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Eric Niederhoffer SIU-SOM

A 38-year-old woman is brought to the physician because of frequent falls, increasing confusion, and incontinence. A 29-year-old woman is brought to the physician because of thought abnormalities. What is the role of vitamins in metabolic pathways?. Eric Niederhoffer SIU-SOM.

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Eric Niederhoffer SIU-SOM

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  1. A 38-year-old woman is brought to the physician because of frequent falls, increasing confusion, and incontinence A 29-year-old woman is brought to the physician because of thought abnormalities What is the role of vitamins in metabolic pathways? Eric Niederhoffer SIU-SOM

  2. Names and roles for vitamins and vitamin-like substances Deficiencies and sources for vitamins and vitamin-like substances Vitamin A transport Role in pathways (glycolysis, glycogenolysis, PPP) Role in pathways (TCA cycle, gluconeogenesis) Important neurologic amino acids Neurotransmitter pathway Tetrahydrofolate conversions Tetrahydrofolate examples B12 pathways Megaloblasticanemia Schilling test Vitamins in Neuromuscular Metabolism

  3. Names and Roles for Vitamins and Vitamin-like Substances

  4. Deficiencies and Sources for Vitamins and Vitamin-like Substances

  5. β-carotene (plants) retinyl ester (animals) retinal retinol retinyl ester (small intestine) Liver storage retinol Target tissue Vitamin A Transport PA RBP

  6. Glycogenolysis Glycolysis Glc Glycogen G6P G1P R5P PPP G3P 1,3BPG Pyr Ala Lactate Role in Pathways(glycolysis, glycogenolysis, PPP) PP a vit B6 G6PDH/6PGDH vit B3 TK vit B1 G3PDH vit B3 LDH vit B3 ALT vit B6

  7. Pyr Acetyl-CoA Asp OA BCAA Ile, Leu, Val Mal TCA cycle IC Fum Glu BCKA αKG Suc SCoA Role in Pathways(TCA cycle, gluconeogenesis) PDH vit B1,B2,B3, B5, lipoic acid PC vit B7 AST vit B6 MDH vit B3 ICDH vit B3 SDH vit B2 ALT vit B6 αKGDH vit B1,B2,B3, B5, lipoic acid BCKADH vit B1,B2,B3, B5, lipoic acid

  8. PLP (vit B6) deCO2ase PLP (vit B6) deCO2ase Important Neurologic Amino acids Glutamate γ-Aminobutyrate Phenylalanine BH4 PheOHase Phenylketonuria (PKU) Dopamine Norepinephrine Epinephrine PLP (vit B6) Tyrosine deCO2ase Tryptophan Serotonin

  9. PLP (vit B6) AAA deCO2ase BH4, O2 Tyr OHase Menkes disease DβOHase Vit C, O2 PNMT Epinephrine SAHC SAM Dopamine Pathway Homovanillic acid (HVA) Degradation Tyrosine DOPA Dopamine Norepinephrine Metanephrine Normetanephrine Degradation (MAO/COMT) Vanillylmandelic acid (VMA) 3-Methoxy-4-hydroxymandelic acid (HMMA)

  10. PLP (vit B6) AAA deCO2ase BH4, O2 TrpOHase Serotonin Pathway Melatonin Serotonin (5-HT) Tryptophan 5HTRP 5-Hydroxyindoleacetic acid (5-HIAA) 3-Hydroxykynurenine Xanthurenate PLP (vit B6) Kynureninase Cytosolic/mitochondrial degradation pathway

  11. DHF reductase (dUMP to dTMP to DNA) DHF reductase (HC to Met) (His to Glu) (Ser to Gly) N10-formyl-THF N5-formimino-THF N5,N10-methenyl-THF N5,N10-methylene-THF N5-methyl-THF Tetrahydrofolate Conversions Folate DHF THF Most oxidized Most reduced

  12. NAD+ NADH + H+ N5,N10-MLTHF N5,N10-MLTHF THF THF PLP Ser Gly CO2 + NH4+ serine hydroxymethyl transferase glycine synthase THF N5-FTHF His Glu glutamate formimino transferase dUMP dTMP thymidylate synthase N5,N10-MLTHF 7,8-DHF THF DHF reductase A series of reductases Tetrahydrofolate examples

  13. Odd-chain FA oxidation/ AA metabolism MMCoAmutase TCA cycle Vit B12 (H exchange) Met Ad transferase THF R Met synthase A variety of MTs Vit B12 R-CH3 N5MTHF hydrolase Purines, dTMP B12Pathways L-MMCoA SCoA Methyl transfers (1C metabolism) ATP + Met S-AdMet HC S-AdHC

  14. Megaloblastic Anemia This hypersegmented neutrophil is present along with macro-ovalocytes in a case of pernicious anemia. Compare the size of the RBC's to the lymphocyte at the lower left center. Such anemias can be due to B9 (folate) or to B12 (cobalamin) deficiency. http://library.med.utah.edu/WebPath/HEMEHTML/HEME083.html

  15. Schilling Test 58Co-B12 + I.M. B12 IF present IF absent 58Co-B12-IF 58Co-B12 GI absorption No GI absorption Liver storage (~80%) Plasma protein binding (~5%) Fecal excretion Excreted in urine (~15%) Low 58Co-B12 in urine

  16. What are the different names for vitamins A, B1, B2, B3, B5, B6, C, and B12? Which pathway depends on vitamin A and how is it transported? Which pathways and enzymes depend on vitamin B1, B2, B3, B6, B9, and B12? Which pathway and enzyme depends on p-aminobenzoicacid, choline, lipoic acid, and tetrahydrobiopterin? What are some clinical features and tests of vitamin deficiencies? Review Questions

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