From: Kofi on
OCTN2 is upregulated by intermittent fasting, exercise, PPARalpha
agonists and, I think, testosterone. It's vital for carnitine uptake
(which is antiinflammatory in the gut) and butyrate metabolism (crucial
for HDAC inhibition).

Drug Metab Dispos. 2009 Jun 1;

Changes in mRNA expression levels of solute carrier transporters in
inflammatory bowel disease patients.
Wojtal KA, Eloranta JJ, Hruz P, Gutmann H, Drewe J, Beglinger C, Fried
M, Kullak-Ublick GA, Vavricka SR.
University Hospital Zurich.

Inflammatory bowel disease (IBD) is an inflammatory condition that
affects gastrointestinal tract. Solute carrier superfamilly of
transporters (SLC) comprise proteins involved in the uptake of drugs,
hormones, and other biologically active compounds. The purpose of this
study was to determine the mRNA expression levels of 15 solute carrier
transporters in two regions of the intestine in IBD patients. Endoscopic
biopsies were taken from two locations (terminal ileum and colon) for
histological examination and RNA extraction. We quantitatively measured
the mRNA expression of 15 SLC transporters in 107 IBD patients (53
Crohn's disease and 54 ulcerative colitis) and 23 control subjects.
Messenger RNA expression was evaluated using the quantitative reverse
transciption-PCR technique. We observed that in ileum of IBD patients,
mRNA levels for SERT, ENT1, ENT2, and OATP2B1 were significantly
elevated while for ASBT and OCTN2 they were significantly lower. In
colon, mRNA levels for ENT1, ENT2, CNT2, OATP2B1, and OATP4A1 were
significantly higher, while mRNA levels for OCTN2 were significantly
decreased. In inflamed colon of IBD patients the mRNA expression levels
of ENT1, ENT2, CNT2, OATP2B1, OATP4A1, and PEPT1 were significantly
higher. We conclude that intestinal SLC mRNA levels are dysregulated in
IBD patients, which may be linked to the inflammation of the tissue and
provides an indication about the role of inflammatory signalling in
regulation of SLC expression.

PMID: 19487253
From: jay on
> OCTN2 is upregulated by intermittent fasting, exercise, PPARalpha
> agonists and, I think, testosterone.  It's vital for carnitine uptake
> (which is antiinflammatory in the gut) and butyrate metabolism (crucial
> for HDAC inhibition).
>  
> Changes in mRNA expression levels of solute carrier transporters in
> inflammatory bowel disease patients...

Does the study distinguish if OCTN2 (carnitine transporter) reduction
causes IBD or that OCTN2 is simply reduced during inflammation? Since
carnitine is an antioxidant and is essential for metabolism of long
chain fatty acids (LCFAs), lack of it could cause inflammation. On the
other hand, during inflammation, cell many not want to metabolize
LCFAs since they are prone to peroxidation.
From: Kofi on
In article
<edd2ecbf-aa30-45c8-84fe-d0af1852234c(a)p20g2000vbl.googlegroups.com>,
jay <jaym1212(a)hotmail.com> wrote:

> > OCTN2 is upregulated by intermittent fasting, exercise, PPARalpha
> > agonists and, I think, testosterone. �It's vital for carnitine uptake
> > (which is antiinflammatory in the gut) and butyrate metabolism (crucial
> > for HDAC inhibition).
> > �
> > Changes in mRNA expression levels of solute carrier transporters in
> > inflammatory bowel disease patients...
>
> Does the study distinguish if OCTN2 (carnitine transporter) reduction
> causes IBD or that OCTN2 is simply reduced during inflammation?

Given that supplemental carnitine in liposomes has alleviated TNBS
colitis in mice when TNBS downregulates OCTN2, I'd say it's causative
[PMID 17065219]. The other limiting factor might be glutamine (via the
Atb0+ transporter).

> Since
> carnitine is an antioxidant and is essential for metabolism of long
> chain fatty acids (LCFAs), lack of it could cause inflammation. On the
> other hand, during inflammation, cell many not want to metabolize
> LCFAs since they are prone to peroxidation
From: jay on
> Given that supplemental carnitine in liposomes has alleviated TNBS
colitis in mice when TNBS downregulates OCTN2, I'd say it's causative
[PMID 17065219]. The other limiting factor might be glutamine (via
the
Atb0+ transporter).

