Bracey D, Holyoak C D, Coote P J
Microbiology Department, Unilever Research Colworth, Bedford, UK.
J Appl Microbiol. 1998 Dec;85(6):1056-66. doi: 10.1111/j.1365-2672.1998.tb05271.x.
The effects of sorbic acid and amphotericin B on the growth and intracellular pH (pHi) of Saccharomyces cerevisiae were studied and compared. Past evidence has suggested that the inhibitory action of sorbic acid on yeast is due to reduction of pHi per se. However, using a novel method to measure pHi in growing cells, little correlation was found between reduced growth rate on exposure to sorbic acid and reduction of pHi. In fact, growth inhibition correlated with an increase in the intracellular ADP/ATP ratio due to increased ATP consumption by the cells. This was partly attributed to the activation of protective mechanisms, such as increased proton pumping by the membrane H(+)-ATPase, which ensured that pHi did not decline when cells were exposed to sorbic acid. Therefore, the available evidence suggested that the inhibitory action of sorbic acid was due to the induction of an energetically expensive protective mechanism that compensated for any disruption of pHi homeostasis but resulted in less available energy for normal growth. In contrast to sorbic acid, with amphotericin B there was a direct correlation between growth inhibition and reduction of pHi due to the uncoupling effect of this compound on the plasma membrane. The inhibitory effect of amphotericin B was consistent with membrane disruption, or 'proton-uncoupling' leading to growth inhibition due to proton influx, decline in pHi and partial dissipation of the proton gradient.
研究并比较了山梨酸和两性霉素B对酿酒酵母生长及细胞内pH值（pHi）的影响。过去的证据表明，山梨酸对酵母的抑制作用是由于pHi本身降低所致。然而，使用一种新方法来测量生长中细胞的pHi时，发现接触山梨酸后生长速率降低与pHi降低之间几乎没有相关性。事实上，生长抑制与细胞内ADP/ATP比值增加相关，这是由于细胞ATP消耗增加所致。这部分归因于保护机制的激活，如膜H(+)-ATP酶质子泵增加，这确保了细胞接触山梨酸时pHi不会下降。因此，现有证据表明，山梨酸的抑制作用是由于诱导了一种能量消耗高昂的保护机制，该机制补偿了pHi稳态的任何破坏，但导致正常生长可用能量减少。与山梨酸不同，两性霉素B导致生长抑制与pHi降低直接相关，这是由于该化合物对质膜的解偶联作用。两性霉素B的抑制作用与膜破坏或“质子解偶联”一致，导致质子内流、pHi下降和质子梯度部分耗散从而抑制生长。
