Inhibition of calcium hydroxyapatite formation by polyamines

Abstract

ABSTRACT— The lithogenic potential of bile depends not only on supersaturation of solutes but also on the presence of pro‐ and anti‐nucleating factors. For example, glycine‐conjugated dihydroxy bile salt dimers are potent inhibitors of calcium hydroxyapatite precipitation that function by “poisoning” the nascent crystal. Although most inhibitors of apatite formation are anions, theoretically polycations should also be effective, and because significant concentrations of polyamines are present in bile, we have investigated the ability of these molecules to inhibit apatite formation. In vitro, each polyamine (2–10 mmol/l) was able to inhibit apatite formation, and the inhibiting power was correlated with ionic charge. Thus putrescine (2+) was the weakest inhibitor and spermine (4+) was the strongest. Mixtures of polyamines were less effective than were the individual polyamines, except at higher concentrations. Although polyamines were effective over short periods of time (270 min), over longer times (3 days) spermine was unable to prevent apatite formation. Using infrared spectroscopy, we found no evidence for interaction between phosphate ions and spermine in solution. Taken together, these results suggest that polyamines are modest inhibitors of apatite formation that likely function by retarding the dissolution of the intermediate amorphous calcium phosphate phase.

Poly(ethylene imine)-Controlled Calcium Phosphate Mineralization

“…is in line with an earlier study on the effect of the low molecular weight PEI analogues spermine, spermidine, and putrescine on HAP nucleation and crystallization inhibition. 23 There, the inhibiting ability was correlated to the charge of the oligo(imines) and high charges led to strong inhibition. In our case, the templating effect can, to a large extent, also be correlated to the charge of the PEI molecules.…”

“…Nevertheless, our study supports a few earlier studies showing that not only polyanions, but also polycations have a strong influence on CaP mineralization. [23][24][25][26] In particular, a new publication by Michel et al 26 is interesting in this context. It shows that CaP mineralization can, in special cases, only proceed if a polycation is present in the reaction mixture.…”

“…5,[8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] There have been numerous studies on the effect of polyanions on CaP mineralization, but only a few studies on the influence of polycations. [23][24][25][26] Crowther et al have investigated the ability of the low molecular weight PEI analogues spermine, spermidine, and putrescine on HAP nucleation and crystallization inhibition. 23 There, the inhibiting ability was correlated with the charge of the oligo(imines).…”

“…[23][24][25][26] Crowther et al have investigated the ability of the low molecular weight PEI analogues spermine, spermidine, and putrescine on HAP nucleation and crystallization inhibition. 23 There, the inhibiting ability was correlated with the charge of the oligo(imines). Putrescine (containing two nitrogens that can be protonated) was the weakest inhibitor and spermine (four nitrogens) the strongest.…”

Acute Pancreatitis Induced by Activated Polyamine Catabolism Is Associated with Coagulopathy: Effects of α-Methylated Polyamine Analogs on Hemostasis

“…Chronic ethanol feeding induces polyamine acetylation in rat liver [19] and inhibits polyamine biosynthesis [20]. In addition, an increase in hepatic polyamine content has been attributed to the recovery from experimental cholestasis [21], and polyamines have been shown to inhibit calcium hydroxyapatite formation in bile [22]. …”