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2 Vitamin B12 By:Zahra Mahboob

Introduction Structure Synthesis Sources Absorbtion Function Deficiencies Treatment Vitamin B12 and Cancer 3 Outline …

Introduction a 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 B 12: adenosylcobalamin, methylcobalamin Rols:in brain and nervous system function, and the formation of blood. Produced by: bacteria and archaea 4

Structure corrin ring The central metal ion: cobalt six coordination sites Four sites: corrin ring fifth site: dimethylbenzimidazole group sixth site: is variable -CN, -OH, -CH 3 or a 5'-deoxyadenosyl group 5

Synthesis Only bacteria and archaea have the enzymes required for its biosynthesis Neither plants nor animals are independently capable of constructing vitamin B 12 but conversion between different forms of the vitamin can be accomplished in the human body 6

How much vitamin B12 do I need? The amount of vitamin B12 you need each day depends on your age. 7

Birth to 6 months0.4 mcg Infants 7–12 months0.5 mcg Children 1–3 years0.9 mcg Children 4–8 years1.2 mcg Children 9–13 years1.8 mcg Teens 14–18 years2.4 mcg Adults2.4 mcg Pregnant teens and women2.6 mcg Breastfeeding teens and women 2.8 mcg 8

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. 9

Absorption of Vitamin B12 first mechanism: Intrinsic factor second mechanism: transcobalamin II 10 Vitamin B12 IF Parietal cell IF receptor StomachB12-IF complex Transcobalamin II Epithelial cells of terminal ileum IleumEpithelial cells

function Cyanocobalamin Hydroxocobalamin two cofactor forms of B 12 in the human body: 1) adenosylcobalamin(AdoB 12 ) the cofactor of Methylmalonyl Coenzyme A mutase (MUT) and L-α leucine mutase. 2) methylcobalamin (MeB 12 ), the cofactor of enzyme Methionine synthase. 11

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Vitamin B12 Deficiency vitamin B12 roles neurologic function. Deficiency of vitamin B12 DNA synthesis macrocytic anemia neuropsychiatric disorders 14

Clinical Manifestations of Vitamin B12 Deficiency Hematologic: Megaloblastic anemia, Pancytopenia (leukopenia, thrombocytopenia) 15

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 16

Diagnosis of Vitamin B12 Deficiency Serum B12:Normal range (pg ml -1 ) B12 deficiency < 100 Methylmalonic acid:Normal range (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. 17

Causes of Vitamin B12 Deficiency nutritional deficiency malabsorption syndromes gastrointestinal causes 18

Schedule for Vitamin B12 Therapy 19 Route of administration Initial dosageMaintenance dosage Oral1,000 to 2,000 mcg per day for one to two weeks 1,000 mcg per day for life Intramuscular100 to 1,000 mcg every day or every other day for one to two weeks 100 to 1,000 mcg every one to three months

Medical uses vitamin B 12 deficiency cyanide poisoning hereditary deficiency of transcobalamin II. High vitamin B 12 level: protect against brain atrophy or shrinkage associated with Alzheimer's disease High-dose administration of Vitamin B 12 : stimulate the activity of the body's TH1 suppressor T-Cells. 20

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. 21

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 22