Phosphatidylcholine highly present in the membranes of mitochondria,

Phosphatidylcholine (PC): Phosphatidylcholine
is a quaternary amine (2-hydroxyethyl-N, N, N-trimethylammonium) present in
food as well as milk in both free and esterified forms. The main forms present
in foods are phosphatidylcholine, lecithin, These are also present as animal
tissues, free choline, phosphocholine (PChol), glycerophosphocholine (GPC) and
sphingomyelin (SPM), and minor amounts of cytidine-5-diphosphate-choline
(CDP-choline) and acetylcholine. 1,2

Choline, PChol and GPC are water-soluble choline
compounds, while PC and SPM are soluble in lipids. Choline can also be
synthesised de novo by the human body but this synthesis may become
insufficient, making choline an important part of human diet. Choline is
predominantly provided via the diet. The human body can also use de novo
synthesis like methylation of phosphatidylethanolamine (PE) from the hepatic
phosphatidylethanolamine N-methyltransferase (PEMT) pathway, or by hydrolysis
of PC formed in the CDP-choline pathway in all cells of the body to form
choline. The PC formed in the PEMT pathway contains substantial amounts of
long-chain polyunsaturated fatty acids, like docosahexaenoic acid and
arachidonic acid. These fatty acids are very important to the development of
the human brain. 3

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Phosphatidylethanolamine (PE): Phosphatidylethanolamine contributes to about 20-30% of total phospholipid content and is the
second most abundant phospholipid in membranes of mammals. PE has two important
characteristics that include 1.  PE
consists of a relatively small head group, thus it can accommodate the
insertion of proteins within the membrane while still maintaining the integrity
of membrane. 2. PE has a propensity to form a non-bilayer structure, which helps
in formation of new membranes and vesicles, and also membrane fusion and
budding process. 4, 5 PE is also highly present in the membranes of mitochondria, being an
essential molecule for growth and stability of these energy-producing
organelles. PE is used in the production of glycosylphosphatidylinositol, which
facilitates the anchoring of proteins to the membrane. 6

Further consists two
types of lipids majorly, 1. Phosphatidylethanolamine or cephalin is one type of
a lipid which is found organic and natural membranes. Phosphatidylethanolamine
also occurs in play tissues and even mammals however in fewer amounts. It is
actually synthesized by the inclusion of diglyceride to CDP-ethanolamine which
releases CMP. Cephalin is a lipid derivative and normally originates in living
cells even though human physiology it originates especially in the nervous
tissues like neural tissue, nerves, white matter in brain and in the spinal
cord. 7 2. Lecithin is one type of phosphatidylethanolamine which
contains a mixture of glycerol etherified along with phosphoric acid and two
fatty acids. However, the group of phosphate is combined with choline in the
phosphatidylethanolamine called Lecithin.


Phosphatidylinositol (PI): PI
constitutes to around 10% of phospholipids in a cell or tissue. Inositol is a cyclohexane derivative wherein all 6 carbons
are substituted by hydroxyl groups. The most common isoform of Phosphatidylinositol is myo-inositol. Their lipid composition in
the mammalian (inositol phospholipids) PIPn carry stearic and arachidonic acid
esters at the glycerol sn-1 and sn-2-positions, respectively. 8


Phosphatidylserine (PS): Phosphatidylserine (PS) is the major anionic
phospholipid class that is enriched in the inner leaflet of the plasma membrane
of the neural tissues. PS is synthesized from phosphatidylcholine or
phosphatidylethanolamine by exchanging the base head group with serine in
reactions are catalyzed by phosphatidylserine synthase 1 and phosphatidylserine
synthase 2 located in the endoplasmic reticulum. Activation of, mitocondrial
Raf-1 and protein kinase C signaling, This supports neuronal survival and
differentiation, necessiating interaction of these proteins with PS localized
in the cytoplasmic leaflet of the plasma membrane.9


Bioavailability (ADME) / Pharmacokinetics:


Phosphatidylcholine (PC): Since
Phosphatidylcholine is a charged hydrophilic cation, it needs transport
mechanisms to cross biological membranes. Three transport mechanisms are known
1. Sodium and chloride dependent high affinity mechanism 2.A sodium-independent
low-affinity carrier-mediated saturable mechanism in all tissues 3.A
sodium–independent saturable uptake mechanism 
Free choline is transported in the aqueous phase of plasma, whereas
phosphorylated choline compounds i.e. PC, PChol, GPC, SPM are associated with
or are part of lipoproteins. 10


