HNF 462 1st Edition Lecture 8Outline of Last LectureI. Food Sources and DigestionII. AbsorptionIII. TransportIV. Functionsa. Coenzymeb. Gene Expressionc. Protein ModificationV. ExcretionVI. Deficiency Outline of Current LectureI. StructureII. SourcesIII. DigestionIV. AbsorptionV. Transport and StorageVI. BioavailabilityVII. ExcretionVIII. Conversions and Functionsa. DNA synthesisb. Homocysteine conversionc. Metabolism of Amino acidsThese notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.IX. Importancea. Dividing Cellsb. Hyperhomocystenemiac. Neural Tube DefectsX. MeasurementCurrent Lecture: Folate 1. Structure: folate contains 3 parts to structure (pteridine, PABA, and glutamic acid)a. When reduced, 2 double bonds (of carbons 5-8) are converted to single bonds bythe addition of hydrogenb. Nitrogens at positions 5 and 10 can be attached to 1-carbon unitsc. Because of different arrangements, there are more than 100 forms that naturally occur in food2. Sourcesa. Food (ex. green veggies, legumes, liver): methylated and reduced forms with various numbers of glutamates—in the form of folateb. Supplements: in the form of folic acid—oxidized form, only one glutamate; most easily absorbed form3. Digestion: digestion is needed to convert to monoglutamate forma. Achieved by zinc-dependent enzyme called FGCP4. Absorptiona. Into the Intestine by proton-coupled folate transporter called PCFTi. Into intestinal cells and is converted to DHF and TFHb. Into portal blood as reduced/methylated form = 5-methyl THFc. Into non-intestinal cells by reduced folate carrier (RFC), PCFT, or folalte receptorsi. Once in cells, 4-8 additional glutamates added to trap in cells5. Transport and Storagea. Transported in blood as 3 forms (THF, 5-methyl THF, and 10-formyl THF) and monoglutamate forms onlyb. ~50% stored in the liver as polyglutamate forms6. Bioavailabilitya. Supplements/Fortified Foods > Natural Food because no digestion is needed withfolic acidb. Inhibitors: ethanol, zinc deficiency7. Excretiona. Mainly through urine in intact and metabolized formsb. Some through feces because liver excretes folate with bile, but the reabsorption rate is high8. Conversions and Functionsa. Coenzyme in reactions (acceptor/donor of 1-carbon unit)b. Folate is reduced to DHF THF, and from there can take many pathwaysc. THF 5,10-methenyl THF 5,10-methylene THFi. 5,10-methylene THF important in creating pyrimidines for DNA synthesis and for metabolism of some amino acids (Ex. serine glycine by transfer of one carbon)d. 5,10-methylene THF 5-methyl THFi. 5-methyl THF important in controlling homocysteine levels in blood through conversion of homocysteine to methionine)e. 5,10-methenyl THF 10-formyl acid THFi. 10-formyl acid THF important in purine synthesis9. Importancea. Dividing Cells: Need to efficiently make DNA so cells can divide rapidlyi. If DNA is not made fast enough, magaloblastic macrocytic anemia could occurii. Methotrexate: inhibitor of reductase so DHF cannot be converted to THF and cancer cells will grow at a slower rateb. Hyperhomocystenemiai. Mutant enzyme that converts 5,10-methylene THF 5-methyl THF = increased levels of homocysteine = increased risk of coronary heart diseaseii. People with this condition need to increase intake of folate to compensatec. Neural Tube Defects: folate is critical for proper closing of neural tubes in early pregnancy or else Spina Bifida/Anencephaly could occur10. Measurementa. Directly in blood, serum, or plasmab. FIGLU Excretion: folate converts FIGLU glutamate. If a person is folate deficient, then they will excrete more FIGLU in urinec. Thymidylate Synthetase Activity: decreased activity could signal folate or B12
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