title: Biocalcite and Carbonic Acid Activators.
abstract: Based on evolution of biomineralizing systems and energetic considerations, there is now compelling evidence that enzymes play a driving role in the formation of the inorganic skeletons from the simplest animals, the sponges, up to humans. Focusing on skeletons based on calcium minerals, the principle enzymes involved are the carbonic anhydrase (formation of the calcium carbonate-based skeletons of many invertebrates like the calcareous sponges, as well as deposition of the calcium carbonate bioseeds during human bone formation) and the alkaline phosphatase (providing the phosphate for bone calcium phosphate-hydroxyapatite formation). These two enzymes, both being involved in human bone formation, open novel not yet exploited targets for pharmacological intervention of human bone diseases like osteoporosis, using compounds that act as activators of these enzymes. This chapter focuses on carbonic anhydrases of biomedical interest and the search for potential activators of these enzymes, was well as the interplay between carbonic anhydrase-mediated calcium carbonate bioseed synthesis and metabolism of energy-rich inorganic polyphosphates. Beyond that, the combination of the two metabolic products, calcium carbonate and calcium-polyphosphate, if applied in an amorphous form, turned out to provide the basis for a new generation of scaffold materials for bone tissue engineering and repair that are, for the first time, morphogenetically active.
authors.affiliation: ERC Advanced Investigator Group, Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, Duesbergweg 6, 55128, Mainz, Germany. wang013@uni-mainz.de.|NanotecMARIN GmbH, Duesbergweg 6, 55128, Mainz, Germany. wang013@uni-mainz.de.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Wang
authors.affiliation: ERC Advanced Investigator Group, Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, Duesbergweg 6, 55128, Mainz, Germany.
authors.forename: Meik
authors.initials: M
authors.lastname: Neufurth
authors.affiliation: ERC Advanced Investigator Group, Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, Duesbergweg 6, 55128, Mainz, Germany.
authors.forename: Emad
authors.initials: E
authors.lastname: Tolba
authors.affiliation: ERC Advanced Investigator Group, Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, Duesbergweg 6, 55128, Mainz, Germany.
authors.forename: Shunfeng
authors.initials: S
authors.lastname: Wang
authors.affiliation: ERC Advanced Investigator Group, Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, Duesbergweg 6, 55128, Mainz, Germany.|NanotecMARIN GmbH, Duesbergweg 6, 55128, Mainz, Germany.
authors.forename: Heinz C
authors.initials: HC
authors.lastname: Schröder
authors.affiliation: ERC Advanced Investigator Group, Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, Duesbergweg 6, 55128, Mainz, Germany. wmueller@uni-mainz.de.|NanotecMARIN GmbH, Duesbergweg 6, 55128, Mainz, Germany. wmueller@uni-mainz.de.
authors.forename: Werner E G
authors.initials: WE
authors.lastname: Müller
mesh_terms: D000469:Alkaline Phosphatase / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001688:Biological Products / Q000737:chemistry / Q000494:pharmacology; D001846:Bone Development / Q000187:drug effects*; D001842:Bone and Bones / Q000187:drug effects / Q000201:enzymology*; D002119:Calcium Carbonate / Q000378:metabolism*; D002130:Calcium Phosphates / Q000378:metabolism*; D002255:Carbonic Acid / Q000378:metabolism; D002256:Carbonic Anhydrases / Q000187:drug effects / Q000378:metabolism*; D004353:Drug Evaluation, Preclinical / Q000639:trends; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D011161:Porifera / Q000737:chemistry
chemical_list: D001688:Biological Products; D002130:Calcium Phosphates; D002255:Carbonic Acid; D000469:Alkaline Phosphatase; D002256:Carbonic Anhydrases; D002119:Calcium Carbonate