MICROCYTOPHOTOMETRIC ANALYSIS OF HUMAN OSTEOCLAST METABOLISM - LACK OF ACTIVITY IN CERTAIN OXIDATIVE PATHWAYS INDICATES INABILITY TO SUSTAIN BIOSYNTHESIS DURING RESORPTION
MICROCYTOPHOTOMETRIC ANALYSIS OF HUMAN OSTEOCLAST METABOLISM - LACK OF ACTIVITY IN CERTAIN OXIDATIVE PATHWAYS INDICATES INABILITY TO SUSTAIN BIOSYNTHESIS DURING RESORPTION
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DOI：
10.1177/42.5.8157931
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发表时间：
1994-05-01
影响因子：
3.2
通讯作者：
BRADBEER, JN
中科院分区：
文献类型：
--
作者：
DODDS, RA;GOWEN, M;BRADBEER, JN
有人提出，高度生物合成的细胞氧化脂肪酸产生 ATP，同时通过糖酵解和戊糖分流系统维持高水平的葡萄糖代谢，以提供生物合成中间体。我们研究了破骨细胞中 ATP 产生的代谢策略和底物。我们使用原位定量显微细胞光度技术来测定人体内戊糖分流（葡萄糖-6-磷酸脱氢酶；G6PD）、糖酵解途径（甘油醛-3-磷酸脱氢酶和乳酸脱氢酶；G3PD 和 LDH）、脂肪酸氧化（β-羟酰基脱氢酶；HOAD）和克雷布斯循环（琥珀酸脱氢酶；SDH）的最大活性。破骨细胞原位，并将这些酶活性与细胞参与吸收的程度相关联。与其他高度生物合成的细胞（例如软骨细胞和巨噬细胞多核细胞）不同，与骨吸收相关的破骨细胞缺乏 G3PD、LDH 和 G6PD 活性。然而，破骨细胞确实表现出脂肪酸氧化的能力，这种能力在骨表面的细胞中增加。破骨细胞中缺乏显着的糖酵解和戊糖分流活性提供了良好的证据，表明重吸收破骨细胞与吞噬巨噬细胞多核细胞不同，具有细胞的代谢特征，其从头合成 mRNA 的能力大大降低，但确实保持了高 ATP 产生率。讨论了糖酵解活性丧失是细胞死亡前奏的可能性。
It has been proposed that highly biosynthetic cells oxidize fatty acids to generate ATP while maintaining high levels of glucose metabolism through the glycolytic and pentose shunt systems to supply biosynthetic intermediates. We investigated the metabolic strategies and substrate for ATP production in the osteoclast. We used in situ quantitative microcytophotometric techniques to determine the maximal activity of the pentose shunt (glucose-6-phosphate dehydrogenase; G6PD), the glycolytic pathway (glyceraldehyde-3-phosphate dehydrogenase and lactate dehydrogenase; G3PD and LDH), fatty acid oxidation (beta-hydroxyacyl dehydrogenase; HOAD), and the Krebs cycle (succinate dehydrogenase; SDH) in human osteoclasts in situ, and related these enzyme activities to the degree of involvement of the cells in resorption. Unlike other highly biosynthetic cells, such as chondrocytes and macrophage polykaryons, osteoclasts associated with bone resorption were deficient in G3PD, LDH, and G6PD activity. However, osteoclasts did demonstrate a capacity for fatty acid oxidation which increased in cells apposed to the bone surface. The lack of significant glycolytic and pentose shunt activity in the osteoclast provides good evidence that resorbing osteoclasts, unlike phagocytosing macrophage polykaryons, have the metabolic characteristics of cells with greatly reduced capabilities of de novo mRNA synthesis but which do maintain high rates of ATP production. The possibility that the loss of glycolytic activity is a prelude to cell death is discussed.