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Vitamin B12
By:Zahra Mahboob
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• Introduction
• Structure
• Synthesis
• Sources
• Absorbtion
• Function
• Deficiencies
• Treatment
• Vitamin B12 and Cancer
Outline…
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Introductiona water-soluble vitamin
a group of cobalt-containing vitamer compounds known
as cobalamins
is the largest and most structurally complicated vitamin
3 forms: cyanocobalamin, hydroxocobalamin, and
cofactor forms of B12: adenosylcobalamin,
methylcobalamin
Rols:in brain and nervous system function, and the
formation of blood.
Produced by: bacteria and archaea
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Structurecorrin ring
The central metal ion: cobalt
six coordination sites
Four sites: corrin ring
fifth site: dimethylbenzimidazole group
sixth site: is variable
-CN, -OH, -CH3 or a 5'-deoxyadenosyl
group
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Synthesis
Only bacteria and archaea have the enzymes
required for its biosynthesis
Neither plants nor animals are independently
capable of constructing vitamin B12but conversion
between different forms of the vitamin can be
accomplished in the human body
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How much vitamin B12 do I need?
The amount of vitamin B12 you need each day depends on your age.
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Birth to 6 months 0.4 mcg
Infants 7–12 months 0.5 mcg
Children 1–3 years 0.9 mcg
Children 4–8 years 1.2 mcg
Children 9–13 years 1.8 mcg
Teens 14–18 years 2.4 mcg
Adults 2.4 mcg
Pregnant teens and women
2.6 mcg
Breastfeeding teens and women
2.8 mcg
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What foods provide vitamin B12?
Vitamin B12 is found naturally in a wide variety of animal
foods and some fortified foods.
Plant foods have no vitamin B12 unless they are fortified.
Beef liver and clams
Fish, meat, poultry, eggs, milk.
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Absorption of Vitamin B12 first mechanism: Intrinsic factorsecond mechanism: transcobalamin II
Vitamin B12 IF
Parietal cell
IF receptor
StomachB12-IF complexTranscobalamin II
Epithelial cellsof terminal ileumIleum Epithelial cells
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functionCyanocobalamin
Hydroxocobalamin
two cofactor forms of B12 in the human body:
1) adenosylcobalamin(AdoB12) the cofactor of
Methylmalonyl Coenzyme A mutase (MUT) and L-α
leucine mutase.
2) methylcobalamin (MeB12), the cofactor of
enzyme Methionine synthase.
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function
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Vitamin B12 Deficiency
vitamin B12 roles neurologic function.
Deficiency of vitamin B12
DNA synthesis
macrocytic anemia
neuropsychiatric disorders
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Clinical Manifestations of Vitamin B12 Deficiency
Hematologic: Megaloblastic anemia, Pancytopenia (leukopenia,
thrombocytopenia)
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Neurologic: Paresthesias, Peripheral neuropathy
Combined systems disease (demyelination of dorsal
columns and corticospinal tract)
Psychiatric: Irritability, personality change Mild
memory impairment, dementia, Depression
Psychosis
Cardiovascular: Possible increased risk of
myocardial infarction and stroke
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Diagnosis of Vitamin B12 Deficiency
Serum B12:Normal range 200-900 (pg ml-1)
B12 deficiency < 100
Methylmalonic acid:Normal range 1.5-2.0 (mg per 24 h urine)
measurements of metabolites such as methylmalonic acid
and homocysteine have been shown to be more
Sensitive(%99.8) than measurement of serum B12 levels alone.
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Causes of Vitamin B12 Deficiency
nutritional deficiency
malabsorption syndromes
gastrointestinal causes
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Schedule for Vitamin B12 Therapy
Route ofadministration
Initial dosage Maintenance dosage
Oral 1,000 to 2,000 mcg per day for one to two weeks
1,000 mcg per day for life
Intramuscular 100 to 1,000 mcg every day or every other day for one to two weeks
100 to 1,000 mcg every oneto three months
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Medical uses
vitamin B12 deficiency
cyanide poisoning
hereditary deficiency of transcobalamin II.
High vitamin B12 level: protect against brain
atrophy or shrinkage associated with Alzheimer's
disease
High-dose administration of Vitamin B12 : stimulate
the activity of the body's TH1 suppressor T-Cells.
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Vitamin B12 and Cancer
Evidence indicates that deficiencies of iron and
zinc, and the vitamins folate, B12, B6 and C, can
cause DNA damage and lead to cancer.
Reduced folate intake has been associated with
cancer. Folate, B6 and B12 deficiencies cause the
incorporation of deoxyuracil into DNA, leading to
DNA breakage, and could promote tumorigenesis.
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Folate and vitamin B6 were inversely associated
and vitamin B12 was positively associated with
Oesophageal and gastric cancers in a case–
control study.
Dietary intakes of folate, B6 and B12 were
inversely related to the risk of developing
cervical dysplasia
No statistically significant association between
folate, B12 and cervical cancer was found