F
Frank Roy
Guest
Alf Christophersen wrote:
> On Mon, 2 Feb 2004 02:19:52 GMT, "John de Hoog" <[email protected]> wrote:
>
> >I'm surprised not to see B12 (as methylcobalamin, 500-1500 micrograms per day) and betaine. B12
> >works well with folic acid to reduce homocysteine, and betaine has been shown to reduce
> >homocysteine dramatically.
>
> One problem with betaine is that it is quite osmotic active and activated aldose reductase which
> produce sorbitol from glucose in cells, which is also osmotic active and are very little mobile
> over membranes since it is sterically hindered to pass the Cl-regulated channel that do release
> taurine and beta-alanine when cell is volume or osmotically challenged (hypoosmosis), the
> increased sorbitol steady-state concentration if rate of turnover is not increased in parallell
> with synthesis will increase osmotic pressure inside and thus force taurine and betaine to leave
> cell thus making lack of protection against hyperhomocysteinamia and lack of protection against
> uncontrolled glycation, eg. by lysine of fructose to form an Amadori product 1-amino-1-
> deoxyfructose lysine adduct) which most possibly taurine may prevent to be formed by substituting
> lysine in the normal reaction since normally, taurine will be in great excess as free amino acid
> in cells (maybe one of the reasons intake of free amino acids may be hazardous, while intake of
> taurine is not dangerous at all since that will increase protection against formation of such
> derangeous products as AGEs.
>
> (There are several articles about taurine as glycation scavenger), but here you should read
> Nature, vol 414, p. 413ff, Michael Brownlee, Biochemistry and molecular cell biology of diabetic
> complications which doesn't mention one word about taurine, but taurine is kicked out of cell by
> mechanism 1 (several articles on cell volume regulation taurine as search word, while it protects
> against glycation products, it is involved in some phosporylations, and seem to protect against
> PKC activation.
I don't want to bull jive anyone into thinking I understand this subject, but here are some further
references.
The following article involves betaine transporters and osmolytes. Betaine transporter cDNA cloning
and effect of osmolytes on its mRNA induction -
http://ajpcell.physiology.org/cgi/content/abstract/270/2/C650
Several of the references to this article also pertain to betaine and taurine transporters. The
following article also discusses metabolism and transport of organic osmolytes such as sorbitol,
betaine, and inositol as well as osmotic equilibriation.
"In some other epithelia, one of the physiological roles of taurine, a ß-aminosulfonic acid,
includes being a compatible osmolyte. For example, in the Madin-Darby canine kidney (MDCK) cell
line, their taurine content increases twofold after a rise in medium osmolality from 300 to 600
mosmol/kg. However, it was not indicated whether the measured doubling of taurine intracellular
content was adequate for taurine to provide an essential role as an osmolyte in restoring osmotic
equilibration between the internal and external milieu. Such increases are known to be in part
accountable for by stimulation of a cell inward directed sodium- and chloride-dependent taurine
transporter. This transporter has been identified in a host of epithelia and mediates Na:Cl:taurine
transport with a stoichiometric ratio of 2:1:1. In MDCK cells and a rabbit renal papillary
epithelial cell line, adaptation to imposed hypertonic stress includes transcription of genes that
encode proteins (specific enzymes and transporters) directly involved in the metabolism and
transport of organic osmolytes such as sorbitol, betaine, and inositol."
"Three groups of osmolytes are used in mammalian cells: polyalcohols, such as sorbitol and inositol;
methylamines, such as glycerophosphorylcholine and betaine; and amino acids and amino acid
derivatives, such as glycine, glutamine, glutamate, aspartate, and taurine (141, 368, 370, 371, 629,
630, 714, 719, 724, 1077, 1381). Tissue-specific utilization of the various osmolytes has been
reviewed elsewhere in detail (682)." Source: Functional Significance of Cell Volume Regulatory
Mechanisms - http://physrev.physiology.org/cgi/content/full/78/1/247
"Mammalian cells utilize a wide variety of cell volume regulatory mechanisms. For rapid adjustment
of cell volume cells release or accumulate ions through respective channels and transport systems
across the cell membrane. The most widely used mechanisms of cell volume regulatory ion release
include ion channels and KCl symport. Ion uptake is most frequently mediated by Na+ channels, Na+,
K+, 2Cl- cotransport, and Na+/H+ exchange. Chronic adjustment of cell osmolarity is accomplished by
the formation or accumulation of organic osmolytes, molecules specifically designed to create
intracellular osmolarity without interfering with cellular function. The most widely occurring
osmolytes are sorbitol, inositol, glycerophosphorylcholine, betaine, taurine, and amino acids. The
osmolytes are either synthesized by or transported into shrunken cells. During cell swelling
osmolytes can be rapidly degraded or released. Any given cell may utilize several volume-regulatory
mechanisms. Moreover, different mechanisms are utilized in different tissues. The diversity of cell
volume regulatory mechanisms allows the cells to defend the constancy of cell volume against a
myriad of challenges with relatively little impairment of cellular function." Source: The diversity
of volume regulatory mechanisms. - http://tinyurl.com/3cqdm
There are other articles co-authored by F. LANG and others on topics of a similar vane cited in
Functional Significance of Cell Volume Regulatory Mechanisms -
http://physrev.physiology.org/cgi/content/full/78/1/247#B682.
For me it is an issue of whether to supplement with betaine and if so at what level ?. What is the
net impact on AGEs, i.e., if you are supplementing with benfotiamine?