In new-born’s, serum free choline
concentrations were significantly higher i.e. > twice maternal values and
phospholipid-bound choline concentrations were significantly lower by about 40%
than in their mothers 11. Phospholipid-bound choline plasma concentrations in
the infants are observed to increase by 893 by 40% starting from day 5–15 after
birth to reaching age of about ten years. Plasma free choline concentration of new-borns
remained high for two weeks after birth, was observed to be slightly higher
than adult levels at the age of two years and remained stable at around10
µmol/L at the age 3-12 years. This high new-born’s plasma concentration
possibly reflects the increase of choline. But there was no correlation between
maternal and new-borns plasma phospholipid-bound choline 12, 13  


Phosphatidylethanolamine(PE): Studies
indicate that Erythrocyte
phosphatidylethanolamine and phosphatidylcholine in infants fed human milk have
20 to 22 carbon polyunsaturated fatty acids  that are higher than infants consuming only
vegetable fat. 14    


Phosphatidylinositol (PI): In
new-borns which are considered to be healthy there is a negative correlation
between lung effluent phosphatidylglycerol and serum myoinositol, wherein r = –
0.968, and a positive linear correlation between myoinositol and lung effluent
phosphatidylinositol, r = 0.849. 15


Phosphatidylserine (PS): Phosphatidylserine is obtained by uptake from the cerebral circulation
or by glucose synthesis. The serine concentration in normal human plasma is 11.2
mg/L, these accounts for 3% of the total plasma free amino acid content 16.

Three Na+
dependent neutral amino acid transporters that are present on the abluminal
surface of the capillary endothelium are used to transport Phosphatidylserine across the blood brain barrier by 17.


Factors that influence and modulate
digestion, absorption and metabolism:


Phosphatidylcholine (PC): Sodium
and chloride dependent high-affinity carrier-mediated saturable uptake system
in presynaptic cholinergic nerve terminals are linked to acetylcholine
synthesis 18. The transporter is the high-affinity choline transporter which
is a solute carrier that needs adenosine triphosphate hydrolysis. Further,
disturbing the cell membrane can reduce choline availability for acetylcholine
synthesis and eliminate cholinergic transmission in the body. These are
important for metabolism and transportation of Phosphatidylcholine 19.


Sodium independent low-affinity carrier
mediated saturable mechanism in all tissues. This mechanism is based on hydrolysis,
with an average affinity for choline to be > 20–200 µM. 20. This mechanism
can take place in enterocytes, hepatocytes, kidneys, placental tissue,
mitochondria, and synaptosomes, and supplies choline for the synthesis of PC
and SPM as well as of betaine. This type of uptake for Phosphatidylcholine is
stereospecific and can be inhibited by similar nitrogen-methyl compounds.


Sodium–independent saturable uptake
mechanism for Phosphatidylcholine is for choline to cross the blood-brain barrier
and erythrocyte membranes by facilitated diffusion. This is a high affinity
mechanism 21




Phosphatidylethanolamine (PE):  The CDP-ethanolamine pathway consists of three enzymatic steps.
ATP-dependent phosphorylation of ethanolamine by ethanolamine kinase to form
phosphoethanolamine with Adenosine diphosphate (ADP) released as a byproduct is the first step 14. 
The second step of the CDP-ethanolamine pathway, which is considered to
be rate-limiting, is catalyzed by the protein, and CTP:phosphoethanolamine
cytidylyltransferase 22 .Final step of PE synthesis by the CDP-ethanolamine
pathway, 1,2-diacylglycerol ethanolamine phosphotransferase utilizes the energy
provided by CDP-ethanolamine to attach ethanolamine to the membrane-embedded
diacylglycerol (DAG) thus forming PE 14, 23, 24.


Further in another research conducted by Riekhof
and Voelker wherein acylation of Lyso- Phosphatidylethanolamine and head Group Exchange these two forms of Phosphatidylethanolamine synthesis are considered minor pathways
of Phosphatidylethanolamine production.
Lyso- Phosphatidylethanolamine is brought in through the exogenous
lysophospholipid metabolism pathway. This pathway can utilize dietary lyso- Phosphatidylethanolamine that is first translocated across the plasma
membrane and then acylated 25.


Phosphatidylinositol (PI): Investigation of Phosphoinositide metabolism in
Synaptojanin 1–deficient mice correlated with increased steady-state levels of
specific phosphoinositides in living cells.  cortical neurons in primary culture after 10
days in vitro were metabolically labeled with 3Hinositol for 48
hr. Lipid extraction followed by HPLC analysis revealed a selective increase of
1.6-fold, p


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