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Nature
2016 Aug 25;5367617:446-50. doi: 10.1038/nature19062.
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Molecular modifiers reveal a mechanism of pathological crystal growth inhibition.
Chung J
,
Granja I
,
Taylor MG
,
Mpourmpakis G
,
Asplin JR
,
Rimer JD
.
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Crystalline materials are crucial to the function of living organisms, in the shells of molluscs, the matrix of bone, the teeth of sea urchins, and the exoskeletons of coccoliths. However, pathological biomineralization can be an undesirable crystallization process associated with human diseases. The crystal growth of biogenic, natural and synthetic materials may be regulated by the action of modifiers, most commonly inhibitors, which range from small ions and molecules to large macromolecules. Inhibitors adsorb on crystal surfaces and impede the addition of solute, thereby reducing the rate of growth. Complex inhibitor-crystal interactions in biomineralization are often not well elucidated. Here we show that two molecular inhibitors of calcium oxalate monohydrate crystallization--citrate and hydroxycitrate--exhibit a mechanism that differs from classical theory in that inhibitor adsorption on crystal surfaces induces dissolution of the crystal under specific conditions rather than a reduced rate of crystal growth. This phenomenon occurs even in supersaturated solutions where inhibitor concentration is three orders of magnitude less than that of the solute. The results of bulk crystallization, in situ atomic force microscopy, and density functional theory studies are qualitatively consistent with a hypothesis that inhibitor-crystal interactions impart localized strain to the crystal lattice and that oxalate and calcium ions are released into solution to alleviate this strain. Calcium oxalate monohydrate is the principal component of human kidney stones and citrate is an often-used therapy, but hydroxycitrate is not. For hydroxycitrate to function as a kidney stone treatment, it must be excreted in urine. We report that hydroxycitrate ingested by non-stone-forming humans at an often-recommended dose leads to substantial urinary excretion. In vitro assays using human urine reveal that the molecular modifier hydroxycitrate is as effective an inhibitor of nucleation of calcium oxalate monohydrate nucleation as is citrate. Our findings support exploration of the clinical potential of hydroxycitrate as an alternative treatment to citrate for kidney stones.
Asplin,
Evaluation of the kidney stone patient.
2008, Pubmed
Asplin,
Evaluation of the kidney stone patient.
2008,
Pubmed
Asplin,
Reduced crystallization inhibition by urine from men with nephrolithiasis.
1999,
Pubmed
Becke,
Density-functional exchange-energy approximation with correct asymptotic behavior.
1988,
Pubmed
Coe,
The pathogenesis and treatment of kidney stones.
1992,
Pubmed
Davis,
The role of Mg2+ as an impurity in calcite growth.
2000,
Pubmed
Dey,
In situ techniques in biomimetic mineralization studies of calcium carbonate.
2010,
Pubmed
Ettinger,
Potassium-magnesium citrate is an effective prophylaxis against recurrent calcium oxalate nephrolithiasis.
1997,
Pubmed
Evans,
"Tuning in" to mollusk shell nacre- and prismatic-associated protein terminal sequences. Implications for biomineralization and the construction of high performance inorganic-organic composites.
2008,
Pubmed
Farmanesh,
Specificity of growth inhibitors and their cooperative effects in calcium oxalate monohydrate crystallization.
2014,
Pubmed
Farmanesh,
Natural promoters of calcium oxalate monohydrate crystallization.
2014,
Pubmed
Farmanesh,
Identifying alkali metal inhibitors of crystal growth: a selection criterion based on ion pair hydration energy.
2015,
Pubmed
Graether,
Beta-helix structure and ice-binding properties of a hyperactive antifreeze protein from an insect.
2000,
Pubmed
Grimme,
A consistent and accurate ab initio parametrization of density functional dispersion correction (DFT-D) for the 94 elements H-Pu.
2010,
Pubmed
Jung,
Probing crystallization of calcium oxalate monohydrate and the role of macromolecule additives with in situ atomic force microscopy.
2004,
Pubmed
Killian,
Mechanism of calcite co-orientation in the sea urchin tooth.
2009,
Pubmed
,
Echinobase
Loe,
Gas chromatography/mass spectrometry method to quantify blood hydroxycitrate concentration.
2001,
Pubmed
Lupulescu,
In situ imaging of silicalite-1 surface growth reveals the mechanism of crystallization.
2014,
Pubmed
Mpourmpakis,
What controls au nanoparticle dispersity during growth?
2010,
Pubmed
Olafson,
Mechanisms of hematin crystallization and inhibition by the antimalarial drug chloroquine.
2015,
Pubmed
Orme,
Formation of chiral morphologies through selective binding of amino acids to calcite surface steps.
2001,
Pubmed
Parks,
Clinical implications of abundant calcium phosphate in routinely analyzed kidney stones.
2004,
Pubmed
Perdew,
Density-functional approximation for the correlation energy of the inhomogeneous electron gas.
1986,
Pubmed
Phillips,
Citrate salts for preventing and treating calcium containing kidney stones in adults.
2015,
Pubmed
Qiu,
Molecular modulation of calcium oxalate crystallization by osteopontin and citrate.
2004,
Pubmed
Rimer,
Crystal growth inhibitors for the prevention of L-cystine kidney stones through molecular design.
2010,
Pubmed
Ryall,
The effect of urine, pyrophosphate, citrate, magnesium and glycosaminoglycans on the growth and aggregation of calcium oxalate crystals in vitro.
1981,
Pubmed
Scales,
Prevalence of kidney stones in the United States.
2012,
Pubmed
Tomazic,
A study of the phase transformation of calcium oxalate trihydrate-monohydrate.
1979,
Pubmed
Wang,
Calcium orthophosphates: crystallization and dissolution.
2008,
Pubmed
Weissbuch,
Molecular recognition at crystal interfaces.
1991,
Pubmed
Weissbuch,
Interplay between malaria, crystalline hemozoin formation, and antimalarial drug action and design.
2008,
Pubmed
van Loon,
Effects of acute (-)-hydroxycitrate supplementation on substrate metabolism at rest and during exercise in humans.
2000,
Pubmed