-Phospho-gluconate
via Glucose-6-phosphate dehydrogenase |
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Term
| What are the two intermediate products that can be made in PPP after the production of Ribulose-5-phosphate? |
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Definition
| Ribose-5-phosphate or Xylulose-5-phosphate |
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Term
| What is Ribose 5-phosphate used for? |
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Definition
| Synthesis of nucleic acids |
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Term
| What is Xylulose 5-phosphate used for? |
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Definition
| Can be turned into Glyceraldehyde-3-phosphate which is then used for Glycolysis |
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Term
| What enzymes drive PPP towards glycolysis? |
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Definition
| Transketolase and Transaldolase |
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Term
| What does transketolase do? |
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Definition
| Transketolase abstracts two carbons from Xylulose-5-phophate and adds it to either Ribose-5-phosphate or Erythrose 4-phosphate. The resultant products are Glyceraldehyde-3-phosphate (glycolysis) and Sedopheptulose-7-phosphate or Fructose-6-phosphate (glycolysis) |
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Term
| What does transaldolase do? |
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Definition
| Transaldolase abstracts 3 carbons from sedoheptulose-7-phosphate and adds it to Glyceraldehyde-3-phosphate. The resulting products are Fructose-6-phosphate (glycolysis) and Erythrose 4-phosphate |
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Term
| How is Glucose-6-Phosphate dehydrogenase regulated allosterically? |
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Definition
Activity is diminished with increased quantities of:
NADPH
ATP
Oxidized Glutathione |
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Term
| What are the important byproducts of the oxidative steps of PPP? |
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Definition
| Ribulose-5-phosphate and NADPH (2) |
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Term
| What hormones/secondary messengers affect the activity of Glucose-6-phosphate dehydrogenase |
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Definition
| Insulin and PKA/PKC/Src Kinase all phosphorylate and increase the activity of Glucose-6-phosphate dehydrogenase |
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Term
| What important physiologic functions does NADPH perform? |
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Definition
Reductive biosynthesis for fatty acids and steroids
Reduction of hydrogen peroxide (free radical promoting molecule)
Co-factor for Cytochrome P450 monooxygenase
Phagocytosis by white blood cells
Synthesis of nitric oxide |
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Term
| How does NADPH play a role in reducing levels of H2O2? |
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Definition
| NADPH is a cofactor for the enzyme GSH-reductase (Glutatione reductase). This enzyme reduces dimers of Glutathione. This is important as the reduced form of Glutathione is used in a reaction (catalyzed by Glutathione peroxidase) that transforms the dangerous H2O2 into water |
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Term
| What is the action of Cytochrome P450 monooxygenase? |
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Definition
| Cytochrome P450 monooxygenase (of which NADPH is an important cofactor) hydroxylates steroids and detoxifies foreign compounds |
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Term
| Why is NADPH important in the phagocytosis that white blood cells engage in? |
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Definition
| NADPH (reducing agent) donates an electron to O2 making Super Oxide. Super Oxide can perforate and destroy bacterium by itself or through hydrogen peroxide |
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Term
| How is NADPH an important cofacter for the synthesis of Nitric Oxide? |
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Definition
| NADPH is consumed (product NADP+) by the enzyme NO synthase in NO synthesis |
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Term
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Definition
| NO plays important roles in: relaxation of smooth muscle, prevention of platelet aggregation, as a neurotransmitter in the brain, and as a mediator of tumorcidal and bactericidal actions of macrophages |
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Term
| Genetically speaking, what kind of disease is seen in PPP deficiency? |
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Definition
| X-linked disease in which the action of Glucose-6-phosphate Dehydrogenase is diminished |
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Term
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Definition
| Aggregate proteins that appear as distinctive red spots on blood cells. These proteins aggregate as a result of damage from oxidative stress |
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Term
| What sort of pathology is characteristic of a patient suffering from Glu-6-PDH deficiency, assuming oxidative stress? |
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Definition
| Hemolytic anemia and heinz bodies |
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Term
| How many classes of Glucose-6-phosphate dehydrogenase deficiency exist and how are they classified? |
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Definition
4 classes
I: less than 2% activity
II: less than 10% activity
III: between 10-60% activity
IV: greater than 60% activity
as the activity goes down the clinical presentation gets worse. Class IV has no discernible symptoms |
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Term
| Given Mediterranean G6PD deficiency, how long do RBC's have G6PD activity? |
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Definition
|
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Term
| Given G6PD A- deficiency, about how many days does the RBC have enzyme activity? |
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Definition
|
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Term
| What sort of factors can put RBC's into oxidative stress? |
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Definition
| Fava bean (favism), Oxidant drugs, Infection |
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Term
| What are examples of Oxidant drugs? |
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Definition
Antibiotics: sulfamethoxazole and cloramphenicol
Antimalarials: primaquine
Antipyretics: acetanilid |
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Term
| What clinical presentation can a neonate with G6PD deficiency have? |
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Definition
| Jaundice from increased production of bilirubin |
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Term
| What is the disease that results in a lowering of transketolase activity? |
|
Definition
| Wenicke-Korsakoff Syndrome |
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Term
| What is the presentation of Wenicke-Korsakoff Syndrome? What is a vulnerable population? |
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Definition
Patients present with severe memory loss, mental confusion, and partial paralysis.
Common in alcoholics |
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