Vstřebávání vitamínu C

P.o. podání

• Jen omezený vzestup sérové hladiny askorbátu

Vstřebávání z GIT

• At moderate intakes of 30–180 mg/day
• Approximately 70%–90% of vitamin C is absorbed [12]
• Z jednotlivé dávky 200 mg
• Se vstřebá 100 %
• Z 1 g
• Méně než 50 % [1]
• Doses above 1,000 mg/day
• Absorption falls to less than 50% [12]

Transportní molekuly

• Koncentrace v růz. tkáních úzce regulována aktivními transportními syst.

Blood-brain barrier a vstup vit. C do CNS

• To maintain the internal microenvironment of the CNS
• Mediating the selective transport of nutrients, ions, waste products, drugs, and other
• ascorbate can penetrate into the CNS through the choroid plexus
• It cannot cross through the blood-brain barrier
• Tight junctions of the endothelium do not allow ascorbate transport through the paracellular pathway [11]
• Formed by three cells
• SVCT2 is not expressed in these cells [11]
• DHA can cross the blood-brain barrier through GLUT1
• Is not the main pathway through which ascorbate reaches the CNS
• Could be an important route from a therapeutic point of view
• Different doses of DHA intravenously before and after the induction of a stroke in mice
• DHA had a neuroprotective effect directly proportional to the dose administered
• Protective effect was significant whether DHA was injected before or after the stroke [11]

Endothelium of the microvasculature of the brain

Pericytes

• Involved in maintaining the structural integrity of the vessel wall
• Regulating angiogenesis
• Neuroimmunological effect
• Ability to phagocytize [11]

Astrocytes

• Astrocytes may induce
• Formation of the tight junctions between endothelial cells
• Influence the characteristic phenotype of the transporters of the blood-brain barrier
• GLUT1
• Amino acid transporter L1 [11]

Ascorbate distribution in the brain

• Not uniform
• Highest concentration of vitamin C
• Even in these structures the distribution is not homogeneous [11]
• Amygdala
• Hippocampus
• Hypothalamus [11]
• Medial nucleus has a greater concentration of ascorbate in the hypothalamus than in
• Preoptic nucleus
• Posterior nucleus
• Substantia nigra
• Brain region with the lowest concentration of ascorbate
• Could be considered a susceptibility factor for oxidative stress
• Synthesis of dopamine is pro-oxidant and needs ascorbate
• Requirements of ascorbate that dopaminergic neurons need may be the cause of the low ascorbate levels found [11]

Průnik přes endothelial barrier of each tissue

• Primarily through a paracellular pathway (except in CNS)
• Transcellular transport is not correlated with the ascorbate transferred across the endothelium
• Process may be influenced by the rigidity conferred by ascorbate to the cytoskeleton of the cells forming the barrier [11]

Do střevního endotelu

Askorbát

• Opposite to that of glucose
• ascorbate is better absorbed in ileum (glukoza lepe v duodenu) [11]

DHA

• Better absorbed in the jejunum
• Very little in the distal segments of the ileum [11]
• Part of the DHA absorbed corresponds to
• ascorbate oxidized in the lumen [11]

Uvnitř enterocytu

• DHA is reduced to ascorbate inside the enterocyte
• By complex recycling mechanisms [11]
• Then it exits the cell into the extracellular space
• Reaches the bloodstream through fenestrated capillaries in the mucosa of the small intestine [11]

Glucose transporters (GLUTs)

• Described 14 GLUT proteins
• Family of solute carriers
• Group 2A (SLC2A) [11]
• Own characteristics and a specific tissue distribution
• DHA transport by a facilitated, saturable diffusion mechanism by some GLUT transporters
• Na+ independent [11]

GLUT1 and GLUT3, and to a lesser extent GLUT4 ve střevě

• Capacity to transport DHA [11]
• Dehydroascorbic acid is absorbed in higher rate than ascorbate
• Amount of dehydroascorbic acid found in plasma and tissues under normal conditions is low [12]
• Cells rapidly reduce dehydroascorbic acid to ascorbate [12]

GLUT8 and GLUT2

• Transport DHA into rat enterocytes has been shown
• Also present in the human small intestine [11]

GLUT1 isoform

• Widely expressed in the body
• Endothelial cells of the blood-brain barrier [11]

GLUT3

• High affinity transporter (low Km)
• In neuronal cells
• In sperm, embryos
• In leukocytes [11]

GLUT4

• Mainly in adipocytes and in skeletal and cardiac muscles
• Found mostly within intracellular vesicles
• Attach to the plasma membrane in response to insulin [11]

GLUT 2

• Low affinity transporter (Km ~ 17 mM)
• In hepatocytes
• Enterocytes of the small intestine
• Proximal tubular cells
• Beta-pancreatic cells [11]

GLUT8

• In skeletal muscle, heart
• Small intestine
• Brain
• Testis
• Expression in testis can be suppressed by estrogens [11]

SVCT1 a SVCT2 Sodium-dependent vitamin C transporters (SVCTs)

• Sodium-dependent
• Energy-requiring
• Carrier-mediated transport
• Počet
• Aktivita
• Zvyšováním D klesá [1]
• Glycoproteins that transport ascorbate into the cell [11]
• Secondary active, saturable Na+-dependent transport [11]
• Red blood cells lose SVCT proteins during maturation [12]

SVCT1

• Gene that belongs to the family of solute carriers
• Group 23A, member 1 (SLC23A1) of 1797 bp [11]
• SVCT1 transports ascorbate nine times faster [11]
• Km 252.0 uM for SVCT1 [11]
• Mostly in epithelial tissues
• Small intestine
• Proximal tubule of the nephron [11]
• Where a transport of ascorbate is greater than that required by the cells [11]
• SVCT1 is found in the apical side of enterocytes [11]

SVCT2

• Member of SLC23A2
• Gene of 1952 bp
• Higher affinity for ascorbate
• Km of 21.3 uM for SVCT2 [11]
• Mainly in
• Brain,
• Skeletal muscle,
• Placenta
• Eye [11]
• Maintain adequate tissue concentrations [11]
• SVCT2 is present in the basolateral membrane of enterocytes [11]