Vitamin B12 Flashcards
What are the two metabolically active forms of vitamin B12? Which enzymes and pathways do they function?
Methylcobalamin (Folate cycle)
Enzyme: methionine synthase
Adenosylcobalamin (AA metabolism)
Enzyme: methylmalonyl-CoA mutase
Outline the key steps of how vitamin B12 is absorbed?
- B12 is consumed in the diet (primarily animal sources)
- B12 is bound to R-protein (protects from being digested in the stomach
- R-protein is separated from B12 via protease (synthesized in the stomach)
- B12 is then bound to Intrinsic Factor (IF) (released by gastric parietal cells) in the small intestine (SI)
- Cubam binds IF-B12 and the complex is internalized into endosomes
- Endosomes fuse into lysosomes, where IF is degraded (by low lysosomal pH) and B12 is transported into the cytosol
- B12 is transported into the bloodstream and then
- absorption occurs in the terminal ileum
What are the biomarkers used to assess B12 status?
MMA (methylmalonic acid) - most specific to B12
Homocysteine - specific to folate and B12 levels
Plasma vitamin B12 (most common biomarker)
How is vitamin B12 deficiency defined?
deficiency is defined as having signs/symptoms of anemia such as fatigue, weakness, neurological symptoms, etc.
Biomarkers of elevated MMA and homocysteine can also be indicators of a B12 deficiency (usually from a lack of intake of B 12-containing foods)
What is pernicious anemia (PA)?
What is the main cause of PA?
Pernicious anemia occurs as a result of the destruction of gastric parietal cells therefore resulting in impaired function of intrinsic factor secretion to an interruption of the process of vitamin B12.
PA is caused by an inability to complete the absorption process of vitamin B12 while still eating adequate B12-containing foods.
What are the commons forms of treatment for vitamin B12 deficiency?
intramuscular injections (IM) oral supplementation
What are some advantages to treating deficiency with IM vs oral?
- much higher absorption with IM vs oral supplementation
- if a patient needs rapid replenishment, IM is the primary treatment method
- IM injections should be given to patients that are symptomatic
- IM should be used over oral if the patient is non-compliant
- oral should be recommended for convenience/cheaper - some patients may find it difficult to go to the doctor’s office frequently enough to get the injections
What are some of the common supplemental forms of B12?
cyanocobalamin
methylcobalamin
hydroxocobalamin
coenzyme B12
What type of anemia occurs with vitamin B12 deficiency?
macrocytic anemia (megaloblastic)
**can be caused by either folate and/or B12 deficiency
What population is at risk for vitamin B12 deficiency?
- strict vegans/vegetarians
- elderly population
- GI disorders
- GI surgery
What are the common signs/symptoms of vitamin B12 deficiency?
fatigue weakness constipation loss of appetite weight loss numbness and tingling in hands/feet difficulty maintaining balance depression confusion dementia poor memory soreness of mouth/tongue
What are some common dietary food sources of vitamin B12 for vegans?
nutritional yeast fortified plant milk tempeh fortified breakfast cereals algae/seaweed mushrooms
What autoimmune disorders are associated with pernicious anemia (PA)?
thyroid disease
diabetes mellitus
vitiligo - loss of skin pigmentation
What is SCCD? How is it related to vitamin B12?
SCCD = subclinical cobalamin deficiency
SCCD is usually shown by biomarkers of B12 deficiency, such as MMA and homocysteine concentrations
SCCD is characterized by B12 depletion as evidenced by biochemical indications of deficiency (from dietary deficiency) rather than anemia or clinical symptoms such as neuropathy
How is dietary B12 deficiency (e.g. veganism) different from pernicious anemia?
Dietary B12 deficiency - this occurs from a lack of dietary intake of foods that contain B12 (lack of dietary intake of B12, there is no ability to absorb/store it in the body, resulting in deficiency unless supplemented properly)
Pernicious Anemia (PA) - a form of B12 deficiency that occurs after adequate dietary intake of vitamin B12 but the process of absorption is disrupted due to the impairment of intrinsic factor secretion because of a result of the destruction of gastric parietal cells. Impaired IF, IF is no longer able to bind to vitamin B12 that is ingested in the diet, and therefore the absorption process is terminated (B12 is digested in the stomach)
