Microsomal triglyceride transfer protein

Microsomal triglyceride transfer protein large subunit is a protein that in humans is encoded by the MTTP, also known as MTP, gene.

MTTP encodes the large subunit of the heterodimeric microsomal triglyceride transfer protein (MTP). Protein disulfide isomerase (PDI) completes the heterodimeric MTP, which has been shown to play a central role in lipoprotein assembly. Mutations in MTTP can cause abetalipoproteinemia.

Apolipoprotein B48 on chylomicra and Apolipoprotein B100 on LDL, IDL, and VLDL are important for MTP binding.

MTP adds triglycerides to nascent chylomicrons in the intestine, and to VLDL in the liver.

Structure
The large subunit of MTP, also known as the alpha subunit, contains an N-terminal half beta barrel, an alpha helix and a C-terminal lipid binding site that lies between two beta pleated sheets. It is a member of the large lipid transfer protein family, like apolipoprotein B (apo B), with which it interacts, but unlike apo B, it is not secreted. The heterodimer is instead retained in the endoplasmic reticulum due to the presence of a C-terminal KDEL motif on the PDI beta subunit.

Pharmacology
Drugs that inhibit MTTP prevent the assembly of apo B-containing lipoproteins thus inhibiting the synthesis of chylomicrons and VLDL and leading to decrease in plasma levels of LDL-C.
 * Lomitapide (Juxtapid) was approved by the US FDA for adjunctive treatment of homozygous familial hypercholesterolemia.
 * Dirlotapide (Slentrol) and mitratapide (Yarvitan) are veterinary drugs for the management of obesity in dogs.