Absorbce vitamínu E enterocyty
Absorpce v GIT obecně
- In fact, no specific plasma transport proteins for alpha-tocopherol have been described
- VE transport in blood shares the cholesterol and lipoprotein pathways [8]
- Flux of lipoproteins toward the liver facilitates hepatic VE delivery
Kde
- Upper gastrointestinal tract
Co
- Všechny homologní varianty vit. E bez rozdílu [1]
Efficient alpha-tocopherol absorption
- Requires the presence of fat [10]
Average alpha-tocopherol absorption
- From a usual diet is about 75 %
- Observed in two balance studies
- Kinetic study using a multi-compartmental model of alpha-tocopherol metabolism [2]
- Is consistent with the high efficiency of lipid absorption from the diet (EFSA NDA Panel, 2010) [2]
- 2H-labelled RRR-alpha-tocopheryl acetate
- 150 mg 8 healthy subjects consuming with four different test meals (Jeanes et al., 2004)
- 3H-labelled all-rac-alpha-tocopherol
- (0.2 mg) in oily solution in humans
- Mean fractional absorption of alpha-tocopherol of 75 % (range: 61–90 %) in normal adults (Kelleher and Losowsky, 1968) [2]
- 3–6 µg in 1 mg unlabelled form, consumed with milk
- Mean fractional absorption was cca 69 % (range: 55–79 %) in normal adults (MacMahon and Neale, 1970) [2]
- 14C-labelled RRR-alpha-tocopherol mixed with milk (2 % fat) 0.78 µg before breakfast (containing 8 g fat)
- 12 healthy adults (Novotny et al., 2012)
- Mean absorption (± SD) of the labelled alpha-tocopherol dose was calculated to be 80.8 ± 5.98 %.9 [2]
- D6-RRR-alpha-tocopheryl acetate10 (22 mg per 80 g serving) aplle fortification
- Five healthy adults consumed apples fortified with vit.E in controlled breakfasts
- Containing 0 %, 6 % or 21 % of energy from fat (Bruno et al., 2006b)
- Mean absorption of the labelled alpha-tocopherol increased
AUC
- Calculation of the area under the curve
- Would have been a better method than the estimation from the
- Plasma Cmax of the labelled alpha-tocopherol multiplied by the plasma volume [2]
- Studies on alpha-tocopherol absorption used
- Different models and techniques
- Wide-ranging doses of labelled alpha-tocopherol (0.78 µg to 22 mg)
- Embedded into different food matrices and test meals [2]
- Large range of reported mean alpha-tocopherol absorption
- 10- 80 % for different fat intakes [2]
Emulsification
- žluč !
Transport through the unstirred water layer
Emulsification
- žluč ! requires bile acids [10] - s tukem
Transport through the unstirred water layer
Lipázy
- Pancreatic enzymes [10]
Enterocyty
Uptake by the apical membrane of the enterocyte
- Pasivní difuze v tenkém střevu
- Transporters non-specific to alpha-tocopherol (Rigotti, 2007; Iqbal and Hussain, 2009; Reboul et al., 2011) [2]
- Involved in VE uptake on the apical side of the enterocyte
- Share common uptake pathways
- Clearly associated with the transmembrane transport of cholesterol and other lipophilic components such as VE [8]
Niemann–Pick C1 (NPC1) - Niemann–Pick disease type C1 (NPC1)
- Membrane protein that is highly expressed in the
- Intestine,
- Macrophages,
- Liver
- Crucial role in the absorption and movement of lipophilic compounds across cell membranes [8]
- Number of mutations in the NPC1 gene have been associated with
- Lysosomal storage disorders [8]
- obesity
- NPC1 is the pharmacological target of ezetimibe
- Inhibitor of cholesterol endocytosis
- Widely used for treatment of this dyslipidemia [8]
- Inhibition of alpha-tocopherol absorption [8] suggests the involvement of NPC1 in dietary VE uptake
- Alpha-tocopherol is known to bind competitively with cholesterol at the N-terminal domain of NPC1
- Essential for the endocytosis of both compounds into the cell [8]
- In vitro experiments using Caco-2 cells transfected with plasmids overexpressing the genetic non-synonymous variants found
- In low cholesterol absorbers, showed less transport activity of both cholesterol and alpha-tocopherol
