Transendothelial Transport and Its Role in Therapeutics
Table 3
Vitamins and their transport across the blood brain barrier (BBB); mechanisms and functions.
Fat-soluble
Transport mechanism
Physiological functions
Deficiency disease
References
Vitamin A (retinol and retinoic acid)
Vitamins show specific high-affinity to proteins which transport them. These are also transported after being mixed with lipid micelles formed with the aid of bile salts, lysolecithin, lower glycerides, and cholesterol.
Stored in liver; maintains general health and vigor of epithelial cells.
Vitamin D and its hydroxylated metabolites are transported in the blood, bound to a transport protein DBP which is also very important in the placental transfer of 25-hydroxy-vitamin Dl.
Involved in intestinal absorption of calcium and phosphorus and in calcium metabolism and bone formation.
Rickets and osteomalacia; it also affects brain development, function and its low levels cause neuropsychiatric diseases like autistic spectrum disorder and schizophrenia. Its deficiency in early life affects neuronal differentiation, axonal connectivity, dopamine ontogeny, and brain structure and function.
Intestinal absorption and transport occur with chylomicrons. Alpha-tocopherol is mostly transferred to parenchymal cells of the liver where it is stored.
Inhibit catabolism (i.e., oxidation) of certain fatty acids of cellular membranes.
Hemolytic anemia affects brain functions mainly related to mitochondrial and peroxisomes.
Vitamin K is a quinone compound in the human body in a storage form as menaquinone (MK); distribution includes regulated amounts in mitochondrial membranes. The human brain, which has low amounts of typical vitamin K dependent function (e.g., gamma carboxylase) has relatively high levels of MK, and different regions of brain have different amounts.
Required for the formation of prothrombin (an essential component of blood clotting). Coenzyme Q is a quinone synthesized de novo, and the levels of synthesis decline with age. The levels of MK are dependent on dietary intake and generally increase with age.
Sever bleeding during delivery, delayed blood clotting, MK has a characterized role in the transfer of electrons to fumarate in prokaryotes. A newly recognized fumarate cycle has been identified in brain astrocytes.
Essential for synthesis of acetylcholine; rapidly destroyed by heat, carbohydrate metabolism.
Beriberi, polyneuritis affect impulse transmission, thoughts, and intelligence.
Vitamin B2 (riboflavin)
By diffusion
Forms the coenzyme FAD which is involved in metabolism of carbohydrates and proteins.
Dermatitis, blurred vision.
Niacin (nicotinic acid)
By diffusion
Forms the coenzyme NAD which is involved in energy-releasing reactions. In lipid metabolism, it inhibits production of cholesterol and helps in fat break down.
Pellagra
Vitamin (pyridoxine)
Transported across brain and choroid plexus in nonphosphorylated B form and has separate carriers. The vitamin B6 derivative pyridoxal phosphate is a cofactor in the synthesis of GABA.
Forms coenzymes involved in amino acid metabolism in brain and is involved in fat metabolism; it imposes inhibitory effects on the brain neurons that show protective role during hypoxia or ischemia.
Convulsion, both cofactor and noncofactor vitamin (e.g., of B(1), B(3), B(6), and E) have potential role in the therapy of brain disorders.
Essential for synthesis of DNA; overcooking destroys it.
Macrocytic anaemia
Biotin (vitamin H)
By diffusion and protein transporters
Acts as coenzyme in metabolism of carbohydrates, fatty acids, and nucleic acid.
Mental depression, muscular pain, dermatitis, and nausea
Vitamin B12 (cyanocobalamin)
Vitamin B12 permease ABC protein transporter; it transports protein containing two transmembrane domains (T) and two cytosolic ATP binding domain.
Acts as coenzyme necessary for DNA synthesis, red blood cell for motion, growth, and nerve function.
Malfunctioning of CNS
Vitamin C (ascorbic acid)
Absorbs through diffusion by glucose GLUT1 transporter, glucose GLUT1 also transports dehydroascorbic acid into the brain and its transport is inhibited by d-glucose; Slc23a1 is ascorbic-acid transporter that is a Na+-dependent system.
Promotes protein synthesis (collagen), wound healing, and iron absorption; protects body against infections; rapidly destroyed by heat.
Scurvy: vitamin C crosses the placenta and is an essential requirement in the perinatal period.
