It seems like a lot of nootropic interest has historically focused on acetylcholine, probably due to the common brain fog associated with piracetam which is alleviated by supplementing choline. And yet, acetylcholine overload plagues many with symptoms of depression. I have personally found boosting choline serum levels with CDP-Choline and Alpha-GPC too thin of a therapeutic margin to consider an effective supplement. What else could be taken to receive the same benefits as choline supplementation without the tight-rope act?
Below is the CDP-choline cycle, which is the cellular process that converts choline to acetylcholine. As you can see, there is another pathway from choline that leads to phospholipid synthesis. I propose that many of the pro-cognitive effects arising from boosting choline levels can be attributed not only to increased acetylcholine levels, but also increased rate of phospholipid synthesis. This is evidenced by the efficacy of drugs involved with the CDP-choline cycle such as ALCAR, uridine, phosphatidylserine, and glycerophosphate (contained in alpha-GPC), which do not directly add choline to the brain.
Can these intermediates in choline metabolism be used in place of choline itself for most nootropic purposes? I am going to try using phosphatidylserine in place of CDP-choline. I may also add uridine. I already take ALCAR, which apparently can contribute the acetyl group to acetylcholine synthesis.
And as choline is considered a dietary nutrient, I assume an actual source of choline should still be consumed (in a small quantity) if not already sourced dietarily.
Phosphatidylcholine and the CDP-choline cycle.
http://www.ncbi.nlm....2404/figure/F2/
Biochemical relationships between the CDP-choline pathway of PtdCho synthesis, the degradation of PtdCho, and general phospholipid metabolism in mammals. Choline uptake is mediated by the organic cation transporters (OCTs) which rely on facilitated diffusion governed by the choline concentration gradient and the electrical potential across the membrane. Active transport of choline is mediated by the choline transporter-like proteins (CTLs) that are energized by adenosine triphosphate (ATP) hydrolysis. The high-affinity choline transporters (CHTs) are Na+-dependent and require ATP hydrolysis. Intracellular choline can be acted upon by three different enzymes: the choline dehydrogenase (CHDH), choline acetyltransferase (CAT) and choline kinase (CK). CHDH is localized inside the mitochondria and oxidizes choline to betaine aldehyde, with oxygen being the final electron acceptor. The betaine aldehyde is oxidized to betaine by the betaine aldehyde dehydrogenase (BADH) in concert with the conversion of oxidized nicotinamide adenine nucleotide (NAD+) into the reduced nicotinamide adenine nucleotide (NADH). Choline acetylation is catalyzed by the choline acetyltransferase (CAT) that transfers the acetyl group from acetyl-coenzyme A (AcCoA) to choline, yielding free coenzyme A (CoA) and acetylcholine. CK catalyzes the esterification of the choline hydroxyl group with the γ-phosphate of the ATP to produce phosphocholine (P-choline) plus adenosine diphosphate (ADP). The phosphocholine cytidylyltransferase (CCT) uses cytidine triphosphate (CTP) to convert P-choline into CDP-choline, with the release of pyrophosphate (PPi). The CDP-choline is esterified with diacylglycerol (DAG) by the cholinephosphotransferase (CPT) or the choline/ethanolaminephosphotransferase (CEPT) to produce 1,2-diacyl-glycerophosphocholine (PtdCho) and cytidine monophosphate (CMP). The Legionella pneumophila-encoded AnkX(Lp) can hijack CDP-choline to esterify a serine hydroxyl group of Rab1 protein. PtdCho can be hydrolyzed into choline and phosphatidic acid (PtdOH) by phospholipase D (PLD); in turn, PtdOH can be hydrolyzed into DAG and Pi. PtdCho can also be hydrolyzed into DAG and P-choline by phospholipase C (PLC). Neuropathy target esterase (NTE) hydrolyzes the two acyl chains (FA) of PtdCho to yield glycerophosphocholine (GroPCho), which can then be further hydrolyzed into glycerophosphate (GroP) and choline by the glycerophosphodiesterase (GPD). Phosphatidylserine synthase 1 (PSS1) catalyzes a base-exchange reaction with PtdCho substituting the choline group with serine (Ser) to produce phosphatidylserine (PtdSer). The sphingomyeline synthase (SMS) substitutes DAG for ceramide (Cer) to yield sphingomyelin (Sph). Sph can be hydrolyzed into P-choline and Cer by sphingomyelinase (SMase). Phospholipases A (PLA) can degrade PtdCho to yield lysophosphatidylcholine (lyso-PtdCho) and further hydrolysis of lyso-PtdCho yields GroPCho. The free hydroxyl group in lyso-PtdCho can be esterified by the acylglycerophosphate acyltransferase (AGPAT) using acylCoA as the donor of the acyl-group to yield PtdCho.
Edited by Fenix_, 21 October 2014 - 01:09 AM.
