Aerobic metabolism of glucose by bone.

Osseous tissue is capable of producing net amounts of lactic acid. This has been demonstrated in viva by the measurement of arteriovenous differences (2), in vitro during incubation of slices (3), and in tissue culture (4). Because direct evidence has been lacking, it has been assumed that the Embden-Meyerhof pathway is the route of lactate formation (3). Indeed, various sections of the epiphyseal plate have been shown to contain phosphoglucoisomerase and lactic dehydrogenase (5)) and calcifying cartilage contains many of the glycolytic enzymes (6). On the other hand, the finding of glucose g-phosphate dehydrogenase activity in the epiphyseal plate (5) might indicate that the pentose cycle is also operative. The demonstration of certain enzymatic activities of the citric acid cycle, including citrogenase, aconitase and isocitric dehydrogenase (7), malic dehydrogenase (5), and succinic dehydrogenase (8), suggests that the Krebs cycle is available for further metabolism. As part of a larger study on osseous tissue, we have been interested in factors involved in bone demineralization. Since parathyroid hormone is closely involved in this problem, the recent findings (2,9) that it may alter citrate and lactate formation, or both, by bone cells have been of interest. In order to approach the problem of how parathyroid hormone might produce such changes, it seemed essential to establish first the actual participation of known pathways in the metabolism of bone. The present study was developed to assess the relative importance of the Embden-Meyerhof, pentose, and Krebs’ cycle routes to the over-all metabolism of osseous tissue. The results described below demonstrate that in epiphysealmetaphyseal bone slices incubated aerobically, lactic acid is the major metabolic end product of glucose metabolism; that the lactate thus formed seems to arise entirely from glucose; that Krebs’ cycle activity is low; and that the largest part of the lactate is formed via the Embden-Meyerhof pathway with a small contribution of the pentose cycle.