Vitamin B12:

a water soluble hematopoietic vitamin

BY
DR.SHERYAR ORAKZAI
Chemistry:

 Chemically classified as cobalamins or corrinoids.

 Composed of
1) Tetra pyrrole ring > CORRIN
2) central cobalt atoms (Corrin+Cobalt=cobamide)
3) nucleotide side chain:
4) Attached are one of following side groups:
a)methyl (methylcobalamin)
b)5’deoxy adenosine(deoxyadenosyl cobalamin)
c)Hydroxyl (hydroxocobalamin)
d)Cyanide (Cyanocobalamin)
Dietary Sources:

 product of Microbial Synthesis

 Foods of Animal origin:
Meat and meat products
Dairy products
Fish and shellfish
 Fortified ready-to-eat-cereals.
 Vegetables, fruits, and other foods of non animal origin are free from cobalamin unless
contaminated by bacteria.
Absorption:

 Two mechanisms exist for cobalamin absorption.

 • Passive absorption-occurring equally through buccal, duodenal
and ileal mucosa; it is rapid but extremely inefficient, <1 percent
of an oral dose being absorbed by this process.
 • Active absorption-The normal physiologic mechanism is active;
it occurs through the ileum and is efficient for small (a few
micrograms) oral doses of cobalamin and is mediated by gastric
intrinsic factor (IF).
Continue…

 Dietary cobalamin is released from protein complexes by enzymes

in the stomach, duodenum, and jejunum
 • It combines rapidly with a salivary glycoprotein that belongs to
the family of cobalamin-binding proteins known as haptocorrins
(HCs).
 • In the intestine, the haptocorrins are digested by pancreatic
trypsin and the cobalamin transferred to intrinsic factor(IF).
Role of Intrinsic Factor:

 Intrinsic factor (IF) is produced in the gastric parietal cells of the

fundus and body of the stomach, its secretion parallels that of
hydrochloric acid.
 The IF-cobalamin complex passes to the ileum, where IF attaches
to a specific receptor (Cubulin) on the microvillus membrane of
the enterocytes.
 Cubulin with its ligand IF-cobalamin complex is endocytosed.
 The cobalamin-IF complex enters the ileal cell where IF is
destroyed.
Transport:

 Three plasma transport proteins have been identified.

 Transcobalamin I and III (differing only in carbohydrate structure)

are secreted by white blood cells.

 Although approximately 90 percent of plasma vitamin B12 circulates

bind to these proteins, only transcobalamin II is capable of
transporting vitamin B12 into cells.
Functions:

 Required for DNA synthesis and red cell maturation

 Required for conversion of
 1) L-methylmalonyl Co-A to succinyl Co-A
 2) homocysteine to methionine.
 Congenital defects in mutase synthesis or inability to synthesize Adenosyl-
Cbl leads to methylmalonic aciduria and metabolic ketoacidosis.
 Congenital defects in methionine synthase or synthesis of methyl-Cbl leads
to Hyperhomocysteinemia. Premature Coronary Artery Disease Peripheral
Vascular Disease
Functions:
Recommended Daily Intake:

 Vitamin B12 For Adults Men : 2.4 micrograms

 Vitamin B12 for Pregnant women: 2.6 micrograms
 Vitamin B12 for Lactating mother: 2.8 micrograms
Causes of Vitamin B12 Deficiency:

 Dietary deficiency (rare)

 Decreased production of intrinsic factor
 Pernicious anemia
 Gastrectomy
 Pancreatic insufficiency
 Fish tapeworm (rare)
 Helicobacter pylori infection
Other Groups At Risk of Deficiency:

 Older than 65 years of age

 Malabsorption
 Who are vegetarians
 Infants with metabolic disorders.
 Taking prescribed medications
 1)nitrous oxide
 2)Phenytoin
 3)Dihydrofolate reductase inhibitors
 4)metformin
 5)Proton pump inhibitors
Vitamin B12 Deficiency:

 1) Megaloblastic anemia is a subgroup of macrocytic anemias

 Megaloblastic erythropoiesis when defect in DNA synthesis and
the cells are arrested at the G2 phase
 A buildup of cells occurs that do not synthesize DNA so nucleus
develops at a slower rate than the rest of the cell
 Cytoplasm continues to grow due to RNA synthesis
 Cells become larger and megalblastic
 Morphologic changes in blood:
 1) hyper segmentation of Neutrophil
 2) Macrocytosis
 3) Anemia
 4) Leukopenia
 5) thrombocytopenia
 6) megaloblastic changes in bone marrow
 All bone marrow lesions are reversed with Vit B12 therapy
Continue:

 2) Demyelinating disorder of Central Nervous System:

Burning pain
Loss of sensation in extremities
Weakness
Spasticity and paralysis
Confusion
Disorientation
dementia
>this disorder has been given the name
SUBACUTE COMBINED DEGENERATION OF SPINAL CORD
TOXICITY:

 No adverse effects have been associated with excess viatamin

B12 intake from food or supplements in healthy people.
Laboratory Assessment of Status:

 Indirect Tests :
1) assays for Urinary and serum concentration of
methylmalonic acid.
2) assays for plasma Homocysteine.
3) deoxy uridine suppression test.
4) Vitamin B12 absorption test.(Schilling test)
5) Measurement of Holotranscobalamin II: specific marker for
biologically available B12.
 Direct Tests:
 1) Microbiological competitive protein binding (CPB)
reference method for biologically active Vitamin B12.
 2) Chemiluminescece Microparticle immunoassay(CMIA)
 Normal: >300 pg/mL (>221 pmol/L) 
 Borderline:200 to 300 pg/mL (148 to 221 pmol/L)  
 Vitamin B12 Def: <200 pg/mL (<148 pmol/L)  
 For Borderline cases:
 Homocysteine raised but normal methylmalonic acid: Folate
Deficiency
 Homocysteine and methylmalonic acid : B12 Def
THANK YOU