B12 Cobalamin Flashcards
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Which B-vitamin plays a role in myelin maintenance?
B12
neurological symptoms of B12 deficieny are caused by demyelination of nerves
What B-vitamin deficiencies are associated with megaloblastic anemia?
Folate and B12
Match the micro nutrients to their biological function
B6
Folic Acid
B12
Purine and pyrimidine synthesis
Transamination
conversion of methymalonyl CoA to a Kreb’s cycle intermediate
B6 - transaminiation
Folate - purine and pyrimidine synthesis
B12 - conversion of methymalonyl CoA to a Kreb’s cycle intermediate (succinyl CoA)
Vitamin B12 is stored mainly in what part of the body?
liver
unlike other water soluble vitamins B12 can be stored and retained in the body for long periods of time. It is stored mainly (~50%) in the liver.
Why is intrinsic factor important?
it is required for the absorption of vitamin B12
After release from R protein b12 binds to intrinsic factor
What is the source of all vitamin B12 synthesis in nature?
microorganisms
the only dietary sources are animal foods which have derived their cobalamins from microorganisms.
Which mineral is a component of vitamin B12?
cobalt
cobalamin
What is the primary cause of B12 deficiency seen in the US?
inadequate absorption
due to pernicious anemia or atrophic gastritis or gastrectomy
NOT inadequate dietary intake
What are the most reliable signs of a B12 deficiency?
Manifestations of vitamin B12 deficiency
- serum vit B12 concentrations diminish
- cell concentrations of B12 are depleted
- methylmalonic acid and homocysteine concentrations increase
- megaloblastic macrocytic anemai develops
symptoms skin pallor fatigue shortness of breath palpitations insomnia tingling and numbness in extremeties abnormal gait loss of concentration memory loss disorentation swelling of myelinated fibers dementia
What vitamin deficiency can result in a tissue deficiency of active folate?
vitamin B12
this is known as the methyl-folate trap
without B12 the methyl group from 5-methyl THF can’t be removed and thus is trapped
A deficiency of either B12 or folate can be determined by what laboratory test?
deoxyuridine suppression test
Which B vitamin can mask a B12 deficiency?
folate
Which vitamin may become deficient due to reduced absorption when protein digestion is impaired?
B12
B12 attached to R protein must be able to be separated so can attache to IF for absorption
Name good food sources of vitamins B12
animal products
meat and meat products poultry fish shelfish (esp clams and oysters) eggs
Name all of the B vitamins that are involved in homocysteine metabolism.
folate (as THF)
B12
B6 (cystathionine synthase is PLP dependent)
betaine
(also called trimethyl glycine. Folic acid supplementation appears to increase betaine concentrations and betaine appears to be able to reduce plasma homocysteine concentrations in those with elevated blood levels
List the options for treatment of pernicious anemia
monthly intramuscular injection
oral ingestion of pharmacologic amounts (2 mg) of the vitamin
B12 nasal sprays
Which groups of people are vitamin B12 supplements likely to be necessary in order to prevent B12 deficiency?
people over 50 years of age
people with atrophic gastritis
people with gastric bypass
vegans
people using gastric acid reducing drugs long term
people with achlorhydria (diminished hydrochloric acid release or excessive quantities of gastric acid
From the Teach-in presentations and Week 8 Discussion Wrap-Ups, list some therapeutic uses of one or a combination of B-vitamins.
diabetes osteoarthritis schizophrenia autism hyperhomocysteinemia depression cognitive decline migrane headaches
from Gaby Book folate atherosclerosis hyperhomocysteinemia stroke psoriasis dermatitis vitiligo ataxia migraine peripheral neuropathy restless leg syndrome autism dementia/cognitive decline depression
What are the forms of B12?
cyanocobalamin - found in some supplements
hydroxocobalamin -
adenosylcobalamin - coenzyme form in the body
methylcobalamin - coenzyme form in the body
What are good food sources of B12?
Animal products
which derive cobalamins from microorganisms
meat
eggs
shellfish (clams 84 mcg, oysters 30 mcg / 100g)
contain primarily adenosyl- and hydroxocobalamin forms
milk and diary products contain less but may have a more bioavailable form of B12 (methyl- and hydroxocobalamin)
What are the steps in digestion and absorption of B12?
- B12 must be released from the proteins it is attached to in food
- B12 binds to an R protein found in saliva and gastric juice. R proteins are thought to protect B12 from use by bacteria.
