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Published by Newdeersci
How the heparanome interacts with the metallome
How the heparanome interacts with the metallome

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Published by: Newdeersci on Feb 17, 2010
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06/23/2010

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D. Grant (Turriff) draft articles
:
 Page 1.
Document 1.
 Notes on the Inorganic Biochemistry of Heparin/Heparan Sulphate
 Page 115
Document 2
 Recent Heparan Sulphate Research May Explain Why a Vegan Diet is Good For You
 Page 127 Doc. 3
The emerging paradigm of heparan sulphate related therapy(
 Doc 3a is an earlier edition of Doc.1);
 
 Page 137 Doc. 4
(This article argues for a role of heparan sulphate biochemistry in animal evolution);
 Page 142
Doc.5
 ______________________________________________________________ DOC. 1. Notes on the Inorganic Biochemistry of Heparin/Heparan Sulphate
 
An Incompletely Edited ‘Scrapbook’
by David Grant, B.Sc., M.Sc., Ph.D.
(Turriff, U.K.)*
Preliminary Draft of a Discussion Document (Drafted for Internet Posting, 2008;5/2/09
 
-
 
still needs more editing)
 
Research Continuation of Ideas Generated From University of Aberdeen Marishal College Research*
 
Contents:
(page 8)
 
Summary
2
(page9)
IntroductionHeparin (H) can apparently sequester the full range of inorganic ions whichoccur in seawater/biological fluids by a mechanism which tends to favour the uptake of the least abundant elements present
 
2.1 (
page 10
) A suggested inorganic ion nutrient gathering and other functions of extracellularpolysaccharides
 
2.2 Available information on the association of multi-inorganic-elements with naturalpolyanionic substances 
Possible quality control problems with use
 
of 
H
for academic researches and
for future therapeutic applications
2.2-1 Countercation-specific (polarization-power-related) interation of metal ionswith –C-(O)O
-
groups in
H/Heparan Sulphate (HS)
2.3 The Haraguchi Hypothesis Extended to Polysaccharides
Metallomics & polysaccharides2.4(
page 12
) The Heparanome Metallome
A putative H/HS inorganic environment interface system
 
2.4-1
(page13)
Summary of the origin of the heparanome-metallome hypothesis
2.4-1-1
(page 14)
Examples of literature reports of metal ion driven H/HS signaling
 
2.4-1-2 Comparison of ‘metallomic’multi-inorganic-element arrays in anionic polysaccharideswith those in other matrices
2.4-2 Further evidence that multivalent inorganic element metal ions binding to H and HSproteoglycans
in vivo
 
2.4-3
 
H/HS
is an evolutionary designed flexible metal ion binding system
Polysaccharides, especially the polyuronates and highly anionic glycosaminoglycans, seem to be especiallydesigned to act, in conjunction with other anionic systems, as multi-element metallomic ligands. 2.5
(page 16)
Evidence for ‘all-element’- decorated H 
2.5-1
 
SSMS-determined inorganic elements associated with an experimental Na
H
 
(more accurately Na/Ca = ca.6, H) (believed to represent the inorganic componentspresent in mast cell derived pharmaceutical H before final ‘heavy metal clean-up’) 
2.5-2 SSMS determined inorganic elements associated with an experimental Tl
H
 2.6 Summary of apparent effect on metallomic profiles of 
Heparin
leached from blood
 
collection containersICP-MS studies of 
H
 2.6.1(
page 18
) Re-evaluation of SSMS Data for Na
H
and comparison with ICP-MS data
2.7
(page 18)
 
Toxic Inorganic Elements in the Natural Anionic Polysaccharides 2.7-1 Toxic inorganic elements in
H
 2.7-2 Multi-inorganic-elements in common laboratory reagents
 
2.8 Other suggested metallomic-related activities of animal polysaccharides: modulation of water supramolecular structure, calcification and deactiviation of Fenton reactioncatalysts
2.8-1
(page 19)
Other cell surface polyanion (putative metallomic) systems:
 
 polyphosphate, poly-
β
hydroxybutyrate & teichoic acids2.8-2 Possible inorganic phosphate-containing high afffinity metal ion binding sites in
H
2.9 Metal ion assisted polysaccharide-protein binding could be relevant to the current
discussions of how different HS polymers selectively binding by variants of FGF
in vivo
2.9-1 Servo-feedback signaling
via
the heparanome-metallome could have facitlitatedanimal evolution2.9-2
(page20)
Inorganic cofactors for nitrosative structural alteration of 
H/HS
2.9-3 The selective degradation of 
Heparin
/
HS
by action of redox metal ions2.9-4 How different
HS
polymers could selectively bind variant of FGF
in vivo
: hintsfrom lipoprotein binding studies
2.10
(page 21)
Comparison of Different Multi-Inorganic-Element Matrices
 
