1 / 22

Folic Acid

Folic Acid. FIGURE 1: Chemical Structure of Folic Acid [8]. By: Linda Kim Andrew Liu Milton Reisis. PHM 226, Example Instructor: Dr. Jeffrey Henderson. WHAT IS FOLIC ACID?. Folic acid = pteroylmonoglutamic acid, folacin, vitamin Bc, vitamin B9 and Lactobacillus casei factor [8].

liam
Download Presentation

Folic Acid

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Folic Acid FIGURE 1: Chemical Structure of Folic Acid [8] By: Linda Kim Andrew Liu Milton Reisis PHM 226, Example Instructor: Dr. Jeffrey Henderson

  2. WHAT IS FOLIC ACID? • Folic acid = pteroylmonoglutamic acid, folacin, vitamin Bc, vitamin B9 and Lactobacillus casei factor [8]. • Folic acid is a water-soluble B-vitamin [8] • MW = 441kDa • Must be ingested in diet (cannot be synthesized by body)

  3. WHY IS FOLIC ACID NEEDED? • Formation of the coenzyme referred to as tetrahydrofolate (THF) [1] • Essential for creating heme, the iron containing substance in haemoglobin [1] • Proper formation of the brain, spinal cord, and nerve cells in the embryo.  Closure of the neural tube in the fetus cannot be completed without it (Northrup H, 2000).  • Essential for synthesis of serine, methionine, ATP, GTP, thymidylate

  4. ABSORPTION • Natural food source (polyglutamate): conjugase in the small intestine’s lumen converts polyglutamates (low absorption) to monoglutamates for absorption [4] • Monoglutamate is readily absorbed from the gut via energy-dependent, carrier-mediated mechanisms, involving membrane-associated folate-binding proteins [4]

  5. DISTRIBUTION • Tetrahydrofolate (THF) and its derivatives distribute to all body tissues [4] • N5-methyl-THF is the major storage form of folate in the body (i.e. ~50% in liver) [4] • N5-methyl-THF is highly bound to albumin [4]

  6. METABOLISM • Folate reduced to dihydrofolate (DHF) and then to tetrahydrofolate (THF) within cells, by dihydrofolate reductase (DHFR) and NADH [7] • Addition of glutamate residues to THF in the cell keep it within the cell to form its active coenzyme in one-carbon metabolism reactions [7] • 5-methyl-THF is formed by the reduction of N5, N10-methylene-FH4 by N5, N10-methylene-THF reductase [7] • Normally, folate is excreted in the urine; folate is also excreted in the bile, if not reabsorbed [4]

  7. TABLE 1: One-carbon pool: Sources and Recipients of Carbon [7]

  8. HOW DOES FOLIC ACID WORK? • Folic acid is converted to its active coenzyme form, THF, which behaves as a donor or receiver of a one carbon entity in different oxidation states (formyl, methylene, or methyl)

  9. FIGURE 2: FOLATE MECHANISM OF ACTION [9]

  10. FIGURE 3: MECHANISM OF ACTION – EXAMPLE [9]

  11. FIGURE 4: MECHANISM OF ACTION – EXAMPLE [2]

  12. Sources of Folic Acid • Cereals (100-400 mcg), dark green vegetables (120-160 mcg), citrus fruits (50-100 mcg) [10] • Folic acid may also be found in supplements and multivitamin combinations sold at pharmacies

  13. Folate Deficiency

  14. Causes of Folate Deficiency • Decreased intake (diet, malabsorption) • Increased need (pregnancy) • Also, consider decreased availability (antifolate drugs etc.)

  15. WHAT ARE NEURAL TUBE DEFECTS (NTDs)? The neural tube forms in the embryo and then closes (between the 2nd and 4th week of gestation) A neural tube defect occurs when the neural tube fails to close properly The two most common NTDs are anencephaly and spina bifida

  16. What is Spina Bifida? • Occurs when the two sides of the spine fail to close and protect the spinal cord • There are two forms of spina bifida: • Spina bifida occulta (mildest form) 2) Spina bifida manifesta which includes two types of spina bifida: meningocele and myelomeningocele

  17. What is Spina Bifida? Source: http://www.surgical-tutor.org.uk/default-home.htm?system/hnep/neural_tube.htm~right

  18. What Causes Spina Bifida? • Largely unknown • Some evidence suggests that genes may be involved. (Northrup H et al, 2000) • A high fever during pregnancy or epileptic women who have taken the drug valproic acid to control seizures may have an increased risk of having a baby with spina bifida. (Lewis DP et al, 1998)

  19. How Can NTDs be Prevented? • All women of childbearing age should receive 0.4 mg (400 micrograms) of folic acid daily prior to conception of planned or unplanned pregnancies and continue thru 1st trimester • Women with a history of NTD and should receive daily supplementation of 4 mg (4000 micrograms) of folic acid starting three months prior to conception and continuing thru the 1st trimester

