AC Immune SA, Lausanne, Switzerland.
Biophys Chem. 2010 Apr;147(3):93-103. doi: 10.1016/j.bpc.2010.01.005. Epub 2010 Jan 29.
Obesity is a serious public health concern with an increasing prevalence worldwide. The diet contributes strongly to this problem and high-fat food leads to unhealthy conditions. Fat digestion is an energy intensive process as it requires hydrolysis to allow the body to profit from this nutrient. This additional energy expenditure is also present in a highly redundant hormonal regulation system for fat storage which is converted in not a readily accessible form (therefore, an upstream is required in order to tackle fat-related diseases). Due to the low water solubility of oils and fats, the lipase catalyzed reactions take place at a specific locus, the oil-water interface. Despite considerable efforts in the past the effects of the interfacial composition on lipase activity have been only qualitatively understood until recently. It has recently been undertaken a detailed study of the interfacial behavior of lipases, their substrates and products which have contributed to shed light into the mechanism of lipolysis [1-4]. In addition, there are strong evidences that lipase activity is a function of interfacial composition and changes concurrently with lipolytic conversion [1]. In these cases lipase "inhibition" should be attributed to substrate depletion and not to lipase desorption or denaturation as previously hypothesized [5]. This self-limiting effect through the feedback of interfacial composition to the reaction conditions of the enzyme opens a new avenue to control lipase catalysis through the interface. A set of experiments are proposed which can be performed to further characterize and gain a deeper insight into interfacial enzymology.
肥胖是一个严重的公共卫生问题，在全球范围内呈上升趋势。饮食是导致这个问题的主要原因，高脂肪食物会导致健康状况不佳。脂肪消化是一个能源密集型的过程，因为它需要水解才能使身体从这种营养物质中获益。脂肪储存的高度冗余激素调节系统也存在这种额外的能量消耗，这种系统会将脂肪转化为不易被利用的形式（因此，需要一个上游系统来解决与脂肪相关的疾病）。由于油和脂肪的低水溶性，脂肪酶催化的反应发生在特定的位置，即油水界面。尽管过去做出了相当大的努力，但直到最近，界面组成对脂肪酶活性的影响才被定性地理解。最近对脂肪酶、其底物和产物的界面行为进行了详细的研究，这有助于揭示脂肪分解的机制[1-4]。此外，有强有力的证据表明，脂肪酶活性是界面组成的函数，并随着脂肪酶水解的转化而变化[1]。在这些情况下，脂肪酶“抑制”应该归因于底物耗尽，而不是脂肪酶解吸或变性，如以前假设的那样[5]。通过界面组成对酶反应条件的反馈的这种自我限制效应为通过界面控制脂肪酶催化开辟了新途径。提出了一系列可以进一步进行的实验，以进一步表征和深入了解界面酶学。