Frank
> On Mon, 2 Feb 2004 02:19:52 GMT, "John de Hoog" <[email protected]> wrote:
>
> >I'm surprised not to see B12 (as methylcobalamin, 500-1500 micrograms per day) and betaine. B12
> >works well with folic acid to reduce homocysteine, and betaine has been shown to reduce
> >homocysteine dramatically.
>
> One problem with betaine is that it is quite osmotic active and activated aldose reductase which
> produce sorbitol from glucose in cells, which is also osmotic active and are very little mobile
> over membranes since it is sterically hindered to pass the Cl-regulated channel that do release
> taurine and beta-alanine when cell is volume or osmotically challenged (hypoosmosis), the
> increased sorbitol steady-state concentration if rate of turnover is not increased in parallell
> with synthesis will increase osmotic pressure inside and thus force taurine and betaine to leave
> cell thus making lack of protection against hyperhomocysteinamia and lack of protection against
> uncontrolled glycation, eg. by lysine of fructose to form an Amadori product 1-amino-1-
> deoxyfructose lysine adduct) which most possibly taurine may prevent to be formed by substituting
> lysine in the normal reaction since normally, taurine will be in great excess as free amino acid
> in cells (maybe one of the reasons intake of free amino acids may be hazardous, while intake of
> taurine is not dangerous at all since that will increase protection against formation of such
> derangeous products as AGEs.
>
> (There are several articles about taurine as glycation scavenger), but here you should read
> Nature, vol 414, p. 413ff, Michael Brownlee, Biochemistry and molecular cell biology of diabetic
> complications which doesn't mention one word about taurine, but taurine is kicked out of cell by
> mechanism 1 (several articles on cell volume regulation taurine as search word, while it protects
> against glycation products, it is involved in some phosporylations, and seem to protect against
> PKC activation.
I don't want to bull jive anyone into thinking I understand this subject, but here are some further
references.
The following article involves betaine transporters and osmolytes. Betaine transporter cDNA cloning
and effect of osmolytes on its mRNA induction -
http://ajpcell.physiology.org/cgi/content/abstract/270/2/C650
Several of the references to this article also pertain to betaine and taurine transporters. The
following article also discusses metabolism and transport of organic osmolytes such as sorbitol,
betaine, and inositol as well as osmotic equilibriation.
"In some other epithelia, one of the physiological roles of taurine, a ß-aminosulfonic acid,
includes being a compatible osmolyte. For example, in the Madin-Darby canine kidney (MDCK) cell
line, their taurine content increases twofold after a rise in medium osmolality from 300 to 600
mosmol/kg. However, it was not indicated whether the measured doubling of taurine intracellular
content was adequate for taurine to provide an essential role as an osmolyte in restoring osmotic
equilibration between the internal and external milieu. Such increases are known to be in part
accountable for by stimulation of a cell inward directed sodium- and chloride-dependent taurine
transporter. This transporter has been identified in a host of epithelia and mediates Na:Cl:taurine
transport with a stoichiometric ratio of 2:1:1. In MDCK cells and a rabbit renal papillary
epithelial cell line, adaptation to imposed hypertonic stress includes transcription of genes that
encode proteins (specific enzymes and transporters) directly involved in the metabolism and
transport of organic osmolytes such as sorbitol, betaine, and inositol."
"Three groups of osmolytes are used in mammalian cells: polyalcohols, such as sorbitol and inositol;
methylamines, such as glycerophosphorylcholine and betaine; and amino acids and amino acid
derivatives, such as glycine, glutamine, glutamate, aspartate, and taurine (141, 368, 370, 371, 629,
630, 714, 719, 724, 1077, 1381). Tissue-specific utilization of the various osmolytes has been
reviewed elsewhere in detail (682)." Source: Functional Significance of Cell Volume Regulatory
Mechanisms - http://physrev.physiology.org/cgi/content/full/78/1/247
"Mammalian cells utilize a wide variety of cell volume regulatory mechanisms. For rapid adjustment
of cell volume cells release or accumulate ions through respective channels and transport systems
across the cell membrane. The most widely used mechanisms of cell volume regulatory ion release
include ion channels and KCl symport. Ion uptake is most frequently mediated by Na+ channels, Na+,
K+, 2Cl- cotransport, and Na+/H+ exchange. Chronic adjustment of cell osmolarity is accomplished by
the formation or accumulation of organic osmolytes, molecules specifically designed to create
intracellular osmolarity without interfering with cellular function. The most widely occurring
osmolytes are sorbitol, inositol, glycerophosphorylcholine, betaine, taurine, and amino acids. The
osmolytes are either synthesized by or transported into shrunken cells. During cell swelling
osmolytes can be rapidly degraded or released. Any given cell may utilize several volume-regulatory
mechanisms. Moreover, different mechanisms are utilized in different tissues. The diversity of cell
volume regulatory mechanisms allows the cells to defend the constancy of cell volume against a
myriad of challenges with relatively little impairment of cellular function." Source: The diversity
of volume regulatory mechanisms. - http://tinyurl.com/3cqdm
There are other articles co-authored by F. LANG and others on topics of a similar vane cited in
Functional Significance of Cell Volume Regulatory Mechanisms -
http://physrev.physiology.org/cgi/content/full/78/1/247#B682.
For me it is an issue of whether to supplement with betaine and if so at what level ?. What is the
net impact on AGEs, i.e., if you are supplementing with benfotiamine?
Frank