Updated: 03/11/08 02:32 PM
HOME HEAL EDUCATE RESEARCH DIRECTORY OUTREACH


Authors: D.R. Saunders, C.E. Rubin, and J.D. Ostrow
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S. Normal Vitamin Absorption

DAKE require efficient luminal and mucosal processing for optimal absorption. The fat soluble vitamins, D, A, K and E, have such limited water-solubility that they must be solubilized in bile salt-mixed micelles to be transported across the unstirred water layer to the small intestinal absorptive cells. In general terms, DAKE absorption across the brush border membrane is facilitated by carrier proteins. Within the enterocyte, DAKE are packaged in chylomicrons which exit into intestinal lymph prior for distribution to peripheral tissues. DAKE in chylomicron remnants are taken up by hepatocytes for metabolism and storage, or for export within VLDL or as complexes with carrier proteins. DAKE are excreted into bile, and are reabsorbed from the small intestine so that there is an enterohepatic circulation of these vitamins.

Liver, carrots, eggs, milk are good sources of vit. A Dietary sources of vitamin A include retinol esters of long-chain fatty acids in animal tissues, and carotenoids in fruits and vegetables. In the small gut, retinyl esters are hydrolysed by pancreatic and brush border esterases. Retinol and carotene are solubilized in mixed micelles. Within the enterocytes, retinol is reesterified with long chain fatty acids and then packaged in the lipid core of chylomicrons. In vitamin A-replete animals, retinyl esters are stored in stellate cells within the liver. the liver.

Normal D absorption requires mixed micelles 25(OH) D3 is useful as an oral agent because it is absorbed more readily than D3 Vitamin D excreted in bile can be reabsorbed








Animal tissues contain K1 and K2 		Vitamin D includes several compounds such as D3 (cholecalciferol) which is synthesized in the skin by the action of UV light on 7-dehydrocholesterol. D2 (ergocalciferol) is formed in plants. In the U.S. foods are fortified with D2 or D3 which follow the usual pathways for fatty substances of digestion and absorption. Two hydroxylations are required to generate the metabolically active form of vitamin D. The first hydroxylation occurs in the liver. The product, 25-OH-D3, is converted by the kidneys into 1,25-(OH)2- D3, which regulates calcium metabolism as part of a complex endocrine system. Vitamin D3 and its hydroxylated metabolites are excreted in bile so there is an enterohepatic circulation of these compounds.

Vitamin K refers to a group of substances which have a naphthoquinone ring. Phylloquinone (Vit K1) is found in plants while menaquinones (Vit K2) are synthesized by bacteria. Menadione (K3) is a synthetic compound. Therapeutic vitamin K is phylloquinone.

Bile salt mixed micelles are essential for the solubilization of water-insoluble phylloquinone which is transported in chylomicrons to the liver. It is likely that there is an enterohepatic circulation of Vit K, but we are uncertain if bacterial menaquinones can be absorbed from the colon. The anticoagulant, warfarin, interferes with the hepatic metabolism of vitamin K so that the production of clotting factors diminishes.

Vegetable oils are main dietary source of vitamin E. Vitamin E is a major lipid-soluble antioxidant in plasma and in cell membranes. There are eight forms of vitamin E, but alpha tocopherol acetate is often used as a dietary supplement.

The water-soluble vitamins are usually present in our diets as proteinaceous complexes which must be digested by luminal or brush border enzymes prior to absorption. Transport requires membrane carriers, and specific binding proteins and receptors.


Liver, yeast, leafy vegetables, fruits



Daily requirement is 50 micrograms



Folate has an EHC 		Folates are a family of compounds whose prototype is pteroylglutamic acid (folic acid). Naturally occurring folates contain up to nine glutamate moieties which must be removed by brush border folate conjugase to yield absorbable monoglutamyl folate. At physiological concentrations, monoglutamyl folate is transported by specific membrane carriers. Folic acid can diffuse across the mucosa when therapeutic doses are given. Folic acid is transported from the intestine in portal blood. A substantial amount of folate is excreted into bile; this biliary folate can be reabsorbed by the small intestine to maintain folate balance. Folates serve as coenzymes in biochemical reactions that transfer one-carbon units which are crucial for nucleic acid synthesis.

Folate deficiency impairs cell division Clinical manifestations of folate deficiency are highlighted by macrocytic anemia. The bone marrow contains abnormal precursors of red cells, neutrophils, and platelets because DNA synthesis is defective.

Cyanocobalamin is a stable form of B12 used therapeutically Patients with achlorhydria have difficulty absorbing food-bound Vit B12 IF is a glycoprotein Vit B12 absorption can be impaired in pancreatic insufficiency Vitamin B12 is synthesized only by microorganisms, and in our diet it is supplied nearly exclusively by animal foods. Meat contains adenosyl-, and hydroxycobalamin; dairy products contain methyl-, and hydroxycobalamin. These protein-bound forms of Vit B12 are digested by gastric acid and pepsin so that the Vit B12 is released into gastric juice where it becomes bound to a salivary B12 binding protein (haptocorrin) rather than to gastric intrinsic factor (IF). Secretion of IF from parietal cells is stimulated by the same agents that stimulate acid secretion, but drugs such as omeprazole which inhibit the H+/K+ pump do not block IF secretion. Haptocorrin and IF are not digested by acid-pepsin, but pancreatic proteases can digest haptocorrin, but not IF. Therefore, in the duodenojejunal lumen, Vit B12 is transferred from haptocorrin to IF. The Vit B12-IF complex binds to a specific receptor in the brush border of ileal absorptive cells. The Vit B12-IF complex enters the ileal absorptive cells by endocytosis and Vit B12 is transferred to transcobalamin which exits through the basolateral membrane into portal venous blood.




There is an EHC for Vit B12 		Hepatocytes secrete Vit B12 into bile and biliary B12 can be reabsorbed by ileal mucosa. This enterohepatic circulation of Vit B12 helps to maintain normal body stores of the vitamin. Patients who have had an ileal resection may become B12-deficient in 2-3 years. Subjects ingesting a Vit B12-deficient diet may require 10-20 years to manifest B12-deficiency because they are able to conserve biliary Vit B12.



Daily requirement is 1 microg of Vit B12 		Vit B12 is a cofactor for two enzymatic reactions which maintain the supply of methionine and tetrahydrofolate, and which promote the synthesis of succinyl co-enzyme A. Vit B12 deficiency leads to macrocytic anemia, and to neuropsychiatric abnormalities.

Absorption of free cobalamin will be abnormal when parietal cells are absent Absorption of Vit B12 can be assessed by a Schilling test in which a patient can be given 58Co-labelled free cobalamin, and IF-bound 57Co-cobalamin orally. The urinary excretion of the two isotopes can distinguish between IF deficiency and ileal disease.

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