Choline and Acetylcholine

Re:
CHAT (acetylcholine transferase) gene and AD risk

Postby SusanJ » Sun Jun 05, 2016 4:18 pm
Well, a little time in the rabbit hole shows that this is one gene not to ignore, because
acetylcholine, besides dysregulation in AD, also has it's fingerprints at the scene of insulin
and blood glucose control. Sufficient choline/acetylcholine seems to be important beyond
the neural effects. Here you go...
This first study listed was done on human cells, and notes that this effect would be missed
in rat studies because acetylcholine is only a neural signal in rats.
Alpha cells secrete acetylcholine as a non-neuronal paracrine signal priming human beta cell
function
In our model, alpha cells release acetylcholine when activated by lowering glucose concentration to
prime the beta cell response to a subsequent increase in glucose concentration. While additional
paracrine effects of acetylcholine on other cells within the human islet (e.g. delta cells) remain to be
investigated, our results suggest that acetylcholine serves as feed-forward signal to keep the beta cell
responsive to future challenges, thus limiting plasma glucose fluctuations. Moreover, the intracellular
signaling pathways activated by acetylcholine may promote long-term survival of beta cells28. Thus,
this model not only explains how beta cell responses are optimized to counter persistent
physiological fluctuations in blood glucose concentration in humans but it also suggests that
alpha cell-derived acetylcholine acts as a trophic factor to enhance beta cell survival.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3132226/
Also see:
Control of Insulin Secretion by Cholinergic Signaling in the Human Pancreatic Islet
In this study, we demonstrate that the effects acetylcholine produces in the human islet are different
and more complex than expected from studies conducted on cell lines and rodent islets. We found
that endogenous acetylcholine not only stimulates the insulin-secreting β-cell via the muscarinic
acetylcholine receptors M3 and M5, but also the somatostatin-secreting δ-cell via M1 receptors.
Because somatostatin is a strong inhibitor of insulin secretion, we hypothesized that cholinergic input
to the δ-cell indirectly regulates β-cell function. Indeed, when all muscarinic signaling was blocked,
somatostatin secretion decreased and insulin secretion unexpectedly increased, suggesting a reduced
inhibitory input to β-cells. Endogenous cholinergic signaling therefore provides direct stimulatory
and indirect inhibitory input to β-cells to regulate insulin secretion from the human islet.
Why is keeping beta cells running smoothly important?
Insulin release from the pancreatic β-cells must respond acutely to meet the insulin demands of the
organism. However, in type 2 diabetes (T2D) pancreatic β-cells fail to compensate for an increase in
blood glucose concentration with sufficient insulin secretion, leading to progressive hyperglycemia
[1].
(This one also has a good background on beta cells if you want to deep dive.)
And they see choline metabolites as a potential marker for diabetes.
Prospective Associations of Systemic and Urinary Choline Metabolites with Incident Type 2

Diabetes.
In models adjusted for age, sex, and fasting status, plasma betaine was inversely related to new-onset
disease...
http://www.ncbi.nlm.nih.gov/pubmed/26980210
Seems acetylcholine has broader effects than I first thought, and we know AD and Type II
diabetes are related, so perhaps more importantly this is something to certainly target
treatment for those of us with ChAT variants.
Re: CHAT (acetylcholine transferase) gene and AD risk

Postby LG1 » Thu Dec 29, 2016 8:06 pm
rs1880676(A;G) for the CHAT gene here. I ran across an interesting recent NCBI paper.
Here are my notes on that and some notes on supplementing. My notes are geared towards
folks liked myself that don't have a background in biology and/or are newer to the vast body
of Apoe4 info.
Acetylcholine: Acetylcholine is found in the CNS and PNS and is the most common
neurotransmitter.
The Vesicular acetylcholine transporter (VAChT) is a neurotransmitter transporter which is

responsible for loading acetylcholine (ACh) into secretory organelles in neurons making
acetylcholine available for secretion.
Cholinergic nerve is a nerve that releases the neurotransmitter acetylcholine at its synapse.
Apolipoprotein E4 reduces evoked hippocampal acetylcholine release in adult mice.

https://www.ncbi.nlm.nih.gov/pubmed/26526158
“These results demonstrate impairment of the evoked release of acetylcholine in

hippocampus by apoE4 in 12-month-old mice but not in 4-month-old mice…Evoked ACh
release from hippocampal and cortical slices is similar in 4-month-old apoE4 and apoE3
mice but is specifically and significantly reduced in hippocampus, but not cortex, of 12-month-
old apoE4 mice. This effect is accompanied by decreased VAChT levels. These findings show
that the hipocampal cholinergic nerve terminals are specifically affected by apoE4 and that this
effect is age dependent.”
Acetylcholine Supplement?:
https://www.leaf.tv/articles/how-to-inc ... ylcholine/
“Amino acids. Acetyl-N-Carnitine is a kind of amino acid that is able to increase the
production of acetylcholine by donating a small molecule called acetyl (which is made up of
two carbons atoms, three hydrogen ones, and an oxygen atom) to another compound,
which is known as choline. Once choline receives this acetyl molecule, it becomes
acetylcholine (hence the name). Taurine, another amino acid, has been shown to increase
the levels of acetylcholine in the hippocampus, which is a part of the brain. Both amino
acids are readily available as supplements in health stores.”
for me, and him:

can't convert choline to tmg..PEMT gene!!! choline must convert to TMG to be
effective!!!!
choline may not work...the lecithin!!! take: TMG and phosphatidylcholine to get
past those roadblocks.
*****THIS: too much choline gets funnelled into making SAMe giving you
symptoms of toom much methylfolate (which can also result from too much
methylfolate)
....
So the reality for me (and probably Katie) is that extra choline gets pushed into
other parts of choline metabolism, including the path leading to an increase in
acetylcholine. Hence the brain buzz (ACh is all about arousal) and heart
palpitations (a little more complicated to understand, but see
https://courses.washington.edu/chat543/ ... tylch.html which references atrial fibs
- look for "These tractings demonstrate the effects of ACh on supraventricular cells
of the heart...").
TMG is a much better option for the two of us, along with gentle amounts of
choline from the diet, so our bodies can maintain choline equilibrium.
Choline acetyltransferase (commonly abbreviated as ChAT, but sometimes CAT) is

a transferase enzyme responsible for the synthesis of the neurotransmitter
acetylcholine. ChAT catalyzes the transfer of an acetyl group from the coenzyme
acetyl-CoA to choline, yielding acetylcholine (ACh).
The CHAT gene provides instructions for making a protein called choline
acetyltransferase. This protein is located at the ends of nerve cells in specialized
areas called presynaptic terminals. Choline acetyltransferase facilitates the
production of a molecule called acetylcholine.
Acetylcholine is synthesized in certain neurons by the enzyme choline
acetyltransferase from the compounds choline and acetyl-CoA. Cholinergic neurons
are capable of producing ACh. An example of a central cholinergic area is the
nucleus basalis of Meynert in the basal forebrain.

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Re:

CHAT (acetylcholine transferase) gene and AD risk

Why is keeping beta cells running smoothly important?

And they see choline metabolites as a potential marker for diabetes.

Prospective Associations of Systemic and Urinary Choline Metabolites with Incident Type 2

Re: CHAT (acetylcholine transferase) gene and AD risk

The Vesicular acetylcholine transporter (VAChT) is a neurotransmitter transporter which is

Apolipoprotein E4 reduces evoked hippocampal acetylcholine release in adult mice.

“These results demonstrate impairment of the evoked release of acetylcholine in

for me, and him:

Choline acetyltransferase (commonly abbreviated as ChAT, but sometimes CAT) is

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