BIOCHEMICAL ASPECTS OF VITAMIN B12 DEFICIENCY
By Vitaminquick
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 Liver Cobalamin molecular formula = C63H88CoN14o14P
THE MAIN VARIETIES OF B12 Cyanocobalamin –
Methylcobalamin &
used in vitamin supplements
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 • 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:
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