Big news! l-serine

Medications
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Glycine, N-Methylglycine, N-Acetylcysteine, and NOW L-SERINE!!!

Long story short, L-serine binds to SERINE RACEMASE, an enzyme, and creates D-Serine which binds to NMDA R 1 (NR1), but we need receptors that are NMDA R1/2A so that GABA interneurons can function better and have better, healthier “Synaptic plasticity.” We want the GABA ergic interneurons to be happy healthy content and satisfied so we need NMDA 1/2A receptor “heterodimers” so we need NMDA R1 portion os the protein channel/receptor to stimulate secondary messenger systems which will allow AMPA recruitment to strengthen the synapse.

Another concept is that NMDA R 2A is absent in 50-73% of parvalbumin gaba interneurons. PV appear to balance and/or regulate, scoop up, Ca2+ so the mitochondria do not get overloaded initiating cytochrome c and caspase 3 cascades leading to programmed cell death aka apoptosis.

So how do we get NMDA R2A??? We bind D-Serine into NMDA 1 portion and the 2ndary messenger systems bring about new NMDA R 1/2A heterodimers (Receptor has 4 portions in regards to this: 1/2A/1/2A) so NOW we can have co-agonism of D-SERINE and GLUTAMATE to displace the Mg2+ in the channel and get Ca2+ to go into to cell and eventually down the line transcription of NEW NMDA receptors with NMDA 1/2A. (Glycine is also a coagonist but does not cross the Blood Brain Barrier very good. This is why with 100-fold greater potency, L-serine → serine racemase —> D-serine —> binds to NMDA R 1 with a poor functioning and/or absent 2A portion). The glycine helps bring about more Glutamic Acid Decarboxylase 67 enzymes in the cell).

I currently take 500 mg in the morning, 1000 mg at 5 pm, and 500 mg before bed and there IS A DIFFERENCE PEOPLE.

Comments encouraged, have a good day.

1 Like
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Is that a supplement? I tried them all that were recommended here and most of them made me worse.

The Sarcosine didn’t do anything.

I won’t try anymore. Waste of money.

Unless there is some serious studies behind it I would stay away.

1 Like
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Yes it’s a supplement.

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Great references for the topics discussed.

image

Glycine binds at the glycine site, however, D-serine is 100-fold more potent at the target receptor. Being that glycine does NOT cross the blood brain barrier very good, we see a favorable response with new NMDA receptors that are made with secondary messenger systems, transcription, etc that I will show below:

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This is a game changer right here!!!

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I don’t think L-serine is new. I thought sarcosine was the one that had the strongest impact on nmda receptors?

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But I could give it a shot since sarcosine has been kinda losing its affect on me lately.

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Aren’t they talking about d-serine? I’m just confused.

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How is NMDA receptor activation causing transcription of NMDA receptors?

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Well I ain’t gonna try it.

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I take 1000-1500mg L-serine before bed, seems to help a little with sleep. Supplementing Glutamate and glycine appears to be bad for my sleep though, I think even magnesium glycinate is bad for my sleep. NAC calms me down though.

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Interesting. I’ll ask my pdoc and GP about this.

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Read the document I posted on page 1083 and 1084.

