Wang Xiaohong, Neufurth Meik, Tolba Emad, Wang Shunfeng, Schröder Heinz C, Müller Werner E G
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.
Prog Mol Subcell Biol. 2017;55:221-257. doi: 10.1007/978-3-319-51284-6_7.
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.
基于生物矿化系统的进化和能量方面的考虑,现在有确凿的证据表明,从最简单的动物海绵到人类,酶在无机骨骼的形成过程中起着驱动作用。以钙矿物质为基础的骨骼为例,涉及的主要酶是碳酸酐酶(许多无脊椎动物如钙质海绵的碳酸钙基骨骼的形成,以及人类骨骼形成过程中碳酸钙生物种子的沉积)和碱性磷酸酶(为骨磷酸钙-羟基磷灰石的形成提供磷酸盐)。这两种酶都参与人类骨骼形成,为治疗骨质疏松等人类骨骼疾病的药物干预开辟了尚未开发的新靶点,可使用充当这些酶激活剂的化合物。本章重点关注具有生物医学意义的碳酸酐酶以及寻找这些酶的潜在激活剂,以及碳酸酐酶介导的碳酸钙生物种子合成与富含能量的无机多磷酸盐代谢之间的相互作用。除此之外,碳酸钙和钙多磷酸盐这两种代谢产物如果以无定形形式应用,结果证明为新一代骨组织工程和修复的支架材料提供了基础,这些材料首次具有形态发生活性。