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Biologically relevant physical studies of insulin-enhancing vanadium complexes Liboiron, Barry D.
Abstract
Investigations of the in vivo transport and accumulation of insulin-enhancing vanadium complexes are presented. Detailed spectroscopic studies of bis(maltolato)oxovanadium(IV) (BMOV), bis(ethylmaltolato)oxovanadium(IV) (BEOV) and the inorganic salt vanadyl sulfate (VOSO4) were carried out on in vitro solutions of serum proteins, and in vivo tissue samples from animals previously treated with a vanadium complex. Serum proteins apo-transferrin and albumin are both capable of effecting the decomposition of BMOV and BEOV under physiological conditions (pH 7.4, 0.16 M NaCl) to form vanadyl-protein adducts. Interactions of these complexes with the proteins were studied by continuous wave electron paramagnetic resonance (EPR) and difference ultraviolet spectroscopies. Apo-transferrin can bind up to two equivalents of BMOV at the Fe(III) binding sites, but (bi)carbonate (or another suitable synergistic anion) must be present for vanadyl binding to take place. The inability of maltolate to act in this role is demonstrated. Chelated vanadyl sources show no preference for either the N - or C-terminus binding site. Albumin binds BMOV only at the strong Cu(II) binding site; the presence of maltol imparts a site selectivity to the system in that BMOV will not bind at exposed carboxylates. Through consideration of the active equilbria in solution, formation of a ternary maltol-vanadyl-albumin complex is proposed and discussed in terms of reactivity differences between BMOV and VOS04 and transport of chelated vanadyl sources in the bloodstream. Pulsed EPR methods - electron spin echo envelope modulation (ESEEM) and hyperfine sublevel correlation (HYSCORE) - were used to study the in vivo coordination of vanadyl ions in rat kidney, liver and bone samples, which had been previously taken from animals chronically administered BEOV via drinking water. The chelated vanadyl source becomes ligated by amines in the kidney and liver, and by as many as three different phosphate groups in bone mineral. Model studies of the vanadyl-triphosphate and vanadylhydroxyapatite systems were also studied to gain structural insights into the in vivo coordination state of the vanadyl ions in bone. Both systems proved to be very good models of the in vivo complex. Based on the number and relative magnitudes of the isotropic and anisotropic ³¹P and ¹H coupling constants, a proposed solution structure, consistent with all spectroscopic data, is presented.
Item Metadata
Title |
Biologically relevant physical studies of insulin-enhancing vanadium complexes
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Creator | |
Publisher |
University of British Columbia
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Date Issued |
2002
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Description |
Investigations of the in vivo transport and accumulation of insulin-enhancing
vanadium complexes are presented. Detailed spectroscopic studies of
bis(maltolato)oxovanadium(IV) (BMOV), bis(ethylmaltolato)oxovanadium(IV) (BEOV) and
the inorganic salt vanadyl sulfate (VOSO4) were carried out on in vitro solutions of serum
proteins, and in vivo tissue samples from animals previously treated with a vanadium
complex. Serum proteins apo-transferrin and albumin are both capable of effecting the
decomposition of BMOV and BEOV under physiological conditions (pH 7.4, 0.16 M NaCl)
to form vanadyl-protein adducts. Interactions of these complexes with the proteins were
studied by continuous wave electron paramagnetic resonance (EPR) and difference ultraviolet
spectroscopies. Apo-transferrin can bind up to two equivalents of BMOV at the
Fe(III) binding sites, but (bi)carbonate (or another suitable synergistic anion) must be present
for vanadyl binding to take place. The inability of maltolate to act in this role is
demonstrated. Chelated vanadyl sources show no preference for either the N - or C-terminus
binding site. Albumin binds BMOV only at the strong Cu(II) binding site; the presence of
maltol imparts a site selectivity to the system in that BMOV will not bind at exposed
carboxylates. Through consideration of the active equilbria in solution, formation of a
ternary maltol-vanadyl-albumin complex is proposed and discussed in terms of reactivity
differences between BMOV and VOS04 and transport of chelated vanadyl sources in the
bloodstream. Pulsed EPR methods - electron spin echo envelope modulation (ESEEM) and
hyperfine sublevel correlation (HYSCORE) - were used to study the in vivo coordination of
vanadyl ions in rat kidney, liver and bone samples, which had been previously taken from
animals chronically administered BEOV via drinking water. The chelated vanadyl source
becomes ligated by amines in the kidney and liver, and by as many as three different
phosphate groups in bone mineral. Model studies of the vanadyl-triphosphate and vanadylhydroxyapatite
systems were also studied to gain structural insights into the in vivo
coordination state of the vanadyl ions in bone. Both systems proved to be very good models
of the in vivo complex. Based on the number and relative magnitudes of the isotropic and
anisotropic ³¹P and ¹H coupling constants, a proposed solution structure, consistent with all
spectroscopic data, is presented.
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Extent |
9068291 bytes
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Genre | |
Type | |
File Format |
application/pdf
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Language |
eng
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Date Available |
2009-09-15
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Provider |
Vancouver : University of British Columbia Library
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Rights |
For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.
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DOI |
10.14288/1.0061319
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URI | |
Degree | |
Program | |
Affiliation | |
Degree Grantor |
University of British Columbia
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Graduation Date |
2002-11
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Campus | |
Scholarly Level |
Graduate
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Aggregated Source Repository |
DSpace
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Rights
For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.