1. BIOCHEMICAL ASPECTS OF VITAMIN B12 DEFICIENCY By Stephanie Houston

2. WHAT IS VITAMIN B 12 ? A collection of cobalt + corrin ring molecules that perform similar functions in the body Essential water soluble biomolecule Organometallic compound containing a cobalt ion, which colors the molecule red Aids in the development of RBC’s, DNA production, myelin sheath fatty acid synthesis, and amino acid metabolism Exists in a variety of forms called cobalamins Manufactured by the microorganisms inside the stomachs of cows and sheep Stored in the human Liver Cobalamin molecular formula = C63H88CoN14o14P

3. THE MAIN VARIETIES OF B12 Cyanocobalamin – used in vitamin supplements Methylcobalamin & 5-deoxyadenosylcobalamin – used in cellular metabolism

4. CORE OF THE MOLECULE Corrin Ring The central metal ion is cobalt Four of the six coordination sites are fulfilled by the Corrin ring Dimethylbenzimidazole provides the fifth site The sixth site is variable Dark red color because of the cobalt-corrin complex

5. SOURCE AND STORAGE OF VITAMIN B12 Not synthesized by plants and animals; humans do not manufacture B12 and must obtain it though dietary sources Found in bacteria of animals in the intestines Best sources: Organs Beef, Chicken, and Pork Fish Dairy products Seafood Nutritional Yeast Fortified cereals and soy products Liver stores B12 with enough for a 3 year supply RDA: Children 0.2mcg/d, Adults 1mcg/d, Preg or lactating adult 1.5mcg/d,

6. ENZYMATIC & BIOLOGICAL IMPORTANCE Vitamin B12 Folate and the relationship of Hyperhomocyctinemia (skip to 47:00 minutes) http://www.youtube.com/watch?v=q7KeRwdIH04 The cofactor adenosylcobalamin is required for the conversion of methylmalonyl coenzyme A to succinyl coenzyme A Methylcobalamin is needed to convert 5-methyltetrahydrofolate to tetrahydrofolate and is necessary for DNA and red blood cell production Formation of collagen

7. DEFICIENCY Clinical deficiency is severe, exhibiting hematologic and/or neurologic signs and symptoms, cobalamin levels < 200 pg/mL, and levels for Hcy and methylmalonic acid (MMA) that are usually elevated. Subclinical deficiency is the more common type & includes absent signs and symptoms, with only subtle changes in neurologic processes seen in some; low to low-normal cobalamin levels (200–350 pg/mL); and at least one metabolic abnormality (elevated homocysteine or elevated methylmalonic acid), usually mild. Depleting stores can take 3-5 years Deficiency is likely to happen in adults >65 years old, vegans, people with pernicious anemia, or who have had gastric surgery, gastritis, Crohn’s disease, HIV, or Celiac disease Dietary B12 is absorbed in the ileum of the small intestine and requires the presence of R protein (haptocorrin from saliva), gastric acid, pepsin, and intrinsic factor

8. BIOMECHANICAL DISORDERS Pernicious Anemia- decreased ability of IF to bind to B12, treated with injections B12 malabsorption- caused by decreased stomach acid production and a resulting overgrowth of bacteria, treated with supplement B12 that is not bound to food B12 supplements can interact with certain medications

9. Methylation: the relationship of Folate and B12:

10. REFERENCES Slide #2 Image Encyclopedia Britannica, Inc. (2014). Vitamin b12. Retrieved from http://www.britannica.com/EBchecked/topic/631051/vitamin-B12 http://www.britannica.com/EBchecked/topic/631051/vitamin-B12 UC Davis. (2014). Cobalamin 1. Retrieved from http://chemwiki.ucdavis.edu/Biological_Chemistry/Vitamins,_Cofactors_and _Coenzymes/Cobalamin/Cobalamin_1 http://chemwiki.ucdavis.edu/Biological_Chemistry/Vitamins,_Cofactors_and _Coenzymes/Cobalamin/Cobalamin_1 Ramsey, D. (2011). The farmacy. Retrieved from http://drewramseymd.com/index.php/resources/farmacy http://drewramseymd.com/index.php/resources/farmacy McKinley Health Center. (2008). Vitamin b12: What vegans need to know. Retrieved from http://www.mckinley.illinois.edu/handouts/vitamin_b12/vitamin_b12.htm

