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33 Cards in this Set

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