Mechanisms of Inhibition of Triacylglycerol Hydrolysis by
Human Gastric Lipase*
Yan
Pafumi,
Denis
Lairon,
Paulette Lechene
de la Porte,
Christine
Juhel,
Judith
Storch
,
Margit
Hamosh§, and
Martine
Armand¶
From Unité 476-INSERM (National Institute of Health and
Medical Research)/Université de la Méditerranée, 18 avenue Mozart, 13009 Marseille, France, the
Department of
Nutritional Sciences, Rutgers University, New Brunswick, New Jersey
08901, and the § Department of Pediatrics, Division of
Developmental Biology and Nutrition, Georgetown University Medical
Center, Washington, D. C. 20007
In the human stomach, gastric lipase hydrolyzes
only 10 to 30% of ingested triacylglycerols because of an inhibition
process induced by the long chain free fatty acids generated, which are mostly protonated at gastric pH. The aim of this work was to elucidate the mechanisms by which free fatty acids inhibit further hydrolysis. In vitro experiments examined gastric lipolysis of
differently sized phospholipid-triolein emulsions by human gastric
juice or purified human gastric lipase, under close to physiological
conditions. The lipolysis process was further investigated by scanning
electron microscopy, and gastric lipase and free fatty acid movement
during lipolysis were followed by fluorescence microscopy. The results demonstrate that: 1) free fatty acids generated during lipolysis partition between the surface and core of lipid droplets with a molar
phase distribution coefficient of 7.4 at pH 5.40; 2) the long chain
free fatty acids have an inhibitory effect only when generated during
lipolysis; 3) inhibition of gastric lipolysis can be delayed by the use
of lipid emulsions composed of small-size lipid droplets; 4) the
release of free fatty acids during lipolysis induces a marked increase
in droplet surface area, leading to the formation of novel particles at
the lipid droplet surface; and 5) the gastric lipase is trapped in
these free fatty acid-rich particles during their formation. In
conclusion, we propose a model in which the sequential physicochemical
events occurring during gastric lipolysis lead to the inhibition of
further triacylglycerol lipolysis.
*
This work was supported in part by the Laphal Laboratory.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.