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Guillermou
Mar 24

Choline is an essential vitamin-like nutrient and methyl donor involved in many physiological processes, including normal metabolism, lipid transport, methylation reactions, and neurotransmitter synthesis.

Choline deficiency causes muscle damage and abnormal fat deposition in the liver, resulting in a condition called non-alcoholic fatty liver disease. Genetic predispositions and gender may influence individual variation in choline requirements and, therefore, susceptibility to choline-induced fatty liver disease.

The recommended adequate intake (AI) of choline is set at 425 milligrams (mg)/day for women and 550 mg/day for men.

Choline is an essential human nutrient that serves several biological functions. It is a source of methyl groups, a precursor for the synthesis of phospholipids, such as phosphatidylcholine and sphingomyelin, and a precursor for the synthesis of the neurotransmitter acetylcholine. Betaine is an osmolyte in addition to its function as a methyl group donor. Homocysteine ​​is converted to methionine by acquiring a methyl group. Folate can donate a methyl group to homocysteine; alternatively, choline is converted to betaine, which can donate a methyl group to homocysteine. Extensive epidemiological research has identified low folate intake as a risk factor for neural tube defects, cardiovascular disease, and several types of cancer. However, epidemiological studies on dietary choline and betaine are few because a food composition database was only recently made available. In a case-control study, higher choline intake was associated with a lower risk of neural tube defects, independent of folate intake.

Choline may also be linked to other diseases, such as neurodegenerative disorders, including Alzheimer's disease, through mechanisms unrelated to methyl group metabolism. Higher betaine intake was also associated with improvements in atherosclerosis and fatty liver.

An elevated plasma concentration of total homocysteine ​​(tHcy) is a risk factor for cardiovascular disease, dementia, Alzheimer's disease, some types of cancer, and mortality. Many studies have found that the intake of folic acid and vitamins B-6 and B-12, nutrients involved in methyl group metabolism, predicts tHcy concentrations. Choline and betaine intake also predict tHcy concentrations. In our study, to evaluate the physiological role of choline intake in a free-ranging population, we analyzed the relationship between choline intake, measured using a food frequency questionnaire (FFQ), and total homocysteine ​​plasma concentrations in participants from the Framingham Offspring Study. Several known determinants of total homocysteine ​​(tHcy), including folic acid, vitamin B-6, alcohol, and caffeine intake, predicted tHcy concentrations in this population.

https://lpi.oregonstate.edu/mic/other-nutrients/choline

https://europepmc.org/article/PMC/2430728

Many "reconstituent" and geriatric products contain choline and/or lecithin (which breaks down into choline and fatty acids during digestion). Cholinergic fibers play a crucial role in cognitive processes, such as learning and memory. Attempts to improve these processes (senile dementia, Alzheimer's) through choline supplementation have only proven successful in very specific cases (in animal studies, a peri- and postnatal supplement improves cognitive processes into adulthood). While it is true that choline is absorbed by the brain via specific transport pathways, its availability at nerve endings is influenced by complex homeostatic mechanisms.

Thus, some choline is incorporated into phospholipids and is only available when needed (enzymatic control). Excess choline is released from the cerebrospinal fluid into the bloodstream via the venous system. Furthermore, cellular uptake of choline in the cholinergic neuron is limited by a low carrier transport constant. The choline precursor, CDP-choline, is currently being studied for the treatment of post-ischemic injuries (efficacy likely due to increased phospholipid synthesis).

Lecithin is an important source of phosphatides, which are naturally found in all cell membranes. Lecithin contains phosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositol, which can provide cell membranes, including brain cell membranes, with the necessary raw materials to maintain healthy structure, function, fluidity, and signaling capacity for proper brain function. As a major component of cell membranes, the phosphatides contained in lecithin function by increasing the cell membrane's phosphatidylcholine/phosphatidylethanolamine to cholesterol ratio. This helps maintain cell membrane structure and increase its fluidity.

Approximately 75% of lipids are phospholipids, lipids that contain phosphorus. In smaller proportions, cholesterol and glycolipids are also present; glycolipids are lipids containing one or more linked monosaccharides. These phospholipids form a lipid bilayer due to their amphipathic nature, meaning they have a hydrophilic head and a hydrophobic tail. The head is composed of a phosphate group of a nitrogenous compound (choline or ethanolamine) and mixes well with water. The tail is composed of fatty acids that repel water. The molecules of the bilayer are oriented such that the hydrophilic heads face the cytosol and extracellular fluid, and the tails face the interior of the membrane.

Phospholipids are the main structural lipids of the eukaryotic membrane, including phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), phosphatidylinositol (PI), phosphatidic acid (PA), and cardiolipin (CL). The composition of the inner and outer lipid layers differs, depending on the presence of proteins that require binding to specific phospholipids.

Glycolipids (5% of membrane lipids) are also amphipathic and are found only in the extracellular portion of the membrane. They are important for maintaining adhesion between cells and tissues and can contribute to cell-cell communication and recognition. They are the target of certain bacterial toxins. One of the most important membrane glycolipids is galactocerebroside, a major component of myelin, the lipid insulation of nerve fibers.

The remaining 20% ​​of membrane lipids consist of cholesterol molecules, which are embedded among the phospholipids on either side of the membrane. Cholesterol molecules confer greater strength to membranes, although they decrease their flexibility. Plant membranes lack cholesterol.

Multiple studies have reported changes in PC content as animals age, with species and tissue specificity. For example, the content of most phosphatidylcholine PCs has been reported to decrease markedly in aged nematodes. Furthermore, overall PC content shows a significant reduction in the kidneys of aged mice, while PC accumulation has been detected in the hippocampus of an aging mouse model. Accordingly, the main mitochondrial PC species are found to increase in the brains of elderly humans. Therefore, the reduction in overall PC content appears to be a general feature of animal aging, except in the aged brain where PC content seems to increase.

Studies in long-lived organisms further support this idea, as overall PC content is higher in multiple tissues of the long-lived naked mole-rat compared to mice. This is also true in humans, as most PC levels are higher in centenarians than in the elderly.

Cardiolipin is a symbolic phospholipid of the mitochondrial membrane. It plays a critical role in many aspects of mitochondrial function: it stabilizes the respiratory chain supercomplex, regulates the activity of mitochondrial membrane proteins, and controls essential mitochondrial signaling pathways. Due to its specialized location, cardiolipin is closely related to respiration, as well as to normal respiratory chain complex function, leading to its association with aging and age-related diseases. Consistently, CL content was found to be decreased in aged nematodes and rodents, while CL content was markedly increased in the adipose tissue of long-lived Ames dwarf mice compared to normal mice, suggesting that increased CL is beneficial for health and longevity. Indeed, a yeast study shows that disruption of CL synthesis leads to decreased longevity. In particular, CL is highly sensitive to oxidative stress, and CL peroxidation can damage the respiratory chain complex, which in turn leads to mitochondrial defects and respiratory dysfunction. In line with this, total chlorophyll (CL) content was found to decrease, while peroxidized CL content increased significantly in the brains of aged rats, which is associated with altered activity of the brain's mitochondrial respiratory complex.

https://www.ncbi.nlm.nih.gov/books/NBK26871/

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https://chem.libretexts.org/Courses/University_of_Kentucky/UK%3A_CHE_103_-_Chemistry_for_Allied_Health_(Soult)/Chapters/Chapter_14%3A_Biological_Molecules/14.3%3A_Phospholipids_in_Cell_Membranes

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https://www.frontiersin.org/articles/10.3389/fphys.2021.775648/full

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