Microsomal triglyceride transfer protein

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The microsomal triglyceride transfer protein (MTP) is a protein complex made up of two proteins that is located in the endoplasmic reticulum (ER) of all mammals . MTP catalyzes the transport and incorporation of triglycerides , cholesterol esters , phospholipids and retinyl palmitate ( vitamin A ) from the ER lumen into those plasma lipoproteins that are associated with apolipoprotein  B (Apo B) (VLDL, IDL, LDL, chylomicrons ). MTP also participates in the recycling of the antigen-presenting glycoprotein CD1d in the lysosomes . In humans, MTP is mainly expressed in the liver and small intestine . Mutations in MTTP - gene coding for the large subunit encoded the complex can MTP deficiency and for this to hereditary hypo- or Abetalipoproteinemia lead.

The production of MTP in intestinal cells is stimulated by cholesterol , but slowed down by insulin . Another signaling pathway that influences MTP expression appears to be via the hormones leptin and melanocortin . Reduced expression of MTP was found in a mouse model of non-alcoholic steatohepatitis with insulin resistance .

structure

Surname gene Protein size
(aa)		 UniProt OMIM comment
MTP MTTP 876 P55157 157147 Abetalipoproteinemia , hypobetalipoproteinemia
PDI P4HB 491 P07237 176790 ubiquitous, multifunctional, EC  5.3.4.1

The second subunit is a protein disulfide isomerase which, when it participates in the post-translational modification of proteins , can act as a chaperone in high concentration . It is also a subunit of prolyl-4-hydroxylase .

Genetic defect

In the genetic defect of abetalipoproteinemia , the gene that codes for the microsomal triglyceride transfer protein is mutated. The MTP does not work properly in these patients. This permanently results in very low levels of apolipoprotein B and LDL.

Therapeutic MTP inhibition

The drug Lomitapid (trade name Lojuxta ® ) was introduced by the European Commission in 2012 and 2013 to accompany a low-fat diet and other lipid-lowering drugs with or without low-density lipoprotein apheresis (LDL apheresis) in adult patients with homozygous familial hypercholesterolemia authorized. Lomitapid is a selective inhibitor of microsomal transfer protein. The selective inhibition of MTP by lomitapid leads to a reduced formation of the lipid complexes Very Low Density Lipoprotein (VLDL) in the liver and chylomicrons in the intestine. As a result, less VLDL is released from the liver into the blood, or fewer chylomicrons are absorbed from the intestine. This results in a lowering of the blood levels of VLDL, LDL, LDL cholesterol, chylomicrons and Apo B.

Individual evidence

  1. ↑ Swiss Institute of Bioinformatics (SIB): PROSITE documentation PDOC51211. Retrieved September 20, 2011 .
  2. ↑ UniProt P55157
  3. ↑ Sagiv Y, Bai L, Wei DG, et al. : A distal effect of microsomal triglyceride transfer protein deficiency on the lysosomal recycling of CD1d . In: J. Med.. . 204, No. 4, April 2007, pp. 921-8. doi : 10.1084 / jem.20061568 . PMID 17403933 . PMC 2118556 (free full text).
  4. ↑ Jiao R, Guan L, Yang N, et al. : Frequent cholesterol intake up-regulates intestinal NPC1L1, ACAT2, and MTP . In: J. Agric. Food Chem . 58, No. 9, May 2010, pp. 5851-7. doi : 10.1021 / jf100879y . PMID 20405839 .
  5. ^ Iqbal J, Li X, Chang BH, et al. : An intrinsic gut leptin-melanocortin pathway modulates intestinal microsomal triglyceride transfer protein and lipid absorption . In: J. Lipid Res . 51, No. 7, July 2010, pp. 1929-42. doi : 10.1194 / jlr.M005744 . PMID 20164094 .
  6. ↑ Shindo N, Fujisawa T, Sugimoto K, et al. : Involvement of microsomal triglyceride transfer protein in nonalcoholic steatohepatitis in novel spontaneous mouse model . In: J. Hepatol. . 52, No. 6, June 2010, pp. 903-12. doi : 10.1016 / j.jhep.2009.12.033 . PMID 20392512 .
  7. ↑ UniProt P07237
  8. ↑ European Medicines Agency (EMA): Summary of Product Characteristics Lojuxta , accessed in September 2013.
  9. ↑ Hussain MM, Rava P, Walsh M. Multiple functions of microsomal triglyceride transfer protein. Nutrition & Metabolism 2012; 9:14

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