B12 3 pp - Vitamin B12 Spring 2011 Vitamin B12 History...

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Vitamin B12 Spring 2011 Vitamin B12: History • Pernicious (fatal) anemia • Irreversible neurological degeneration of nervous systems Vitamin B12: History • Minot , Murphy, Whipple 1920’s – Discovered cure for fatal disease consumption of large quantities of nearly raw liver • consumption of large quantities of nearly raw liver cured pernicious anemia Won Nobel Prize 1934
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Vitamin B12: History - Nobel prize also won for elucidating the molecular structure of B 12 (Dorothy Hodgkins) Hodgkins) - Patients could then be treated with synthetic B12 Vitamin B12: Structure
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Pharmacological Form • Cyanocobalamin most stable pharmacological form – Used in vitamin supplements and in foods that are fortified such as breakfast cereals Vitamin B12: Food Sources • Synthesized solely by microorganisms – Ruminant animals obtain B12 from microorganisms in gut • Plants do not synthesize B 12 • Only naturally occurring sources of B 12 are foods of animal origin for humans • Fruits and vegetables –n o v i t am i n B 12 unless from organisms in dirt •B e s t s o u r c e : m e a t Vitamin B12: Food Sources • Dairy products • Eggs • Seafood: shellfish very high 12 fortified products – cereals, meat substitutes, soy milk
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Vitamin B12: Absorption • Naturally occurring B12 in food – Bound to protein Mt b l d f b t i – Must be released for absorption • Gastric acid essential • Synthetic B12 in fortified foods – Not bound to protein Vitamin B12: Absorption Pepsin cleaves from dietary protein: HCl + Pepsin Di t P t i B Pt i+B Dietary Protein-B 12 Protein + B 12 Achlorhydria (reduced production gastric acid) impaired absorption common in elderly
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Vitamin B12 Absorption • Two mechanisms of absorption – Passive – Active Active Vitamin B12: Active Absorption •B 12 in stomach following release from dietary proteins – Binds to R proteins • Found in saliva and gastric juices – Pancreatic enzymes: cleave R protein Vitamin B12: Absorption • Intrinsic factor (IF) • Glycoprotein with a mw of 45,000 Da • Produced in gastric parietal cells in fundus and body of stomach • B12 binds to IF after release from R proteins • IR-B12 complex traverses the entire length of the small intestine • binds to specific receptors located on the brush border of the ileal mucosa
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B 12 B 12 B 12 R R R R Stomach B 12 •R proteins: salivary glands •Higher affinity for R proteins than IF in acid pH •Vit B12-R protein + IF moves to duodenum •B12-IF complex resistant pancreatic enzymes B 12 R B 12 Intestinal Cell (ileum) B12 IF receptor 12 Small intestine Pancreatic enzymes Recently discovered: B12 leaves cell unbound, not bound to TCII Vitamin B12: Absorption • Receptor has one subunit facing outward and one facing into the cell – receptor consists of proteins • cubulin • receptor-associated protein (RAP) • Internalization of the IF-B12 complex by ileal receptor that requires – calcium ions and neutral pH for binding Vitamin B12: Absorption •V i t B 12 -IF absorbed intact: endocytosis
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Vitamin B12 Absorption
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B12 3 pp - Vitamin B12 Spring 2011 Vitamin B12 History...

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