Kowaloff E M, Phang J M, Granger A S, Downing S J
Proc Natl Acad Sci U S A. 1977 Dec;74(12):5368-71. doi: 10.1073/pnas.74.12.5368.
We found that proline oxidase, the first enzyme of the proline degradative pathway, is inhibited by lactate. The Km of the enzyme for proline increases with increasing concentrations of lactate. Since proline can be a source for gluconeogenesis, regulation of proline degradation by lactate may serve as a mechanism for allocation of metabolic fuel sources. The marked inhibition of proline oxidase at levels of lactate that commonly occur in both genetic and acquired lactic acidosis may cause the previously unexplained hyperprolinemia seen in these metabolic disorders.
我们发现,脯氨酸降解途径的首个酶——脯氨酸氧化酶,会受到乳酸的抑制。该酶对脯氨酸的米氏常数(Km)会随着乳酸浓度的增加而升高。由于脯氨酸可以作为糖异生的一个来源,乳酸对脯氨酸降解的调节可能是一种分配代谢燃料来源的机制。在遗传性和获得性乳酸酸中毒中常见的乳酸水平下,脯氨酸氧化酶受到显著抑制,这可能导致在这些代谢紊乱中出现之前无法解释的高脯氨酸血症。