CHELATION

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CHELATION
Chelate ring structure formed by interaction of
Cation
bi- or trivalent
Electron-donating group
biomacromolecule
organic medicinal compound
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CHELATION

bivalent copper
glycine anion
11 glycine copper complex
chelating agent (ligand)
chelate
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CHELATION
Chelate ring structure formed by interaction of
Cation
bi- or trivalent
Electron-donating group
biomacromolecule
organic medicinal compound
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INTERACTION OF CATION WITH BIOMACROMOLECULE
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INTERACTION OF CATION WITH BIOMACROMOLECULE
Vitamin B12
4 pyrrole
cyano
benzimidazole
ribofuranose
cobalt
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INTERACTION OF CATION WITH BIOMACROMOLECULE
Hemoglobin
4 pyrrole
globin
iron
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INTERACTION OF CATION WITH BIOMACROMOLECULE
Chlorophyll
4 pyrrole
phytyl
magnesium
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INTERACTION OF CATION WITH BIOMACROMOLECULE
Cation-dependent Enzymes
Carboxypeptidase (ACE) Zn
Xanthine oxidase Mo
Carbonic anhydrase Zn
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CHELATION
Chelate ring structure formed by interaction of
Cation
bi- or trivalent
Electron-donating group
biomacromolecule
organic medicinal compound
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INTERACTION OF CATION WITH ORGANIC MEDICINAL
COMPOUND
Carboxypeptidase (ACE)
liver
kidney
angiotensinogen
bradykinin
renin
angiotensin I
ACE
angiotensin II
aldosterone
inactive fragments
increased bp
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INTERACTION OF CATION WITH ORGANIC MEDICINAL
COMPOUND
ACE inhibitors
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INTERACTION OF CATION WITH ORGANIC MEDICINAL
COMPOUND
ACE inhibitors
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INTERACTION OF CATION WITH ORGANIC MEDICINAL
COMPOUND
ACE inhibitors
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INTERACTION OF CATION WITH ORGANIC MEDICINAL
COMPOUND
Allopurinol
xo
xo
hypoxanthine
xanthine
uric acid
xo
allopurinol
alloxanthine
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INTERACTION OF CATION WITH ORGANIC MEDICINAL
COMPOUND
Carbonic anhydrase
CA
RBC CO2 transport from tissue to lung
Kidney H3O proton exchanged for Na
Na is reabsorbed
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INTERACTION OF CATION WITH ORGANIC MEDICINAL
COMPOUND
Acetazolamide
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INTERACTION OF CATION WITH ORGANIC MEDICINAL
COMPOUND
Penicillamine
MOA Chelation of Cu2
Wilsons disease
Rheumatoid arthritis
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INTERACTION OF CATION WITH ORGANIC MEDICINAL
COMPOUND
Deferoxamine
MOA Chelation of Fe3
Chelation of Al3
Fe poisoning
Al poisoning
End stage renal disease
Malaria?
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INTERACTION OF CATION WITH ORGANIC MEDICINAL
COMPOUND
Hydroxyquinolines
MOA Chelation of Cu2, Fe3
Salicylic acid
MOA Chelation of Cu2
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INTERACTION OF CATION WITH ORGANIC MEDICINAL
COMPOUND
EDTA
MOA Chelation of Hg2, Pb2
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INTERACTION OF CATION WITH ORGANIC MEDICINAL
COMPOUND
EDTA Chelation Therapy for Atherosclerosis
Conspiracy? Chelation works. It does not
require double blind experiments to
visibly observe the obvious.
The fundamental reason that
chelation therapy is not accepted and
promoted is to protect the coronary bypass
surgery market.
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INTERACTION OF CATION WITH ORGANIC MEDICINAL
COMPOUND
EDTA and Atherosclerosis
The Case For
The Case Against
Chelates Ca2 in plaques resulting in
dissolution.
Ca not involved in initiation of atherosclerosis.
