Absorption, transport and metabolism of vitamin E Domina Petric, MD

Absorption of vitamin E 11/11/2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Micelle-dependent passive diffusion Vitamin E is absorbed from the upper small intestine by nonsaturable passive diffusion dependent on micellar solubilization and the presence of bile salts and pancreatic juice. The primary site of absorption appears to be the medial small intestine. Esterified forms of the vitamin E are hydrolyzed, probably by a duodenal mucosal esterase. The predominant forms absorbed are free alcohols. 11/11/2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Micelle-dependent passive diffusion The enteric absorption of vitamin E is dependent on the adequate absorption of lipids. The process requires the presence of: fat in the lumen of the gut secretion of pancreatic esterases for the release of free fatty acids from dietary triglycerides bile acids for the formation of mixed micelles esterases for the hydrolytic cleavage of tocopheryl esters when those forms are consumed 11/11/2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Micelle-dependent passive diffusion Individuals unable to produce pancreatic juice or bile (patients with biliary obstruction, cholestatic liver disease, pancreatitis, cystic fibrosis) can be expected to show impaired absorption of vitamin E, as well as other fat-soluble nutrients that are dependent on micelle-facilitated diffusion for their uptake. 11/11/2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Micelle-dependent passive diffusion Other food components can interfere with the utilization of dietary vitamin E. Polyunsaturated fatty acids, particularly fish oils, can impair vitamin E retention. Green tea catechins can interfere with the enteric absorption of tocopherols. 11/11/2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Micelle-dependent passive diffusion Absorbed vitamin E, like other hydrophobic substances, enters the lymphatic circulation in association with the triglyceride-rich chylomicra. The kinetics of vitamin E absorption are biphasic, reflecting the initial uptake of the vitamin by existing chylomicra followed by a lag phase due to the assembly of new chylomicra and intestinal VLDLs. 11/11/2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Micelle-dependent passive diffusion Within the enterocytes vitamin E combines with other lipids and apolipoproteins to form chylomicra and very low-density lipoproteins (VLDLs). Chylomicron are released into the lymphatics. 11/11/2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Transport of vitamin E II. 11/11/2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Transport of vitamin E The metabolism of ciculating chylomicra can result in tocopherols being transferred directly to tissues by partitioning into their plasma membranes, or indirectly by transfer to and between ciculating lipoproteins. 11/11/2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Transport of vitamin E Vitamin E does not appear to have a specific carrier protein in the plasma. It is rapidly transferred from chylomicra to plasma lipoproteins to which it binds nonspecifically, whereupon it is taken up by the liver and is incorporated into nascent VLDLs (with selectivity in favor of α- tocopherol over the γ-vitamer) secreted by the liver. 11/11/2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Transport of vitamin E The majority of the triglyceride-rich VLDL remnants are returned to the liver. Some of the remnants are converted by lipoprotein lipase to LDLs. It appears that, during this process, vitamin E also transfers spontaneously to apolipoprotein B-containing lipoproteins, including the very low density lipoproteins (VLDLs), low-density lipoproteins (LDLs) and high-density lipoproteins (HDLs). 11/11/2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Transport of vitamin E These transport processes can be disrupted under hyperlipidemic conditions. Patients with hypercholesterolemia and/or hypertriglyceridemia show reduced plasma uptake of newly absorbed vitamin E. Transport can also be disrupted by impairments in the expression of apolipoprotein B. Patients with apobetalipoproteinemia become vitamin E-deficient due to very low rates of uptake regardless of dietary vitamin E status. 11/11/2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Transport of vitamin E Tocopherol exchanges rapidly between the lipoproteins and erythrocytes: about one-fourth of total erythrocyte vitamin E turns over every hour. The concentrations of vitamin E and of erythrocytes in plasma are highly correlated: the erythrocytes contain 15-25% of total vitamin E in the plasma. 11/11/2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Transport of vitamin E Vitamin E is membrane protective. Plasma tocopherol levels are inversely related to susceptibility to oxidative hemolysis. This relationship makes the plasma α-tocopherol level useful as a parameter of vitamin E status. In healthy people, values ≥0.5 mg/dl are associated with protection against hemolysis and are taken to indicate nutritional adequacy. 