BIOCHEMICAL ASPECTS OF VITAMIN B12 DEFICIENCYBy Stephanie Houston

WHAT IS VITAMIN B12?• 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 LiverCobalamin molecular formula = C63H88CoN14o14P 

THE MAIN VARIETIES OF B12Cyanocobalamin –

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)

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

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 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

Ramsey, D. (2011). The farmacy. Retrieved from 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

REFERENCESSlide #3

Jaouen, G., ed. (2006). Bioorganometallics: Biomolecules, Labeling, Medicine. Weinheim: Wiley-VCH. ISBN 3-527-30990-X.

PubChem. (2014). cyanocobalamin - substance summary. Retrieved from 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

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/Cobalamin

Slide 5

The George Mateljan Foundation. (2014). Vitamin b12 cobalamin. Retrieved from 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

Slide #6

Greg, MD, M. (2013, March 3). Optimum vegetarian. Retrieved from 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

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-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

Slide 9University of Maryland Medical Center (2013, June 24).vitamin b12 (cobalamin). Retrieved from 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