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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