Scavenger receptor class B type 1 (SR-B1)
- Only known bidirectional integral membrane protein in the apical site of enterocytes [8]
- Mediates cholesterol transfer to and from HDL
- SR-B1 is involved in the uptake of:
- The main forms of VE from the diet
- Transport from the basolateral site of enterocytes to the blood [8]
Cluster determinant 36 (CD36)
- Membrane glycoprotein
- Involved in a wide range of functions in different cell types
- Leading role in the coordination of the uptake and processing of fatty acids (FA)
- Expressed on the apical side of enterocytes of the proximal intestine
- Interacts with dietary FA released from the digestion of triglycerides
- Facilitating VE uptake and chylomicron assembly [8]
- Uptake of long-chain free FA to drive beta-oxidation in myocytes [8]
- Storage of free FA in adipocytes [8]
- Recognizes a number of lipid compounds
- cholesterol
- Carotenes
- Binds native and oxidized lipoproteins
- Promoting cellular adhesion and internalization of oxidized LDL (ox-LDL) in monocytes [8]
- Contributes directly or indirectly to the transport [8] and internalization of VE [8]
- Seems to be a key element in the detection of the taste of fat
- Lingual and intestinal fat sensing [8]
- Genetic variants related to the concentration of CD36
- Associated with differences in creaminess perception regardless of fat content
- Increased body weight, and waist circumference [8]
- Expression of CD36 is reduced by alpha-tocopherol
- VE reduces the uptake of ox-LDL by inhibiting CD36 expression [8]
ATP-binding cassette transporter A1 (ABCA1)
- 220-kDa member of the ABCA transporter family
- Highly expressed in
- Liver, glands, intestine, and macrophages
- Hepatic outflow of
- cholesterol and phospholipids onto apolipoprotein A-1 (Apo-AI)
- Forming nascent high-density lipoprotein (HDL) particles [8]
- In intestine, ABCA1 located in the basolateral membrane of enterocytes
- Crucial for absorption, transport, and secretion into the circulation of
- cholesterol,
- Phospholipids,
- Other lipophilic compounds
- Mainly packaging them into HDL particles [8]
- ABCA1 is also responsible for the secretion of VE into portal blood in the form of intestinal HDL [8]
- Tangier disease’s patients
- Deficiency of the ABCA1 gene
- Absence of serum HDL, hypertriglyceridemia, and reduction in LDL serum levels
- Ectopic accumulation of cholesteryl esters
- Higher incidence of coronary heart and artery disease [8]
VE enterocyte internal carriers
- Still not clear
NPC1 and NPC2 may play such a role
Solubilisation into intestinal lipoproteins
Secretion out of the intestinal cell
- Into the lymph
- Into the portal vein (Bender, 2003; Borel et al., 2013) [2]
Basolateral side of the enterocyte - Sekrece
- Most of the VE is secreted in the chylomicron fraction [8]
ABCA1
- Low percentage of VE is incorporated and secreted into intestinal high-density lipoprotein (HDL) [8]
Apo-AI
- Mediates the alpha-tocopherol efflux from intestine cells to HDL [8]
- Contributes to VE secretion into intestinal high-density lipoprotein (HDL)
- Main protein component of nascent and mature HDL
- Synthesized in the
- Liver (80%)
- Small intestine (10%)
- Cofactor for lecithin cholesterol acyltransferase
- Supports cholesterol efflux from tissues [8]
- Allows the movement of VE from the enterocyte into the bloodstream
- Also present in mature HDL particles
- Favors the reverse transport of cholesterol and tocopherol from the tissues to the liver [8]
Z GIT do krve - Chylomikrony
- 81 % of ingested dose of VE [2]
- Main fraction of absorbed tocopherols and tocotrienols
- Via the apolipoprotein B pathway
- Only a small fraction via an apolipoprotein A I pathway (Reboul et al., 2009; Shichiri et al., 2010)
- Chylomikrony s vit. E
- Lymphatic pathway - secreted into the systemic circulation
- Vena portae
- Do cirkulace
