Phosphatidylcholine and sphingomyelin, two important components of cell membranes in vitro, are precursors to choline [3]. Through its metabolite betaine, which is involved in the S-adenosylmethionine synthesis pathway, choline serves as the primary source of methyl groups as well [4].

Use oral gavage to provide choline bitartrate (300 mg/kg as opposed to 5 g/kg). Mice on choline restriction (300 mg/kg) had significant hepatic steatosis, inflammation, and cell damage in addition to a robust ketosis and weight loss. Moderate ketosis and the build-up of liver fat can be minimized when choline levels are adequate [4].

Absorption, Distribution and Excretion
Choline is absorbed from diet as such or as lecithin. Latter is hydrolyzed by intestinal mucosa to glycerophosphoryl choline, which either passes to liver to liberate choline or to peripheral tissues via intestinal lymphatics. /Choline/
Choline are absorbed via the portal circulation ... The liver takes up the majority of choline and stores it in the form of phosphatidylcholine and sphingomyelin. Kidney and brain also accumulate choline ... Some free choline is excreted with urine ... A specific carrier is needed for the transport of free choline across the blood-brain barrier, and the capacity is especially high in neonates. /Choline/
Free choline is transported across the blood-brain barrier at a rate that is proportional to serum choline level ... In advanced age ... brain choline uptake /is decr/ ... /Choline/
During pregnancy, large amt of choline are delivered to the fetus across the placenta and this depletes maternal stores. Choline concn in amniotic fluid is 10-fold greater than that in maternal blood. At birth, humans and other mammals have plasma choline concn that are much higher than those in adults ... In rats, the liver choline concn in late pregnancy decr to less than one-third that of nonpregnant females ... /Choline/
For more Absorption, Distribution and Excretion (Complete) data for CHOLINE BITARTRATE (8 total), please visit the HSDB record page.

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Metabolism / Metabolites
Free choline is not fully absorbed, especially after large doses, and intestinal bacteria metabolize choline to trimethylamine. /Choline/
/The/ ability to form choline /de novo via the methylation of phosphatidylethanolamine using S-adenosylmethionine as the methyl donor, mostly in the liver,/ means that some of the demand for choline can ... be met using methyl groups derived from 1-carbon metabolism (via methyl-folate and methionine). Several vitamins (folate, vitamin B12, vitamin B6, and riboflavin) and the amino acid methionine interact with choline in 1-carbon metabolism ... Methionine, methyl-tetrahydrofolate (THF), and choline can be fungible sources of methyl groups. /Choline/
Before choline can be absorbed in the gut, some is metabolized by bacteria to form betaine and methylamines (which are not methyl donors) ... Although some free choline is excreted with urine, most is oxidized in the kidney to form betaine ... /Choline/
Acetylcholine is one of the most important neurotransmitters used by neurons in the memory centers of the brain (hippocampus and septum). Choline accelerates the synth and release of acetylcholine in nerve cells. Choline used by brain neurons is largely derived from membrane lecithin /(phosphatidylcholine)/, or from dietary intake of choline and lecithin ... Choline derived from lecithin may be especially important when extracellular choline is in short supply, as might be expected to occur in advanced age because of decr brain choline uptake ... /Choline/
For more Metabolism/Metabolites (Complete) data for CHOLINE BITARTRATE (6 total), please visit the HSDB record page.

Interactions
Methotrexate may diminish pools of all choline metabolites. Choline supplementation reverses fatty liver caused by methotrexate admin in rats. /Choline/
Repeated admin of choline chloride to female rats incr liver necrosis caused by carbon tetrachloride.
This study was designed to examine the biochemical and embryotoxic interaction of excessive dietary vitamin A and deficiency of methylation pathway constituents, namely absence of folate and choline and a reduction of methionine. Simonsen albino rats were maintained for 36 days on a diet with either normal (4 IU per gram of diet) or excessive retinyl palmitate (RP) (100 or 1000 IU per gram of diet), and normal (2 ug folic acid, 5 mg methionine and 4.2 mg choline bitartrate per gram of diet) or absence of the three dietary factors. CD-1 mouse embryos were exposed to the diet from gestational day 0 to 8, and rat serum from day 8 to 10 during whole embryo culture. The high dose of RP induced 55.4% open anterior neuropores when methylation pathway constituents were included in the diet, but this same retinoid level produced only 12.5% embryos with this defect when these constituents were omitted. Acidic retinoid levels were low in serum (less than 5 ng/mL) via HPLC. Measurements of selected methylation and transsulfuration pathway components did not yield differences in these biochemical intermediates. Thus, dietary folate, choline and methionine facilitate the induction of retinoid-induced neural tube defects.

[1]. An introduction to the nutrition and metabolism of choline. Cent Nerv Syst Agents Med Chem. 2012 Jun;12(2):100-13.

[2]. Choline metabolism provides novel insights into nonalcoholic fatty liver disease and its progression. Curr Opin Gastroenterol. 2012 Mar;28(2):159-65.

[3]. Development of a chemically defined platform fed-batch culture media for monoclonal antibody-producing CHO cell lines with optimized choline content. Cytotechnology. 2018 Jun;70(3):939-948.

[4]. Role of choline deficiency in the Fatty liver phenotype of mice fed a low protein, very low carbohydrate ketogenic diet. PLoS One. 2013 Aug 29;8(8):e74806.

