The presence of protein-bound gamma-carboxyglutamic acid in calcium-containing renal calculi.

Lian, Jane B.; Prien, Edwin L.; Glimcher, M J; Gallop, Paul M.

doi:10.1172/jci108739

Cited by 152 publications

(46 citation statements)

References 15 publications

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“…Our finding of no Gla in patient inhibitors contrasts with the study of Lian et al (33), who isolated from renal calculi a protein that contains Gla and resembles the ones we describe here. Calcium, but not uric acid stones, contain proteins rich in aspartic and glutamic acids, low in lysine and arginine, and possessing Gla.…”

Section: Discussioncontrasting

confidence: 99%

Urine glycoprotein crystal growth inhibitors. Evidence for a molecular abnormality in calcium oxalate nephrolithiasis.

Nakagawa¹,

Abram²,

Parks³

et al. 1985

J. Clin. Invest.

111

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One reason that some people are prone to calcium oxalate nephrolithiasis is that they produce urine that is subnormal in its ability to inhibit the growth of calcium oxalate crystals. We have identified in human urine a glycoprotein (GCI) that inhibits calcium oxalate crystal growth strongly, and at low concentrations (10-' M); in this study, we have isolated GCI molecules from the urine of normal people and patients with calcium oxalate stones. GCI from stone formers is abnormal in three ways: (1) it contains no detectable y-carboxyglutamic acid (Gla), whereas normal GCI contains 2-3 residues of Gla per mole; (2) about half of the GCI in urine of patients inhibits crystal growth 4-20 times less than normal GCI as judged by its performance in a kinetic growth assay, in vitro; (3) at the air-water interface, patient GCI has a film collapse pressure approximately half of normal. GCI molcules from the urine of patients with calcium oxalate nephrolithiasis are intrinsically abnormal, and these abnormalities could play a role in the genesis of stones.

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Section: Discussioncontrasting

confidence: 99%

Urine glycoprotein crystal growth inhibitors. Evidence for a molecular abnormality in calcium oxalate nephrolithiasis.

Nakagawa¹,

Abram²,

Parks³

et al. 1985

J. Clin. Invest.

111

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show abstract

“…1). Furthermore, Gla-containing proteins have also been noted to be present in other pathologic calcifications (11,12) and unique Glacontaining proteins have, in fact, been isolated from calcium containing renal stones (12), and calcified atherosclerotic plaque (13). In calcified plaque our group has found that Gla levels paralleled calcium content and pathologic severity (13), as is the case in the present work concerning calcified cardiac valves.…”

Section: Resultssupporting

confidence: 77%

“…Recently, Gla has been demonstrated to occur in other unique proteins of bone (8), kidney (9), and lung (10), and in proteins isolated from various pathologic calcifications including calcium containing renal stones (11,12) and calcified atherosclerotic plaque (11,13). Gla biosynthesis in liver (7), bone (14), kidney (9), and lung (10) has been demonstrated to occur as a vitamin K-dependent posttranslational, enzymatic carboxylation of specific glutamic acid residues (Fig.…”

Section: Introductionmentioning

confidence: 99%

Vitamin K-dependent Calcium Binding Proteins in Aortic Valve Calcification

Levy¹,

Zenker²,

Lian³

1980

J. Clin. Invest.

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“…With the higher CaOx supersaturation following a more extensive evaporation, this difference essentially disappeared. The exact mechanism behind this inhibition has not been elucidated, but it is reasonable to assume that liberated Ca 2+ -ions bind to γ-carboxyglutamic acid groups in the macromolecules (Lian et al, 1977;Nishio et al, 1990). Such a binding would, thus, counteract the development of a local critical supersaturation when the solution supersaturation remains low, but not when it becomes high as a result of a pronounced volume reduction.…”

Section: Discussionmentioning

confidence: 99%

Crystallization during volume reduction of solutions with a composition corresponding to that in the collecting duct: the influence of hydroxyapatite seed crystals and urinary macromolecules

Højgaard

Fornander

Nilsson

et al. 1999

Urological Research

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To examine the effect of hydroxyapatite (HAP) seed crystals and urinary macromolecules on the crystallization under conditions similar to those in the collecting duct (CD), we evaporated 100 ml samples of salt solutions with an ioncomposition assumed to correspond to that in the CD without and with HAP seed crystals. The crystallization in seeded solutions was assessed both with and without dialyzed urine (dU). After evaporation, the number and volume of crystals were recorded and the crystal morphology was examined with scanning electron microscopy (SEM) and X-ray crystallography.Addition of HAP crystals was apparently followed by an approximately 15-20% increase in heterogeneous nucleation of calcium oxalate (CaOx). In these experiments, SEM and X-ray crystallography showed a high percentage of CaOx in the precipitate.In samples reduced to 40-69 ml, addition of dU to the CD solution containing HAP seed resulted in a greater mean (SD) number of crystals: 3895(1841) in samples with dU and 1785(583) in samples without. This was mainly explained by an increased mean (SD) number of small crystals. The mean crystal volume was 17.8(1.1) and 34.3(9.1) in samples reduced to 40-69 ml with and without dU, respectively. This might reflect the inhibitory effect of dU on the growth and/ or aggregation of the CaOx-CaP precipitate or a promoted nucleation resulting in a great number of small crystals.It is concluded that calcium phosphate (CaP) formed above the collecting duct might induce heterogeneous nucleation of CaOx at lower levels of the renal collecting system, and that urinary macromolecules are powerful modifiers of these processes.

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The presence of protein-bound gamma-carboxyglutamic acid in calcium-containing renal calculi.

Cited by 152 publications

References 15 publications

Urine glycoprotein crystal growth inhibitors. Evidence for a molecular abnormality in calcium oxalate nephrolithiasis.

Urine glycoprotein crystal growth inhibitors. Evidence for a molecular abnormality in calcium oxalate nephrolithiasis.

Vitamin K-dependent Calcium Binding Proteins in Aortic Valve Calcification

Crystallization during volume reduction of solutions with a composition corresponding to that in the collecting duct: the influence of hydroxyapatite seed crystals and urinary macromolecules

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