The Clinical Use of Phosphatidylcholine
Phosphatidylcholine (PC) is a phospholipid integral to maintaining the structure and fluidity of a cell membrane. Additionally, PC provides structure to circulating lipoproteins and is essential for lipid transport and metabolism.1 PC is as an essential component of bile, facilitating fat emulsification, absorption and transport and is an important constituent of surfactants in the body, including those of the lungs and gastrointestinal tract, offering protection to epithelial-luminal interfaces.2
The abundance of PC within cellular membrane bilayers and organelles, and the intercellular variability in PC concentrations between different cell types, is representative of its physiological importance in the body.3,4 Comprising 40-50% of total cellular phospholipids, the clinical significance of PC’s physiological presence is highlighted by ongoing research into links between endogenous PC levels and its mechanistic functions, with pathologies involving several body organs and systems.4
What is Phosphatidylcholine?
Composed of two hydrophobic fatty acyl chains and a glycerol hydrophobic head, phospholipids are found in cellular membranes, offering structural support to the cell.3 Phosphatidylcholine is a phospholipid with a phosphate group joined to a molecule of choline at the hydrophobic head, differentiating it from other phospholipids.4 (See Fig. 1)
Sometimes referred to as lecithin although technically different, PC is in fact a component of lecithin.5 Acetylcholine, essential for memory, is produced by the body from phosphatidylcholine.5
Phosphatidylcholine synthesis
The autogenous synthesis of PC is complex, occurring via the CDP-choline pathway (also known as the Kennedy pathway), phosphatidylethanolamine N-methyltransferase (PEMT) and Lands cycle pathways. (See Fig. 2)3,4,7,8
The CDP-choline Pathway
The CDP-choline pathway, expressed by all human nucleated cells, is the main source of de novo PC synthesis.3,4,7,8 The CDP-choline pathway involves the phosphorylation of choline by ATP to phosphocholine with the assistance of choline kinase found in the cytosol.3 CTP and phosphocholine are then converted via several enzymatic processes to produce CDP-choline and diacylglycerol (DAG), generating PC.3
The PEMT Pathway
The PEMT pathway contributes a substantially smaller proportion of endogenous PC, expressed primarily in hepatic tissues, with small amounts expressed in adipose tissue.3,4,7,8 The PEMT pathway involves phosphatidylethanolamine (PE) undergoing three methylation reactions in a sequence with the methyl group donor being S-adenosylmethionine and the enzyme phosphatidylethanolamine N-methyltransferase (PEMT), producing PC.3
The Lands Cycle
The Lands cycle further emphasises the complexity of PC synthesis and its functional/biological effects, involving the remodelling of PC into subspecies (LPCATs 1-4) that are differentially distributed in body tissues including lung alveolar, immune, brain, hepatic, intestinal, adipose, and ovarian cells.8,9
Phosphatidylcholine physiological mechanisms
Current research regarding PC’s physiological mechanisms demonstrates its significant involvement in many central nervous system, mitochondrial, hepatic, intestinal, respiratory, and metabolic processes.3,10 Such mechanisms form the foundational basis for the clinical use and application of PC in a range of pathologies pertaining to these tissues, organs and systems as a consequence of imbalanced endogenous levels. (See Table 1)
Exogenous sources of Phosphatidylcholine
PC is available in both dietary and supplemental form, with concentrated food sources being primarily eggs, meat, fish, milk, and soy products as well as being present in smaller concentrations in potatoes and leafy greens.36-38
Several factors need to be considered when reviewing the suitability of obtaining appropriate quantities of PC from food sources alone versus supplemental sources. These factors include:
- An individuals’ normal dietary patterns, with vegetarian, vegan and low-carbohydrate diets associated with lower endogenous levels;
- Life stage (pregnancy, lactating and growth phases may increase need); and
- The presence of physiological imbalances or pathologies associated with suboptimal PC metabolism and levels (Table 1).38-40
Another significant consideration observed in a recent animal study demonstrating that compared with dietary PC intake, supplemental PC did not increase plasma levels of trimethylamine-N-oxide (TMAO), elevated levels of which are associated with adverse effects on humans in relation to colorectal cancer, cardiovascular, and kidney health.41 Further, it has been reported that as a primary source of choline, PC is absorbed more effectively compared with free choline due to reduced catabolism by the gastrointestinal microbiome.41
Physiological role of Phosphatidylcholine
Research is ongoing regarding the physiological relevance of PC and its subspecies in human health and disease. The importance of appropriate intake levels of PC to maintain normal physiological function and the impact of impaired or dysregulated metabolism and subsequent PC levels and functional effects may have in many clinical conditions have been established. Insufficient PC levels or changes to the cellular ratio of PC:PE may alter organelle energy metabolism within the cell, disrupting the function of the cell.3
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