---------------------------------------------------------------------------------------------------------------------------------
 
3
 
(page21)
Ca
2+
signaling
via
the heparanome –metallome 
The suggested primary functions of the heparanome-metallome;
 
The hypothesis that Ca
2+
and other inorganic ions modulate
HS
activites
[The Long -Williamson
1
hypothesis :
HS
controls Ca
 
2+
 
activity
 The control of activities of Ca
2+
(e.g. at pericellular environments) were suggested to be the primary function of 
HS
. This general idea can now, however, be modified to suggest that Ca
2+
and other inorganic ions might modulate
HS
activities by modulating biopoymer water activities whichaffect 
H/HS
-
 
 protein interactions]
3.1
(page 22)
In plants Ca
2+
and other inorganic ions are believed to modulate polyanonic polysaccharideactivities
3.2 Evidence from knockout mice that
HS
N - SO
3-
groups potentiate
HS
- determined Ca
2+
activities required for skeletal muscle function(Ndst-1 -/- mice are reported to show reduced Ca
2+
kinetics in myotubes)3.3
(page 22)
Heparin/HS
& control of calcification
 
3.3-1(
page23
)N-SO
3-
is involved in Ca
2+
binding by
Heparin/HS
 3.4 Proposed roles of inorganic borate, silicate, arsenic (oxides) and phosphateattached to
H/HS
3.4-1 Specific nucleation activities (
e.g 
. afforded by natural ‘SiO
2
’ nanoparticles) may berequired for supramolecular structure formation in polysaccharides3.4.-2
 
Polyoxymetalates and biologically relevent
Heparin/HS
catalytic activityPossible role of anionic polysaccharides in the assembly of polyoxymetalates-polysaccharides with primitive enzymic activity3.4-3(
page 24
)
 
Heparin/HS
& Metalloproteinases (
MMP
s): a putative further example of metal ion (andwater structure?) determined activity –related effects3.4-3-1
 
Modulation of metalloproteinase activity by arsenic suggests a possible therapeuticapplication of As
2
O
3
-
H/HS
as an anti-cancer agent
 
3.4-4(
page 24
)
Heparin/HS
& Sulfatase activites; postsynthetic editing of 
HS
sequences; role of metallomics? 
6-O-Endosulphatase (Sulf) action in ‘smart’
HS
microstructure modulation
3.4-5
Heparin/HS
& kallikrein: could exemplify how
HS
determines water structure/activity
HS
signaling (thyroid hormone dependent) in skeletal growth & mineralization –[inorganic biochemistry related systems]3.4-6 The use use of barium acetate buffer for the electrophoretic separation
via
selective binding of Ba
2+
to
Heparin/HS
 
3.5 Mineralization (inorganic biochemistry related systems)3.5-1 Thyroid hormone dependent skeletal growth
etc.
 
Plaque formation &
Heparin/HS
 
The inhibition of various forms of proteinaceous and inorganic plaques by themost highly sulphated fractions of 
Heparin/HS
and related substances (such as PPS)could be why such preparations show great promise for the therapeutic interventionin those diseases which are believed to be promoted by the formation of such plaques ** [
Cf 
. also Section 6.3].
3.5-2-1(
page26
) Phospholipid
Heparin/HS
interaction with metal ions3.5-2-2 Polysaccharide metal ion dependent aggregation3.5-2-3 (
page26
) Nucleation events (subject to potential inhibition by
Heparin/Heparan S
)may determine the progression of amyloidoses3.5-2-4 Polysaccharide inorganic ion dependent gelation and melting3.5-3
(page 27)
Binding of anionic polysaccharides to crystal surfaces3.5-3-1 Relevance of control of inorganic crystal morphology to evolution of precursors of life3.5.4(
page29
) How information in anionic polysaccharides can be ‘read-off’ by crystal structures----------------------------------------------------------------------------------------------------------------------------------4
WATER & LIFE  –ROLE OF POLYSACCHARIDES 
 

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