REVIEW: Vitamin transport and homeostasis in mammalian brain: focus on Vitamins B and E

Abstract

With the application of genetic and molecular biology techniques, there has been substantial progress in understanding how vitamins are transferred across the mammalian bloodbrain barrier and choroid plexus into brain and CSF and how vitamin homeostasis in brain is achieved. In most cases (with the exception of the sodium-dependent multivitamin transporter for biotin, pantothenic acid, and lipoic acid), the vitamins are transported by separate carriers through the blood-brain barrier or choroid plexus. Then the vitamins are accumulated by brain cells by separate, specialized systems. This review focuses on six vitamins (B 1 , B 3 , B 6 , pantothenic acid, biotin, and E) and the newer genetic information including relevant 'knockdown' or 'knockout' models in mice and humans. The overall objective is to integrate this newer information with previous physiological and biochemical observations to achieve a better understanding of vitamin transport and homeostasis in brain. This is especially important in view of the newly described non-cofactor vitamin roles in brain (e.g. of B 1 , B 3 , B 6 , and E) and the potential roles of vitamins in the therapy of brain disorders.

Mice lacking α-tocopherol transfer protein gene have severe α-tocopherol deficiency in multiple regions of the central nervous system

“…If α-TTP is essential for the retention of α-T (Meier et al, 2003;Spector and Johanson, 2007) then we would predict higher expression of α-TTP in the cortex compared to that in the cerebellum. Experimental data do not support this prediction.…”

Understanding the functions and relationships of the glymphatic system and meningeal lymphatics

“…CSF and its constituents can act directly on brain function. Notably, vitamin C and folate diffuse into the brain through the CSF (93,94). Many other ions and proteins are transported through the choroid plexus epithelium and diffuse from the CSF into the brain, where they affect neuronal function (94).…”

Vitamin B-6 Metabolism and Interactions with TNAP

“…Seargeant and Stinson (1979) estimated that inorganic phosphate concentrations in liver would be high enough to inhibit human liver alkaline phosphatase if the phosphate was accessible to the enzyme. Spector and Johanson (2007) noted that there are five general processes that must be understood to explain mechanistically vitamin homeostasis in brain:…”

“…The rabbit choroid plexus can also absorb unphosphorylated vitamers from the CSF. Since the nonphosphorylated vitamers are removed from the CSF faster than pyridoxal phosphate, Spector and Johanson (2007) suggested that the phosphorylated form serves as a reservoir. [ 3 H]pyridoxic acid or [ 3 H]pyridoxic acid lactone accounted for less than 10 % of the label in plasma or CSF from in vivo experiments (Spector 1978a) and less than 5 % of the label released from brain and choroid plexus slices from in vitro experiments (Spector 1978b).…”

“…[ 3 H]pyridoxic acid or [ 3 H]pyridoxic acid lactone accounted for less than 10 % of the label in plasma or CSF from in vivo experiments (Spector 1978a) and less than 5 % of the label released from brain and choroid plexus slices from in vitro experiments (Spector 1978b). Spector and Johanson (2007) gave the following data from rabbits: total vitamin B-6 in plasma is 0.30 µmol/L 55 % nonphosphorylated; 0.39 µmol/L in cisternal CSF 26 % nonphosphorylated; 8.9 µmol/kg in brain 23 % nonphosphorylated; brain turnover 17 %/d; CSF turnover 24 %/3 h; permeability-surface area product <10 compared to 0.2 for mannitol (absorbed by simple diffusion) and 158 for leucine (absorbed by facilitated diffusion); Kt * 1-2 µmol/L (half saturation concentration for transport through the blood brain barrier). Spector and Johanson (2007) concluded that since the Kt is similar to plasma concentration the carrier mediated process plays a crucial transport and regulatory role because simple diffusion is relatively unimportant.…”