Continuous pyruvate carbon flux to newly synthesized cholesterol and the suppressed evolution of pyruvate-generated CO2 in tumors: further evidence for a persistent truncated Krebs cycle in hepatomas.
Continuous pyruvate carbon flux to newly synthesized cholesterol and the suppressed evolution of pyruvate-generated CO2 in tumors: further evidence for a persistent truncated Krebs cycle in hepatomas.
复制标题
新合成胆固醇的持续丙酮酸碳通量和肿瘤中丙酮酸产生的二氧化碳的抑制演化：肝癌中持续截短的克雷布斯循环的进一步证据。
DOI：
10.1016/0167-4889(86)90134-5
复制
发表时间：
1986
期刊：
影响因子：
--
通讯作者：
Coleman,PS
中科院分区：
文献类型：
--
作者：
Parlo,RA;Coleman,PS
Viable tissue slices from rat liver and Morris hepatoma 3924A were compared as to their ability to incorporate carbons from [U-14C]pyruvate into newly synthesized cholesterol versus CO2. By 4 h, the tumor slice incubation had incorporated over 6-fold more pyruvate carbons into the sterol than into CO2, relative to the normal liver slice incubation, per g tissue protein. However, the presence of the mitochondrial citrate exchange carrier inhibitor 1,2,3-benzenetricarboxylate in the incubation inhibited the formation of [14C]cholesterol, while simultaneously leading to an increase in the rate of14CO2production in the tumor. In the normal liver system by contrast, benzenetricarboxylate also inhibited [14C]cholesterol formation, but had hardly any effect on the already high rate of14CO2production. The ability of benzenetricarboxylate to inhibit the rapid carbon flux from pyruvate to cholesterol, and to steer the metabolic flow of carbons toward oxidative decarboxylation via the Krebs cycle in whole, viable tumor tissue, indirectly emphasizes the importance of the mitochondrial citrate exchange carrier in supporting the decontrol of cholesterogenesis de novo in tumors by accelerating the supply of lipogenic precursor carbons to the tumor cytosol. These studies may be therefore interpreted as extensions, to the level of whole-cell metabolism, of the concept of a persistent ‘truncated’ Krebs cycle in the mitochondria of metastatic cancer tissue. This concept states, in part, that a rapid efflux of mitochondrially generated citrate would operate preferentially in tumors, and thus provide carbons continuously to the cytoplasmic compartment where the well-established deregulated pathway of cholesterogenesis occurs (Parlo, R.A. and Coleman, P.S. (1984) J. Biol. Chem. 259, 9997–10003; Coleman, P.S. and Lavietes, B.B. (1981) CRC Crit. Rev. Biochem. 11, 341–393).
