抄録
It has been supposed that the malic enzyme participates in lipogenesis by supplying NADPH 1-4) . However, the results of our study suggest that the physiological function of this enzyme may concern the conversion of pyruvate to malate by oxidizing NADPH.
Male rats of the Sprague-Dawley strain were used. The malic enzyme of rat liver was purified by the method of Hsu and Lardy 5) . The boiled supernatant of the liver soluble fraction was prepared by the following procedure: the livers were homogenized in one volume of 0.25M sucrose solution, and the homogenate was centrifuged at 105,000×g for 1 hour. The resulting supernatant was heated in boiled water for 20 minutes and then centrifuged to remove any denatured protein. The enzyme activities in the conversion of malate to pyruvate were assayed essentially according to the method of Ochoa et al 6) . The activities in the conversion of pyruvate to malate by means of a purified enzyme preparation were determined by a modification of the method of Wise and Ball 4) .
The malic enzyme activity of the liver did not alter after intraperitoneal injection of malate, but increased after pyruvate administration. Moreover, it was found that a boiled supernatant of the liver soluble fraction had an inhibitory effect on the enzyme activity in the conversion of pyruvate to malate by means of a purified enzyme preparation. The activity of the enzyme capable of causing conversion of malate to pyruvate was not affected by addition of the boiled supernatant to the reaction mixture. When the enzymecontent in the liver decreased in fasted rats, the inhibition of the enzyme activity by the boiled supernatant increased. And when the enzyme content in the liver increased in refed rats, the inhibition decreased. This relationship between the activities and the inhibitions was also found in the livers of rats with hyperthyroidism and of tumor-bearing ones except those in the last stage which had lost their regulation mechanism. The malic enzyme activity in the conversion of pyruvate to malate was regulated by a factor in the soluble fraction of the liver. These results suggest that the physiological function of the malic enzyme may be to convert pyruvate to malate.
The inhibition of the enzyme activity by the boiled supernatant fraction was competitive with NADPH. Stearic acid and stearyl-CoA, like the boiledsupernatant, inhibited the enzyme activity in the conversion of pyruvate to malate competitively with NADPH, but did not inhibit the conversion of malate to pyruvate. It was revealed by column chromatography using Sephadex G-10 and silica gel that the inhibitory factors in the soluble fraction of the liver involvedfattyacids.
This enzyme is concerned with the synthesis of fatty acids and its activity is affected by them. Not only NADPH but also acetyl-CoA is necessary for the synthesis of fatty acids. Recently, it was reported that acetyl-CoA for the synthesis of fatty acids was produced from citrate by citrate cleavage enzyme and the citrate was transported from mitochondria to cytoplasm 7) . The physiological function of the malic enzyme might be to supply substrates for TCA cycle for transport of intramitochondrial acetyl-CoA to cytoplasm, that is, to regulate the malate concentration in cytoplasm.
