Quelques observations sur le mode d'action de la monoglycéride transacylase et de la diglycéride transacylase de la muqueuse intestinale

Abstract

The biosynthesis of lymphatic triglycerides from monoglycerides and acyl-CoA involves two transacylations. The purpose of this paper is to compare the action of the corresponding transacylases (monoglyceride transacylase and diglyceride transacylase) on the two positional isomers of their respective substrates (1- and 2-monoglycerides; 1,2- and 1,3-diglycerides). The enzyme preparation is a microsomal fraction of rat-intestinal mucosa. The experimental conditions are selected in such a way that spontaneous isomerizations of partial glycerides used as substrates or formed during the incubations are substantially avoided. Under these conditions, it is shown that:

• 1.

  1. 2-Monoglycerides from high amounts of 1,2-diglycerides and triglycerides, whereas 1-monoglycerides mainly form 1,3-diglycerides and very low quantities of triglycerides. This observation confirms that monoglyceride transacylase acts in vitro on both isomers of monoglycerides and that 1-monoglyceride acylation mainly occurs on the external carbon. Furthermore, it suggests that 2-monoglycerides formed by pancreatic lipase in the testinal lumen are more efficient acceptors for triglyceride biosynthesis than their isomers 1.

• 2.

  2. The first advantage of 2-monoglycerides over 1-monoglycerides is seen at the level of monoglyceride transacylase itself. Competition experiments show that there exists in rat mucosa a single monoglyceride transacylase acting on both isomers. The maximal velocity reached with both isomers is of the same order for a given concentration of acyl-CoA. But, the affinity of the enzyme and of the complez enzyme-acyl-CoA for 2-monoglycerides is definitely higher. Moreover, the ternary complex enzyme-acyl-CoA-monoglyceride breaks down more rapidly when the monoglyceride is the isomer 2. Since 2-monoglycerides are certainly more abundant in mucosa than 1-monoglycerides, these facts mean that the main reaction catalyzed by monoglyceride transacylase in vivo is the acylation of 2-monoglycerides into 1,2-diglycerides.

• 3.

  3. The second advantage is seen at the level of diglyceride transacylase which is distinct from monoglyceride transacylase in rat mucosa. In the presence of acyl-CoA 0.22 mM, the enzyme forms very little triglycerides from 1,3-diglycerides and high amounts from 1,2-diglycerides.

These results strongly suggest that the main pathway for triglyceride biosynthesis in intestinal mucosa is: 2-monoglycerides → 1,2-diglycerides → triglycerides.

This pathway provides a ready utilization of 2-monoglycerides formed by lipase in intestinal lumen and a junction point at the level of 1,2-diglycerides for the classical pathway starting from α-glycerophosphate. The role played by 2-monoglycerides in the biosynthesis process in vivo is proved in a fully independent way by the fact that most exogenouse lymphatic triglycerides have the same internal chain as the triglycerides ingested by animals. Lymphatic triglycerides are probably formed from α-glycerophosphate in animals ingesting free fatty acids.