Ca is deposited after plaque well formed minor
component.
Ca in plaques is elemental and not ionic.
Ca removed from blood is replaced from bone.
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INTERACTION OF CATION WITH ORGANIC MEDICINAL
COMPOUND
EDTA and Atherosclerosis
The Case For
The Case Against
Removes heavy metals which impair activity of
antioxidant enzymes (free radical scavengers).
No evidence to support presence of high levels of
heavy metals.
EDTA infusion also includes high-dose vitamins
(including antioxidant vitamins), minerals.
Free radicals are formed continuously, thus
ongoing (i.e not just once/yr) therapy required
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INTERACTION OF CATION WITH ORGANIC MEDICINAL
COMPOUND
EDTA and Atherosclerosis
The Case For
The Case Against
Numerous testimonials supporting effectiveness.
EDTA infusion also includes high- dose vitamins,
minerals.
EDTA therapy also includes lifestyle changes.
Claims are anecdotal and not supported by
scientific studies.
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INTERACTION OF CATION WITH ORGANIC MEDICINAL
COMPOUND
EDTA and Atherosclerosis
The Case For
The Case Against
Has been around for decades, therefore safe.
Hypocalcemia nephrotoxicity - deaths reported
GIT distress
Caution or contraindication with CHF,
arrhythmias, diabetes, impaired renal function,
epilepsy, hypertension, hypocalcemia.
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INTERACTION OF CATION WITH ORGANIC MEDICINAL
COMPOUND
EDTA Chelation Therapy for Atherosclerosis
The treatment i.v. infusion over 3 to 5 hrs
2 to 4 times per week (yearly)
30 to 50 sessions
infusion includes up to 3 gm. EDTA, various
vitamins, minerals may also include lidocaine,
heparin
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INTERACTION OF CATION WITH ORGANIC MEDICINAL
COMPOUND
EDTA Chelation Therapy for Atherosclerosis
The cost balloon angioplasty 15,000
bypass surgery 50,000
Vicky Maclean Edmonton Sun April 14, 1996
chelation therapy 3 - 5,000
cost of 3 gm. EDTA from chemical catalog
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INTERACTION OF CATION WITH ORGANIC MEDICINAL
COMPOUND
EDTA Chelation Therapy for Atherosclerosis
Does it work?
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INTERACTION OF CATION WITH ORGANIC MEDICINAL
COMPOUND
Tetracyclines
Chelate Ca2, Mg2, Fe3, Al3
chelates cations in teeth, bone
chelates cations in foods, other products
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INTERACTION OF CATION WITH ORGANIC MEDICINAL
COMPOUND
Quinolones
Chelate Ca2, Mg2, Fe3, Al3
chelates cations in foods, other products
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INTERACTION OF CATION WITH ORGANIC MEDICINAL
COMPOUND
Deferiprone
MOA Chelation of Fe3, Al3
treatment of thalassemia
aluminum poisoning
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CATION is a COMPONENT OF ORGANIC MEDICINAL
COMPOUND
Auranofin
rheumatoid arthritis
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CATION is a COMPONENT OF ORGANIC MEDICINAL
COMPOUND
Cisplatin
Platins
Nedaplatin
Carboplatin
anticancer
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CATION is a COMPONENT OF ORGANIC MEDICINAL
COMPOUND
Vanadium
metavanadate
orthovanadate
vanadyl sulfate
antidiabetic
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SIDEROPHORES
chelating agents synthesized and excreted by
microbes
facilitate active transport of chelated iron into
microbial cell
most use hydroxamic acid or catechol groups as
the chelating components of the siderophore
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SIDEROPHORES
hydroxamic acid-type
catechol-type
Mixed ligands?
Reduced resistance!
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SIDEROPHORES
How can this information be used?
Siderophore (Fe)
drug
linker/spacer
Iron transport-mediated drug delivery!
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SIDEROPHORES
siderophore
drug