BIOCHEMICAL ASPECTS OF VITAMIN B12 DEFICIENCY By Stephanie Houston

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

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

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

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,

ENZYMATIC & BIOLOGICAL IMPORTANCE Vitamin B12 Folate and the relationship of Hyperhomocyctinemia (skip to 47:00 minutes) 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

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

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

Methylation: the relationship of Folate and B12:

REFERENCES Slide #2 Image Encyclopedia Britannica, Inc. (2014). Vitamin b12. Retrieved from UC Davis. (2014). Cobalamin 1. Retrieved from _Coenzymes/Cobalamin/Cobalamin_1 _Coenzymes/Cobalamin/Cobalamin_1 Ramsey, D. (2011). The farmacy. Retrieved from McKinley Health Center. (2008). Vitamin b12: What vegans need to know. Retrieved from

REFERENCES Slide #3 Jaouen, G., ed. (2006). Bioorganometallics: Biomolecules, Labeling, Medicine. Weinheim: Wiley- VCH. ISBN X.Bioorganometallics: Biomolecules, Labeling, MedicineISBN X PubChem. (2014). cyanocobalamin - substance summary. Retrieved from Thorne Research Inc. (2013). Methylcobalamin. Retrieved from Slide #4 Encyclopedia Britannica, Inc. (2014). Pyrrole. Retrieved from SH 328, Week 4, PowerPoint 4.7 Vitamins and Minerals UC Davis. (2014). Cobalamin. Retrieved from alamin Slide 5 The George Mateljan Foundation. (2014). Vitamin b12 cobalamin. Retrieved from Charest, RD, M.Sc, A. (2014). Milk: An essential source of vitamin b12. Retrieved from of-vitamin-b12http://

Slide #6 Greg, MD, M. (2013, March 3). Optimum vegetarian. Retrieved from 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 Slide # 7 & 8 CDC. (2009, June 29). Vitamin b12 deficiency. Retrieved from 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 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 /anemia_of_b12_deficiency_pernicious_anemia_85,P00080/ REFERENCES

Slide 9 University of Maryland Medical Center (2013, June 24).vitamin b12 (cobalamin). Retrieved from cobalamin cobalamin Slide 10 Higdon, Ph.D, J. (2003, March). Vitamin b12. Retrieved from REFERENCES