Thanks, I'll try glutamine next for the burning tongue syndrome that I
have been experiencing for the last 8 years. In the last two years it
has reduced mostly by avoiding trigger foods of which there are many
including organic fruits and veggies.

Per your advice, I recently added carnitine and alpha lipoic acid
(ALA) and they both reduce the tongue burn. And of the two, ALA seems
to be more effective. It also seems my "food allergies" which manifest
itself as itching, sharp intermittent shooting pains and hand
numbness have been reduced, at least for black pepper and raw
hazelnuts. And I can ingest more beans before incurring a heartburn.

But I am wondering if I have the OCTN1 vs OCTN2 defect which would
prevent the plant derived antioxidant, ergothioniene, from being
accumulated in related tissues (ie skin, gut, endothelial lining,
eyes, joints, immune cells, nervous system). OCTN1 variants are also
linked to CD, RA, lupus, psoriasis and leukemia.

Recent I experimented with cooked vs raw bananas and strawberries. For
some reason cooked cause less tongue burn than raw ones. Anyone else
experience this? What might be the reason?

Have you noticed that an apple or potato turns brown when cut or
bruised. Supposedly, the enzyme tyrosinase converts some polyphenols
into quinones. Quinones are quite reactive and apparently have anti-
viral, bacterial, insect and worm properties.

In humans, a similar process is used to produce melanin. Here tyrosine
is oxidized by tyrosinase into quinones and then further into melanin.
Supposedly ingested dietary polyphenols are also oxidized into
quinones. And neurotransmitters (ie adrenaline) are also oxidized into
quinones. Coincedentally, I get bloating and nerve pain from elevated
stress. And according to some abstracts, vitiligo (white skin) may be
related to quinones also.

Does anyone have links that describe the metabolism of dietary
polyphenols and if it involves carnitine or ergothioniene? Also can
anyone suggest some low molecular weight, non-phenolic based,
antioxidants effective against quinones and hydrogen peroxide (H2O2)?
Thx

Background Info: Various members in my family have suffered Crohn's
Disease, Psoriasis, Dermatitis, Breast Cancer, Leukemia, Cataracts,
etc. Starting 2001, I also experienced gut inflammation, rhoids/
fissures, pain near terminal ileum, IBS, CFS, neuropathy, CTS, RLS,
sciatica, heartburns, sore joints and food allergies that peaked in
late 2007. About half a year ago I starting developing vitiligo on my
hands.

---------
Catechin metabolism: glutathione conjugate formation catalyzed by
tyrosinase, peroxidase, and cytochrome p450.
The metabolic pathways of dietary flavonoids are still largely
unknown. In the present work, mass spectrometry and UV-vis
spectroscopy studies were used to show that the naturally occurring
flavonoid catechin underwent enzymatic oxidation by tyrosinase in the
presence of glutathione (GSH) to form mono-, bi-, and tri-glutathione
conjugates of catechin and mono- and bi-glutathione conjugates of a
catechin dimer. A hydroxylated catechin adduct was also detected.
Using UV spectroscopy, it was shown that the catechol B-ring of
catechin was oxidized by tyrosinase to form an o-quinone which could
be reduced back to catechin with potassium borohydride or reacted with
GSH to form glutathione conjugates. The catechin-glutathione
conjugates formed had much lower distribution coefficient values than
catechin itself. When peroxidase and hydrogen peroxide were used
instead of tyrosinase, only mono-glutathione conjugates were formed
but not bi-glutathione conjugates or hydroxylated adducts. (1)H NMR
evidence showed that three different mono-glutathione conjugates on
ring B of catechin were formed by peroxidase and hydrogen peroxide.
Rat liver microsomes and NADPH or cumene hydroperoxide also catalyzed
catechin-glutathione conjugate formation which was prevented by
benzylimidazole, a P450 2E1 inhibitor. Catechin cytotoxicity toward
isolated hepatocytes was also markedly enhanced by hydrogen peroxide
or cumene hydroperoxide and was prevented by benzylimidazole,
suggesting that catechin could be metabolically activated by P450
peroxidase activity to form cytotoxic quinoid species. PMID: 11453730
From: Kofi on
In article
<5160df3e-a793-440f-b8b6-7c780a27d1d8(a)v38g2000vbb.googlegroups.com>,
jay <jaym1212(a)hotmail.com> wrote:

