Patel M S, Jomain-Baum M, Ballard F J, Hanson R W
J Lipid Res. 1971 Mar;12(2):179-91.
The metabolism of pyruvate and lactate by rat adipose tissue was studied. Pyruvate and lactate conversion to fatty acids is strongly concentration-dependent. Lactate can be used to an appreciable extent only by adipose tissue from fasted-refed rats. A number of compounds, including glucose, pyruvate, aspartate, propionate, and butyrate, stimulated lactate conversion to fatty acids. Based on studies of incorporation of lactate-2-(3)H and lactate-2-(14)C into fatty acids it was suggested that the transhydrogenation sequence of the "citrate-malate cycle"(1) was not providing all of the NADPH required for fatty acid synthesis from lactate. An alternative pathway for NADPH formation involving the conversion of isocitrate to alpha-ketoglutarate via cytosolic isocitrate dehydrogenase was proposed. Indirect support for this proposal was provided by the rapid labeling of glutamate from lactate-2-(14)C by adipose tissue incubated in vitro, as well as the demonstration that glutamate can be readily metabolized by adipose tissue via reactions localized largely in the cytosol. Furthermore, isolated adipose tissue mitochondria convert alpha-ketoglutarate to malate, or in the presence of added pyruvate, to citrate. Glutamate itself can not be metabolized by these mitochondria, a finding in keeping with the demonstration of negligible levels of NAD-glutamate dehydrogenase activity in adipose tissue mitochondria. Pyruvate stimulated alpha-ketoglutarate and malate conversion to citrate and reduced their oxidation to CO(2). It is proposed that under conditions of excess generation of NADH malate may act as a shuttle carrying reducing equivalents across the mitochondrial membrane. Malate at low concentrations increased pyruvate conversion $$Word$$ citrate and markedly decreased the formation of CO(2) by isolated adipose tissue mitochondria. Malate also stimulated citrate and isocitrate metabolism by these mitochondria, an effect that could be blocked by 2-n-butylmalonate. This potentially important role of malate in the regulation of carbon flow during lipogenesis is underlined by the observation that 2-n-butylmalonate inhibited fatty acid synthesis from pyruvate, but not from glucose and acetate, and decreased the stimulatory effect of pyruvate on acetate conversion to fatty acids.
对大鼠脂肪组织中丙酮酸和乳酸的代谢进行了研究。丙酮酸和乳酸向脂肪酸的转化强烈依赖于浓度。只有禁食再喂食大鼠的脂肪组织才能在相当程度上利用乳酸。包括葡萄糖、丙酮酸、天冬氨酸、丙酸和丁酸在内的多种化合物刺激了乳酸向脂肪酸的转化。基于对乳酸 -2-(³H) 和乳酸 -2-(¹⁴C) 掺入脂肪酸的研究，有人提出 “柠檬酸 - 苹果酸循环”(1) 的转氢序列并未提供从乳酸合成脂肪酸所需的全部NADPH。有人提出了一条涉及通过胞质异柠檬酸脱氢酶将异柠檬酸转化为α-酮戊二酸来形成NADPH的替代途径。体外培养的脂肪组织对乳酸 -2-(¹⁴C) 快速标记谷氨酸以及证明谷氨酸可通过主要定位于胞质溶胶中的反应被脂肪组织轻易代谢，为该提议提供了间接支持。此外，分离的脂肪组织线粒体可将α-酮戊二酸转化为苹果酸，或者在添加丙酮酸的情况下转化为柠檬酸。谷氨酸本身不能被这些线粒体代谢，这一发现与脂肪组织线粒体中NAD - 谷氨酸脱氢酶活性水平可忽略不计的证明一致。丙酮酸刺激了α-酮戊二酸和苹果酸向柠檬酸的转化，并减少了它们向CO₂的氧化。有人提出，在NADH产生过多的情况下，苹果酸可能作为一种穿梭体，携带还原当量穿过线粒体膜。低浓度的苹果酸增加了丙酮酸向柠檬酸的转化，并显著降低了分离的脂肪组织线粒体中CO₂的形成。苹果酸还刺激了这些线粒体中柠檬酸和异柠檬酸的代谢，这种作用可被2-正丁基丙二酸阻断。2-正丁基丙二酸抑制丙酮酸合成脂肪酸，但不抑制葡萄糖和乙酸合成脂肪酸，并降低了丙酮酸对乙酸转化为脂肪酸的刺激作用，这一观察结果突出了苹果酸在脂肪生成过程中调节碳流的潜在重要作用。