11/11/2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Transport of vitamin E Maternal tocopherol levels increase during pregnancy, but fetal levels remain low, suggesting a barrier to transplacental movement of the vitamin. Because apolipoprotein E (apoE) affects the hepatic binding and catabolism of several classes of lipoproteins, it has been suggested that it can also affect the metabolism of tocopherols. 11/11/2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Cellular uptake Uptake mediated by lipid transfer proteins and lipases. Uptake of α-tocopherol from the amphipathic lipoprotein outer layer is mediated in a directional way by phospholipid transfer protein and by way of lipoprotein lipase mediated exchange of α-tocopherol from chylomicra and lipoprotein remodeling. This lipase is thought to be involved in the transport of α-tocopherol across the blood–brain barrier and into the central nervous system. 11/11/2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Cellular uptake Receptor-mediated endocytosis of vitamin E-carrying lipoproteins. Binding of lipoproteins to specific cell surface receptors must occur to allow vitamin E to enter cells either by diffusion and/or bulk entrance of lipoprotein-bound lipids. Deficiencies in this pathway do not necessarily reduce tissue tocopherol levels. 11/11/2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Cellular uptake Selective lipid uptake. Evidence has been presented for the receptor- mediated uptake of lipoprotein-bound α-tocopherol without uptake of the apolipoprotein, in the manner described for the cellular uptake of cholesterol from HDLs. The process appears to involve the scavenger receptor class B type I (SR-BI). 11/11/2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Tocoferol transfer proteins α-tocopherol transfer protein tocopherol-associated proteins 11/11/2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Vitamin E storage In most non adipose cells, vitamin E is localized almost exclusively in membranes. Kinetic studies indicate that such tissues have two pools of the vitamin: labile, rapidly turning over pool fixed, slowly turning over pool 11/11/2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Vitamin E storage The labile pools predominate in such tissues as plasma and liver, as the tocopherol contents of those tissues are depleted rapidly under conditions of vitamin E deprivation. In adipose tissue vitamin E resides predominantly in the bulk lipid phase, which appears to be a fixed pool of the vitamin. 11/11/2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Vitamin E storage After a change in α-tocopherol intake, adipose tissue tocopherols may not reach a new steady state for two or more years. Neural tissues also exhibit very efficient retention (very low apparent turnover rates) of vitamin E. 11/11/2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Metabolism of vitamin E III. 11/11/2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Limited metabolism The metabolism of vitamin E is limited. Most tocopherols that are absorbed and retained are transported without transformation to the tissues. The actual metabolism of tocopherols involves head-group and side-chain oxidation. 11/11/2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Metabolism of vitamin E Oxidation of the chromanol ring Oxidation of the phytyl side chain 11/11/2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Oxidation of the chromanol ring Oxidation of the chromanol ring is the basis of the in vivo antioxidant function of the vitamin. It involves oxidation primarily to tocopherylquinone, which proceeds through the semis table tocopheroxyl radical intermediate. Tocopherylquinone can be partially reduced to α-tocopherylhydroquinone, which can be conjugated with glucuronic acid and secreted in the bile. Excretion with the feces is the major route of elimination of the vitamin E. 11/11/2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Oxidation of the phytyl side chain Vitamin E is catabolized to water-soluble metabolites by a cytochrome P450-mediated process initiated by a β-hydroxylation of a terminal methyl group of the phytyl side chain. The resulting metabolites include tocopheronic acid and tocopheronolactone excreted in the urine often as glucuronyl conjugates. 11/11/2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Vitamin E recycling A significant portion of vitamin E may be recycled in vivo by reduction of tocopheroxyl radical back to tocopherol. 11/11/2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Literature Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008. 11/11/2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.