11. REFERENCES Slide #3 Jaouen, G., ed. (2006). Bioorganometallics: Biomolecules, Labeling, Medicine. Weinheim: Wiley- VCH. ISBN 3-527-30990-X.Bioorganometallics: Biomolecules, Labeling, MedicineISBN3-527-30990-X PubChem. (2014). cyanocobalamin - substance summary. Retrieved from http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=5771 http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=5771 Thorne Research Inc. (2013). Methylcobalamin. Retrieved from http://www.thorne.com/Products/Mood-Sleep-Support/Sleep_Management/prd~B125.jsp Slide #4 Encyclopedia Britannica, Inc. (2014). Pyrrole. Retrieved from http://www.britannica.com/EBchecked/topic/485130/pyrrole http://www.britannica.com/EBchecked/topic/485130/pyrrole SH 328, Week 4, PowerPoint 4.7 Vitamins and Minerals UC Davis. (2014). Cobalamin. Retrieved from http://chemwiki.ucdavis.edu/Biological_Chemistry/Vitamins,_Cofactors_and_Coenzymes/Cob alamin Slide 5 The George Mateljan Foundation. (2014). Vitamin b12 cobalamin. Retrieved from http://www.whfoods.com/genpage.php?tname=nutrient&dbid=107 http://www.whfoods.com/genpage.php?tname=nutrient&dbid=107 Charest, RD, M.Sc, A. (2014). Milk: An essential source of vitamin b12. Retrieved from http://www.dairynutrition.ca/nutrients-in-milk-products/other-nutrients/milk-an-essential-source- of-vitamin-b12http://www.vrg.org/nutshell/vegan.htm#vitb12

12. Slide #6 Greg, MD, M. (2013, March 3). Optimum vegetarian. Retrieved from http://www.youtube.com/watch?v=q7KeRwdIH04 http://www.youtube.com/watch?v=q7KeRwdIH04 SH 328, Week 4, PowerPoint 4.7 Vitamins and Minerals Slide 7 U.S. National Library of Medicine. (2013, Oct. 31). Intrinsic factor. Retrieved from http://www.nlm.nih.gov/medlineplus/ency/article/002381.htm http://www.nlm.nih.gov/medlineplus/ency/article/002381.htm Slide # 7 & 8 CDC. (2009, June 29). Vitamin b12 deficiency. Retrieved from http://www.cdc.gov/ncbddd/b12/history.htmlSH 328, Week 4, ppt. 4.7 Slide 8 Ehrlich, N.M.D., S. D. (2007, Sept. 06). Possible interactions with: Vitamin b12 (cobalamin). Retrieved from http://umm.edu/health/medical/altmed/supplement-interaction/possible- interactions-with-vitamin-b12-cobalaminhttp://umm.edu/health/medical/altmed/supplement-interaction/possible- interactions-with-vitamin-b12-cobalamin The Johns Hopkins University. (2013). Anemia of b12 deficiency (pernicious anemia). Retrieved from http://www.hopkinsmedicine.org/healthlibrary/conditions/hematology_and_blood_disorders /anemia_of_b12_deficiency_pernicious_anemia_85,P00080/ REFERENCES

13. Slide 9 University of Maryland Medical Center (2013, June 24).vitamin b12 (cobalamin). Retrieved from http://umm.edu/health/medical/altmed/supplement/vitamin-b12- cobalamin http://umm.edu/health/medical/altmed/supplement/vitamin-b12- cobalamin Slide 10 Higdon, Ph.D, J. (2003, March). Vitamin b12. Retrieved from http://lpi.oregonstate.edu/infocenter/vitamins/vitaminB12/index.html REFERENCES