Functional Expression of Choline Transporters in the Blood–Brain Barrier
"> Figure 1
<p>Schematic illustration of the blood–brain barrier and transporters. The blood–brain barrier is composed of brain microvascular endothelial cells, astrocytes, and pericytes. Diffusion between cells is limited by the mutual binding of brain microvascular endothelial cells by tight junctions. Many of the soluble carrier (SLC) transporters expressed in brain microvascular endothelial cells allow substances, such as nutrients (e.g., glucose, amino acids, peptides, and nucleotides), to selectively cross the blood–brain barrier. In addition, ATP binding cassette (ABC) transporters that are expressed in cerebral microvascular endothelial cells play a role in preventing the entry of toxic substances and drugs into the brain by releasing them into the blood.</p> "> Figure 2
<p>Choline metabolic pathway. Choline is an essential biological molecule for all cells and is required for the synthesis of phosphatidylcholine and sphingomyelin, which are the major components of the plasma membrane. New cell membrane synthesis requires the rate-limiting step of choline uptake, followed by phospholipid biosynthesis. Choline is also a precursor for the neurotransmitter acetylcholine and the methyl donor betaine, which are involved in several important biological functions. Betaine, an oxidized metabolite of choline, is a source of methyl groups for the production of S-adenosylmethionine (SAM), which serves as a substrate for DNA and histone methyltransferases, and is thus required for the establishment and maintenance of the epigenome. Epigenetic mechanisms play important roles in biology and human diseases. ADP, adenosine diphosphate; ATP, adenosine triphosphate; BHMT, betaine-homocysteine methyltransferase; VB12, vitamin B12; CDP, cytidine diphosphate; CK, choline kinase; CMP, cytidine monophosphate; CO, choline oxidase; CPT, choline phosphotransferase; DAG, diacylglycerol; CTP, cytidine triphosphate; methyl-THF, 5-methyltetrahydrofolate; MTHF, 5,10-methylene-tetrahydrofolate; PCP, phosphatidylcholine:ceramide choline phosphotransferase; Pcyt1, CTP:phosphocholine cytidyltransferase; PEMT, phosphatidylethanolamine N-methyltransferase; PLA, phospholipase A2; PPi, pyrophosphate; SAH, S-adenosylhomocysteine; SAM, S-adenosylmethionine; THF, tetrahydrofolate.</p> "> Figure 3
<p>The localization of choline transporters in the blood–brain barrier. CTL1 and CTL2 are expressed in brain microvascular endothelial cells in the blood–brain barrier. Their localization on the luminal side of these cells suggests that they are responsible for the uptake of choline into the brain. CTL2 is also expressed on the apical side of brain microvascular endothelial cells, where choline is excreted into the brain. CTL1 is also expressed in astrocytes, one of the cell types that comprise the blood–brain barrier, and is thought to be linked to phospholipid synthesis. The high-affinity CHT1 and intermediate-affinity CTL1 are functionally expressed in neurons, where they may be involved in the synthesis of acetylcholine and phospholipids, respectively.</p> ">
Abstract
:1. Transport at the Blood–Brain Barrier
2. Role of Choline in the Central Nervous System
3. Characteristics of Choline Transporter Families
4. Functional Expression of Choline Transporters in Human Brain Microvascular Endothelial Cells
5. Potential of CTL1 and CTL2 as Drug Transporters
6. Role of Choline Transporters in the Central Nervous System
Funding
Conflicts of Interest
References
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Protein Name | Km for Choline | Sodium-dependency | Sensitivity of HC-3 (Ki) | Tissue Distribution | Substrates |
---|---|---|---|---|---|
CHT1 | 0.5–3 µM | Yes | 50–100 nM | Brain, spinal cord | Choline |
CTL1 | 10–50 µM | No | 10–100 µM | Multiple tissues | Choline, organic cation |
CTL2 | 50–200 µM | Unknown | Unknown | Placenta, lung | Choline |
CTL3 | Unknown | Unknown | Unknown | Colon, pancreas | Unknown |
CTL4 | Unknown | Unknown | Unknown | Prostate, colon | Thiamine pyrophosphate |
CTL5 | Unknown | Unknown | Unknown | Multiple tissues | Unknown |
OCT1 | 300–400 µM | No | >250 µM | Liver, kidney | Organic cation |
OCT2 | 100–500 µM | No | >250 µM | Kidney, brain | Organic cation |
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Inazu, M. Functional Expression of Choline Transporters in the Blood–Brain Barrier. Nutrients 2019, 11, 2265. https://doi.org/10.3390/nu11102265
Inazu M. Functional Expression of Choline Transporters in the Blood–Brain Barrier. Nutrients. 2019; 11(10):2265. https://doi.org/10.3390/nu11102265
Chicago/Turabian StyleInazu, Masato. 2019. "Functional Expression of Choline Transporters in the Blood–Brain Barrier" Nutrients 11, no. 10: 2265. https://doi.org/10.3390/nu11102265