> > Given that supplemental carnitine in liposomes has alleviated TNBS
> colitis in mice when TNBS downregulates OCTN2, I'd say it's causative
> [PMID 17065219]. The other limiting factor might be glutamine (via
> the
> Atb0+ transporter).
....
> Per your advice, I recently added carnitine and alpha lipoic acid
> (ALA) and they both reduce the tongue burn.

You should try reading the references and the earlier posts I've made on
the subject. Carnitine might only be effective 1) if you can get it
across the cell membrane (like in liposomes or by boosting OCTN2
expression via intermittent fasting, exercise, PPARalpha agonists or
other means I've discussed) and 2) if you consume carnitine in
conjunction with butyrate - *however* if your colitis is due to a virus
then butyrate may only aggravate its replication (especially in
conjunction with a vitamin D3 deficiency).

And of the two, ALA seems
> to be more effective. It also seems my "food allergies" which manifest
> itself as itching, sharp intermittent shooting pains and hand
> numbness have been reduced, at least for black pepper and raw
> hazelnuts. And I can ingest more beans before incurring a heartburn.

Pepper is going to activate TRPV's which isn't exactly antiinflammatory
for some people.

> But I am wondering if I have the OCTN1 vs OCTN2 defect which would
> prevent the plant derived antioxidant, ergothioniene, from being
> accumulated in related tissues (ie skin, gut, endothelial lining,
> eyes, joints, immune cells, nervous system). OCTN1 variants are also
> linked to CD, RA, lupus, psoriasis and leukemia.

In digestive disorders I think it might be a *gain* of function and it
might be a problem due to antibodies against bacteria cross-reacting
with the receptor. This has been discussed here before as well.

A loss of transport via OCTN1 might occur due to antibodies blocking it
- and upregulating the receptor might only result in more antibody
problems - but this is but one interpretation.

>
> Recent I experimented with cooked vs raw bananas and strawberries. For
> some reason cooked cause less tongue burn than raw ones. Anyone else
> experience this? What might be the reason?

These fruits are too sweet. Sugar feeds inflammation. Cooking fruit is
particularly problematic as it generates all sorts of advanced glycation
end products.

I don't see why you don't simply try eliminating these foods first if
they're giving you trouble. None of them are essential to a balanced
diet.

> Have you noticed that an apple or potato turns brown when cut or
> bruised. Supposedly, the enzyme tyrosinase converts some polyphenols
> into quinones. Quinones are quite reactive and apparently have anti-
> viral, bacterial, insect and worm properties.

People actually take worm eggs to force Crohn's into remission. It
works well for me. <www.ovamed.de>

>
> In humans, a similar process is used to produce melanin. Here tyrosine
> is oxidized by tyrosinase into quinones and then further into melanin.
> Supposedly ingested dietary polyphenols are also oxidized into
> quinones. And neurotransmitters (ie adrenaline) are also oxidized into
> quinones. Coincedentally, I get bloating and nerve pain from elevated
> stress. And according to some abstracts, vitiligo (white skin) may be
> related to quinones also.

Vitiligo is not simply "white skin." It's loss of pigmentation. It can
happen due to loss of beta-endorphins, vitamin D3, catalase and - if I'm
not mistaken - even cAMP can be involved. There appears to be a link to
Parkinson's.

Might I suggest testing for anti-folate receptor antibodies and folate
levels. A folate deficiency would inhibit your ability to make proper
use of Vitamin D3. In combination with a carnitine deficiency, that
could explain the neuropathy, the cancer, the autoimmunity and the
cataracts. You might want to run a general metabolic panel if you
haven't already, particularly looking at carnitine, vitamin D3 and B
vitamins. I've discussed how to address various parts of these problems
before.