A basic constituent of lecithin that is found in many plants and animal organs. It is important as a precursor of acetylcholine, as a methyl donor in various metabolic processes, and in lipid metabolism.

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Mechanism of Action
Several mechanisms are suggested for the cancer-promoting effect of a choline-devoid diet. These incl incr cell proliferation related to regeneration after parenchymal cell death occurs in the choline deficient liver, hypomethylation of DNA (alters expression of genes), reactive oxygen species leakage from mitochondria with incr lipid peroxidation in liver, activation of protein kinase C signaling due to accumulation of diacylglycerol in liver, mutation of the fragile histidine triad (FHIT) gene, which is a tumor suppressor gene, and defective cell-suicide (apoptosis) mechanisms. Loss of phposphatidylethanolamine N-methyl-transferase (PEMT) function may also contribute to malignant transformation of hepatocytes. /Choline/
Acetylcholine is one of the most important neurotransmitters used by neurons in the memory centers of the brain (hippocampus and septum). Choline accelerates the synth and release of acetylcholine in nerve cells. /Choline/
... Choline deficiency in cell culture causes apoptosis or programmed cell death. This appears to be due to abnormalities in cell membrane phosphatidylcholine content and an incr in ceramide, a precursor, as well as a metabolite of sphingomyelin. Ceramide accumulation, which is caused by choline deficiency, appears to activate a caspase, a type of enzyme that mediates apoptosis. /Choline/

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Therapeutic Uses
Some clinical improvement with choline treatment has also been reported in huntington's chorea...in gilles de la tourette's disease, in friedreich's ataxia, & in presenile dementia ... /Choline/
A nutrient and/or dietary supplement food additive
/EXPL THER/ Eight lithium-treated patients with DSM-IV bipolar disorder, rapid cycling type were randomly assigned to 50 mg/kg/day of choline bitartrate or placebo for 12 weeks. Brain purine, choline and lithium levels were assessed using 1H- and 7Li-MRS. Patients received four to six MRS scans, at baseline and weeks 2, 3, 5, 8, 10 and 12 of treatment (n = 40 scans). Patients were assessed using the Clinical Global Impression Scale (CGIS), the Young Mania Rating Scale (YRMS) and the Hamilton Depression Rating Scale (HDRS) at each MRS scan. ... There were no significant differences in change-from-baseline measures of CGIS, YMRS, and HDRS, brain choline/creatine ratios, and brain lithium levels over a 12-week assessment period between the choline and placebo groups or within each group. However, the choline treatment group showed a significant decrease in purine metabolite ratios from baseline (purine/n-acetyl aspartate: coef = -0.08, z = -2.17, df = 22, p = 0.030; purine/choline: coef = -0.12, z = -1.97, df = 22, p = 0.049) compared to the placebo group, controlling for brain lithium level changes. Brain lithium level change was not a significant predictor of purine ratios. ... The current study reports that oral choline supplementation resulted in a significant decrease in brain purine levels over a 12-week treatment period in lithium-treated patients with DSM-IV bipolar disorder, rapid-cycling type, which may be related to the anti-manic effects of adjuvant choline. This result is consistent with mitochondrial dysfunction in bipolar disorder inadequately meeting the demand for increased ATP production as exogenous oral choline administration increases membrane phospholipid synthesis.
/EXPL THER/ ... Choline bitartrate was given openly to 6 consecutive lithium-treated outpatients with rapid-cycling bipolar disorder. Five patients also underwent brain proton magnetic resonance spectroscopy. Five of 6 rapid-cycling patients had a substantial reduction in manic symptoms, and 4 patients had a marked reduction in all mood symptoms during choline therapy. The patients who responded to choline all exhibited a substantial rise in the basal ganglia concentration of choline-containing compounds. Choline was well tolerated in all cases. Choline, in the presence of lithium, was a safe and effective treatment for 4 of 6 rapid-cycling patients in our series. A hypothesis is suggested to explain both lithium refractoriness in patients with bipolar disorder and the action of choline in mania, which involves the interaction between phosphatidylinositol and phosphatidylcholine second-messenger systems.
For more Therapeutic Uses (Complete) data for CHOLINE BITARTRATE (6 total), please visit the HSDB record page.

C9H19NO7

253.2497

253.116

87-67-2

Choline chloride;67-48-1;Choline theophyllinate;4499-40-5

6900

White to off-white solid powder

1.47 g/cm3

399.3ºC at 760 mmHg

151-153°C

209.4ºC

4

7

4

17

193

2

C[N+](C)(C)CCO.[C@@H]([C@H](C(=O)[O-])O)(C(=O)O)O

QWJSAWXRUVVRLH-LREBCSMRSA-M

InChI=1S/C5H14NO.C4H6O6/c1-6(2,3)4-5-7;5-1(3(7)8)2(6)4(9)10/h7H,4-5H2,1-3H3;1-2,5-6H,(H,7,8)(H,9,10)/q+1;/p-1/t;1-,2-/m.1/s1

2-hydroxyethyl(trimethyl)azanium;(2R,3R)-2,3,4-trihydroxy-4-oxobutanoate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O : ~120 mg/mL (~473.84 mM)
DMSO : ~55 mg/mL (~217.18 mM)

Solubility in Formulation 1: ≥ 2.75 mg/mL (10.86 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 27.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.75 mg/mL (10.86 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 27.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.75 mg/mL (10.86 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 27.5 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 100 mg/mL (394.87 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)