Interfacial mechanism of lipolysis as self-regulated process.
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.
Reis
P
P
AC Immune SA, Lausanne, Switzerland. pedro.reis@acimmune.com
Watzke
H
H
Leser
M
M
Holmberg
K
K
Miller
R
R
D055162:Biocatalysis; D005223:Fats / Q000378:metabolism*; D006801:Humans; D008049:Lipase / Q000378:metabolism*; D008066:Lipolysis
D005223:Fats; D008049:Lipase