  20. References [1] Adams, S.L. 2003. Biochemical Functions of Folic Acid, http://www.i2k.com/~suzanne/page25.htm, accessed January 2004. [2] Angstadt, C.N. 1997. Purine and Pyrimidine Metabolism, http://www.mcphu.edu/netbiochem/pupyr/pp.htm#Syn%20TMP, accessed January 2004. [3] Castillo, E.S. 1991. Folic Acid, http://www.inchem.org/documents/pims/pharm/folicaci.htm#PartTitle:3.%20PHYSICO-CHEMICAL%20PROPERTIES, accessed January 2004. [4] Expert Group on Vitamins and Minerals. 2002. Review of Folic Acid, http://www.foodstandards.gov.uk/multimedia/pdfs/evm0018p.pdf, accessed January 2004. [5] Fenech M. 2001. The role of folic acid and vitamin B12 in genomic stability of human cells.Mutat Res 475(1-2):57-67 [6] Larsen, H.R. 2000. Folic Acid: Don’t Be Without It!, http://vvv.com/healthnews/folic_acid.html, accessed January 2004. [7] Marks, D.B., Marks, A.D., and Smith, C.M. 1996. Basic Medical Biochemistry: A Clinical Approach., Williams and Wilkins, Maryland, pp 613-632. [8] No author. 2002. Folic Acid, http://www.chm.bris.ac.uk/webprojects2002/schnepp/folic.html, accessed January 2004. [9] No author. 2002. Main Folate Metabolism Pathways, http://www.humboldt.edu/~rap1/BiochSupp/PathwayDiagrams/FolMetPath.gif, accessed January 2004. [10] No author. 2003. CERHR: Folic Acid, http://cerhr.niehs.nih.gov/genpub/topics/folic_acid-ccae.html, accessed January 2004. [11] Wolfson, D. 2001. Pharmaceutical Drugs Deplete Folic Acid, http://www.newhope.com/nutritionsciencenews/NSN_backs/Sep_01/folic.cfm, accessed January 2004.

  21. References *For NTD section • AllRefer Health – Caring for your Well Being: http://health.allrefer.com/health/folic-acid-folate-info.html • Champel V et al. Should folic acid be given to women treated with valproic acid and/or carbamazepine? Folic acid and pregnancy in epilepsy. Rev Neurol. 1999 Mar; 155(3): 220-4. • Geisel J. Folic acid and neural tube defects in pregnancy: a review. J Perinat Neonatal Nurs. 2003 Oct-Nov; 17(4): 268-79. • Lewis DP et al. Drug and environmental factors associated with adverse pregnancy outcomes. Part I: Antiepileptic drugs, contraceptives, smoking, and folate. Ann Pharmacother. 1998 Jul-Aug; 32(7-8): 802-17. • Lewis DP et al. Drug and environmental factors associated with adverse pregnancy outcomes. Part II: Improvement with folic acid. Ann Pharmacother. 1998 Sep; 32(9): 947-61. Review. • MEDLINEplus – Spina Bifida: http://www.nlm.nih.gov/medlineplus/spinabifida.html • MEDLINEplus – Folic Acid: http://www.nlm.nih.gov/medlineplus/folicacid.html • Northrup H et al. Spina bifida and other neural tube defects. Curr Probl Pediatr. 2000 Nov-Dec; 30(10): 313-32. • Pregnancy and Nutrition - Spina Bifida and Folic Acid: http://www.bchealthguide.org/healthfiles/hfile38c.stm • Ray JG et al. Association of neural tube defects and folic acid food fortification inCanada. Lancet. 2002 Dec 21-28; 360(9350): 2047-8. • Spina Bifida Association of America – Facts about Spina Bifida: http://www.sbaa.org/html/sbaa_facts.html • Surgical-tutor.org.uk – a free online surgical resource: http://www.surgical-tutor.org.uk/default-home.htm?system/hnep/neural_tube.htm~right • The Arc – Prevention of Neural Tube Defects: http://www.thearc.org/faqs/folicqa.html • Wald NJ. Folic Acid and the Prevention of Neural-Tube Defects.N Engl J Med. 2004 Jan 8; 350(2): 101-3.

  22. References *For anemia section • Briggs, Gerald G., Freeman, Roger K., Yaffe, Sumner J. Folic Acid. A Reference Guide to Fetal and Neonatal Risk. Drugs in Pregnancy and Lactation. 5th Ed. Lippincott, Williams & Wilkins: Philadelphia, PA, USA. 1998. pp. 456- 467 • Cotran, Kumar, Collins et al. Red Cells and Bleeding Disorders. Pathologic Basis of Disease. W.B. Saunders Company: Philadelphia, PA. 1999. pp. 604-627 • Eichner, E.R. and Hillman, R.S. The evolution of anemia in alcoholic patients. Am. J. Med., 1971, 50:218-232 • Eichner, E.R. and Hillman, R.S. Effect of alcohol on serum folate level. J. Clin. Invest., 1973, 52:584-591 • Folic Acid. USP DI Vol. 1 Drug Information for the Health Care Professional. 23rd Ed. Micromedex: Colorado, USA. 2003. pp. 1376-1378 • Hillman, Robert S. Chapter 54 Hematopoietic Agents. Goodman & Gilman’s Pharmacological Basis of Therapeutics. 10th Ed. Hardman, Joel G., Limbird, Lee E., Goodman Gilman, Alfred, eds. The Mcgraw-Hill Companies, Inc.: USA. 2001. pp. 1503-1514 • Herbert, V., Tisman, G., Le-Teng-Go, and Brenner, L. The dU suppression test using 125-I-UDR to define biochemical megaloblastosis. Br. J. Haematol., 1973. 24:713-723 • Teresi, Mary E., Kailis, Stanley G., Berbatis, Constantine G. Iron Deficiency and Megaloblastic Anemias. Textbook of Therapeutics Drug and Disease Management. 6th Ed. Herfindal, Eric T., Gourley, Dick K., eds. Williams & Wilkins: Baltimore, Maryland, USA. 1996. pp. 201–220 • Tropical Sprue. The Merck Manual Second Home Edition. Merck & Co. Inc.: Whitehouse Station, NJ, USA, 2004. http://www.merck.com/mrkshared/mmanual_home2/sec09/ch125/ch125d.jsp

More Related