Interestingly, intrareceptor allosteric interactions render the potency of glycine
and d-serine at the GluN1 subunit sensitive to the identity of the
GluN2 subunit (Sheinin et al., 2001; Chen et al., 2008; Dravid et
al., 2010; Jessen et al., 2017; Maolanon et al., 2017). For example,
Figure 2. Subunit stoichiometry and subunit arrangement of GluN1/2
NMDA receptors. The crystal structure of the intact GluN1/2B NMDA receptor (the intracellular CTD omitted from structure; Protein Data Bank accession
no. 4PE5; Karakas and Furukawa, 2014) definitively demonstrated that GluN1
and GluN2 subunits assemble as heterotetramers with an alternating pattern
(i.e., 1-2-1-2). The NMDA receptor is therefore comprised of two glycine-binding GluN1 and two glutamate-binding GluN2 subunits (i.e., GluN1/2 receptors)
that form a central cation-permeable channel pore.
Downloaded from http://rupress.org/jgp/article-pdf/150/8/1081/1235977/jgp_201812032.pdf by guest on 28 January 2023
Hansen et al.
Structure and function of NMDA receptors
Journal of General Physiology
https://doi.org/10.1085/jgp.201812032
1084
the potency of glycine at GluN1/2A receptors is ∼10-fold less than
at GluN1/2D receptors (Chen et al., 2008).
Multiple biophysical properties are also controlled by the
GluN2 subunit. GluN1/2A and GluN1/2B have higher single-channel conductance than GluN1/2C and GluN1/2D receptors (Erreger
et al., 2004; Traynelis et al., 2010; Paoletti et al., 2013; Wyllie et
al., 2013; Glasgow et al., 2015; Fig. 3 C). GluN1/2A and GluN1/2B
also show higher Ca2+ permeability and are more sensitive to
Mg2+ block than GluN1/2C and GluN1/2D (Monyer et al., 1992,
1994; Burnashev et al., 1995; Kuner and Schoepfer, 1996; Qian et
al., 2005; Siegler Retchless et al., 2012). These biophysical differences are important, as the sensitivity to voltage-dependent
Mg2+ block can influence the temporal window for spike timing–
dependent plasticity (Nevian and Sakmann, 2004, 2006; Carter
and Jahr, 2016). Furthermore, the probability that the channel
will be open when all agonist-binding sites are occupied by agonists (i.e., the open probability) is strongly dependent on GluN2
identity (Fig. 3 C). The open probability is ∼0.5 for recombinant GluN1/2A, ∼0.1 for GluN1/2B, and <0.02 for GluN1/2C and
GluN1/2D (Erreger et al., 2004; Traynelis et al., 2010; Paoletti et
al., 2013; Wyllie et al., 2013; Glasgow et al., 2015). The GluN2 subunits also control inhibition of NMDA receptors by endogenous
modulators, such as protons and extracellular Zn2+ (Traynelis et
al., 1995, 1998; Paoletti et al., 1997).
The amino acid sequence of the intracellular CTD is highly
variable among GluN2 subunits, thereby producing pronounced
differences in interaction sites for phosphatases, kinases, and
proteins responsible for anchoring at synaptic sites and surface
trafficking (Wenthold et al., 2003; Traynelis et al., 2010; SanzClemente et al., 2013; Aman et al., 2014; Lussier et al., 2015). As a
result of this variation, the GluN2 subunits therefore influence
cell-surface expression, subcellular localization, and recycling/
degradation of NMDA receptor subtypes.

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You might want to read this article. These NMDA 1/2A/1/2A tetramericheterodimers are on virtually every neuron. This has implications in NMDA, AMPA, Kainate receptors, LTP, LTD, and arc expression in synaptic plasticity.

Just keep an open mind and ill explain if you have questions. Questions and comments welcome.

Diheteromeric and triheteromeric NMDA receptors
The NMDA receptor subunits assemble into receptors with varying composition and distinct functional properties and roles in
the CNS. At least two different GluN2 subunits are expressed in
most neurons, and thus virtually all neurons have the opportunity to signal through triheteromeric NMDA receptors that
contain two GluN1 and two different GluN2 subunits (Chazot et
al., 1994; Sheng et al., 1994; Chazot and Stephenson, 1997; Luo
et al., 1997; Cathala et al., 2000; Piña-Crespo and Gibb, 2002;
Brickley et al., 2003; Jones and Gibb, 2005; Al-Hallaq et al., 2007;
Rauner and Köhr, 2011; Tovar et al., 2013; Huang and Gibb, 2014;
Swanger et al., 2015).

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D-serine is binding to Glu1 during prepore assembly assembly and then the allosteric interactions attract Glu2. Glu2 activation then effects recycling/degradation of NMDA receptor subtypes?

What are your thoughts on the following

Depletion of serine, which is a substrate for glycine production, inhibits proliferation and reduces the level of purine nucleotides in cancer cells [17].

Thus, serine availability, via its extracellular uptake or de novo synthesis, plays a decisive role in controlling the SGOCP’s activity and function (Locasale, 2013; Yang and Vousden, 2016).
The complexity of the serine glycine one-carbon pathway in cancer | Journal of Cell Biology | Rockefeller University Press

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Hey, So I just bought L-Serine. It’s from Bulk Supplements, so hopefully the quality is okay (not too sure about this brand). So anyways, what is the recommended dose? Or does anyone know what the actual dose is for this supplement? I’ve looked into it a bit, and I know L-serine turns into D-serine, but the actual chemistry goes above my head. I also found out it is possible to order D-serine (if you look hard enough online). I will look into getting D-Serine next time. This stuff smells like rotting corpse though, is it supposed to smell like that? The taste isn’t too bad though.

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I came over a study that used 3000mg daily for 12 weeks which went ok. Don’t have the link handy though.

I take 1500mg in the evening. Works well for me.

If you are new to the supplement you should start at low dose and see how you react to it. I would start at 500mg then gradually increase if you feel benefits from taking more.

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ok. I just want a cure right now. I feel my brain deteriorating every day. I want to feel alive again.