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33 Cards in this Set
- Front
- Back
What are folates converted to inside the intestinal lumen?
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Folic Acid Monoglutamate
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How are folates taken up by the enterocytes of the intestinal lumen?
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They bind to Folate Binding Protein and are entocytized
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What happens to folic acid once it is taken up by the enterocytes of the intestinal lumen?
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It is reduced to DHF, and then to THF. It is then methylated to form N5-methyl-THF before being released into the bloodstream
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How do peripheral cells take up Folate
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Via Folate Binding Protein
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What happens to N5-methyl-THF once taken up by peripheral cells?
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It is converted to THF and glutamate residues are attached to it to help trap it inside the cell.
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What enzyme attaches glutamate residues onto THF?
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Folylpolyglutamate Synthase
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How are one carbon groups transported from the cytoplasm into the mitochondria?
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N5/N10-methylene-THF transfers a 1-carbon group onto glycine and becomes serine. Serine enters the mitochondria and transfers that 1-carbon group onto THF to form N5/N10-methylene THF.
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How is methanol metabolized?
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Methanol is converted to formaldehyde (alcohol dehydrogenase). Formaldehyde is converted to Formic Acid (Formaldehyde Dehydrogenase). Formic Acid is converted to N10-formyl-THF and then C02
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If methanol is metabolized to C02, why does methanol poisoning occur?
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The rate of reaction for Formic Acid to N10-formyl-THF and then to C02 is very slow so Formic Acid builds up leading to acidosis.
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What are the 3 treatment options for methanol ingestion?
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1) Induce emesis (vomiting)
2) Drink/infuse ethanol 3) Fomepizole (inhibitor) |
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What are the two damaging intermediates of Ethylene Glycol metabolism?
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Glycolate
Oxolate |
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What are their specific damaging effects on the body?
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Glycolate = Damages Kidney tubules
Oxolate = binds Ca++ causing hypocalcemia, forms Ca-oxolate crystals damaging the kidney |
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What is the major use of one-carbon groups?
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Purine synthesis
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For most methylation reactions, the methyl group on N5-methyl-THF is not sufficiently reactive. What is the more reactive methyl-group donor?
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S-adenosyl-methionine (SAM)
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In general terms, how is SAM made?
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N5-methyl-THF adds a 1-carbon group to homocysteine to make methionine which is converted to SAM.
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What is the enzyme that converts N5-methyl-THF + Homocysteine to Methionine + THF? What is the cofactor?
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Methionine Synthase
Methylcobalmin |
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Half of the Homocysteine is converted to Methionine. What happens to the other half?
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Converted to Cystathionine
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What is the function of cystathionine?
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Needed for proper brain function (mechanism unknown)
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What is the dietary source of cobalamin?
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meats and dairy products
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What does cobalamin first bind to in the stomach?
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Haptocorrin
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Where is haptocorrin secreted from?
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Salivary glands and gastric mucosa
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What happens to the cobalamin-haptocorrin complex once in the duodenum?
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They dissociate and cobalamin binds intrinsic factor?
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Where is instrinsic factor secrted from?
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Parietal cells in the stomach
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What occurs once the cobalamin-instrinsic factor complex enters the ileum?
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It is taken up by intestinal cells via cubam.
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What happens to the cobalamin-instrisic factor once inside the ileum enterocyte?
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They dissociate, cobalamin enters a secretory vesicle, binds transcobalamin II and enters the blood stream
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Once taken up by peripheral cells, what two enzymes does cobalamin act as a cofactor for?
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Methionine Synthase
Methylmalonyl-CoA mutase |
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What is pernicious anemia?
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Insufficient secretion of instrinsic factor leads to inadequate cobalamin uptake
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What chemical is coupled with decreased cobalamin uptake?
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Nitrous Oxide (laughing gas)
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SAM is used in the biosynthesis of these three things
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Creatine, Phopholipids, EpinephrineS
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SAM can also be used to methylate these two things
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Nucleic Acids and Proteins
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What is the function of creatine?
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Gets phosphorylated by ATP to form Phosphocreatine. This then transports energy to myosin filaments. Creatinine is the waste product.
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What is Leucovorin?
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=Folinic Acid = N5-formyl-THF
Can be converted to N5/N10-methenyl-THF. |
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Why is Leucovorin useful?
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N5/N10-methenyl-THF is part of the general folate pool. Used following antifolate chemodrugs.
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