- In alkaline small intestine, R protein is hydrolyzed and B12 is released and attaches to Intrinsic Factor (produced by gastric parietal cells)
- B12-IF travels to ileum where it interacts with a protein receptor, cublin or IF receptor, and is absorbed by endocytosis.
What protein transports B12 in portal blood?
transcobalamin II
What is the cause of pernicious anemia?
Destruction of the gastric parietal cells which produce intrinsic factor by an autoimmune response.
Lack of intrinsic factor results in malabsorption of B12.
What factors interfere with B12 absorption by causing a more acidic pH in the small intestine?
- pancreatic insufficiency (lack of bicarbonate in pancreatic fluid)
- Zollinger-Ellison syndrome which increases output of gastric acid
In a acidic environment, B12 will preferentially stay attached to R protein instead of intrinsic factor.
Can pernicious anemia be treated with oral B12?
Yes. About 1% to 3% of pharmacological doses (1000 to 2000 mcg) can be absorbed by passive diffusion.
Can B12 be recycled in the body?
Yes. B12 can be excreted in bile. In the small intestine it can bind to IF for reabsoprtion.
This recycling provides about 3 to 8 mcg of B12 per day.
What is unique about B12 as a water soluble vitamin?
It can be stored in the body (liver) for long periods of time.
About 2 to 4 mg of the vitamin is stored in the body, mainly in the liver. (The RDA is 2.4 mcg per day)
Consequently, deficiency may take 3 to 5 years to develop.
What are the two enzymatic reactions requiring B12?
- The conversion of homocysteine to methionine requires B12 as a cofactor for methionine synthase which takes a methyl group from 5-methyl THF. (Lack of B12 results in the methyl-folate trap or functional folate deficiency).
- The conversion of methylmalonyl-CoA to succinyl-CoA. Methylmalonyl-CoA results from the metabolism of propionyl-CoA. Propionyl-CoA results from the oxidation of methionine, isoleucine, threonine and odd chain fatty acids. Succinyl-CoA is an intermediary in the CAC.
The conversion of methylmalonyl-CoA to succinyl-CoA also requires ATP, Mg, and biotin.
What deficiency disease is associated with B12 deficiency and how is it caused?
Megaloblastic macrocytic anemia.
B12 deficiency leads to a functional deficiency of folate due to the folate trap. (Folate trapped in the 5-methyl form without B12 and can not be used by cell for DNA synthesis).
Can folate alleviate the symptoms of B12 deficiency?
Folate can hide the effect of B12 deficiency on red blood cells; however, folate can not stop the neurological damage that is caused by B12 deficiency.
What are the neurologic symptoms of B12 deficiency?
neurological symptoms occur in 75 to 90% of people with B12 deficiency.
- numbness in extremities
- abnormal gait
- increased loss of coordination
- loss of proprioreception
- loss of vibration sense or tough in ankles and toes
- swelling of myelinated fibers and demylination
- irritability
- memory loss
- disorientation
- psychosis
How can B12 deficiency be produced?
Inadequate intake
- vegan diets (especially in infants or young children with low B12 stores)
Malabsorption which may be caused by
- Pernicious anemia (autoimmune condition that destroys parietal cells which produce IF)
- Food cobalamin malabsorption (lack of HCl due to use of PPIs or H2 blockers or hypochlorhydria due to other causes. B12 not released from food so can’t be absorbed.)
- Atrophic gastritis (common in elderly, results in inflammation and loss of gastric cells and diminishes HCl production).
- Zollinger-Ellison syndrome (high amounts of gastric acid result in low pH in small intestine and B12 stays attached to R protein)
- Impaired intestinal function - Celiac disease or Crohn’s disease
- Parasitic infections (parasites like tapeworms compete for B12)
- Impaired pancreatic exocrine function (lack of digestive juice with bicarbonate lowers pH of digestive tract and impairs release of B12 from R protein.
What tests are used to assess B12 deficiency?
- Serum B12 - reflects both intake and status. But serum levels can be maintained at the expense of tissue levels of B12.
- Methylmalonyl CoA. Serum and urinary concentrations increase when B12 insufficient.
- New breath test has been developed. Labeled CO2 levels in the breath are measured after intake of labeled proprionate.
- Deoxyuridine suppression test.
- Shilling Test (old test for pernicious anemia)
- Antibodies to intrinsic factor or parietal cells is now used as indicator of pernicious anemia.
