Microsomal triglyceride transfer

Hoen P.A. C., Prince P., Van der Bilt E., Valentijn A. R., Meeuwenoord N.J., Princen H., Bijsterbosch M.K., van der Marel G.A., van Boom J.H., van BerkelT.J.C. Design of a targeted peptide nucleic acid prodrug to inhibit hepatic human microsomal triglyceride transfer protein expression in hepato-cytes. Bioconjug. Chem. 2002 13 295-302. 

Li, CM, Presley, B, Zhang, XM, Dashti, N, Chung, BH, Medeiros, NE, Guidry, C, and Curcio, CA, 2005. Retina expresses microsomal triglyceride transfer protein Implications for age-related maculopathy. J Lipid Res 46, 628-640. 

Microsomal triglyceride-transfer protein (MTP) plays a pivotal role in the assembly of TG-rich apolipoprotein B-containing VLDL in the liver and... 

Hussain MM, Shi J, Dreizen P (2003) Microsomal triglyceride transfer protein and its role in apoB-lipoprotein assembly. J Lipid Res 44 22-32... 

Lipoprotein Assembly and Microsomal Triglyceride Transfer Protein... 

In ABL, an early step in apoB lipoprotein assembly shared by intestinal and liver cells is defective. The net result is near absence of all plasma apoB lipoproteins. ApoB synthesis from a mRNA transcript occurs, but its successful assembly into the mature lipoprotein particle does not. The inability to assemble apoB into lipoproteins was shown to be due to a defect in the mttp gene in affected individuals (Wetterau et al., 1992). Its translational product is an 894-amino acid, 97-kd, polypeptide that exists in the ER complexed with a 55-kd protein disulfide isomerase which is believed to maintain solubility, physiologic activity, and ER retention of the 97-kd peptide. The heterodimeric complex of the 97-kd and 55-kd subunits is referred to as microsomal triglyceride transfer protein (MTP) (Wetterau et al., 1992). 

Berriot-Varoqueaux N, Aggerbeck LP, et al. The role of the microsomal triglyceride transfer protein in abetalipoproteinemia. Annu Rev Nut. 20 663-697, 2000. 

Wetterau JR, Aggerbeck I.p Bouma M, et al. Absence of microsomal triglyceride transfer protein in individuals with abetalipoproteinemia. Science 258 999-1001,1992. 

AUister, E. M., Borradaile, N. M., Edwards, J. Y., Huff, M. W. (2005). Inhibition of microsomal triglyceride transfer protein expression and apolipoprotein BlOO secretion by the citms flavonoid naiingenin and by insulin involves activation of the mitogen-activated protein kinase pathway in hepatocytes. Diabetes, 54, 1676-1683. 

Casaschi, A., Wang, Q., Dang, K., Richards, A., Theriault, A. (2002). Intestinal apoUpoprotein B secretion is inhibited by the flavonoid quercetin potential role of microsomal triglyceride transfer protein and diacylglycerol acyltransferase. Lipids, 37, 647-652. 

MSH-R, melanoc5de stimulating hormone receptor MTP, microsomal triglyceride transfer protein NEFA, non-esterified fatty acids NO, nitric oxide NPY, neuropeptide Y... 

In this autosomal recessive disease, the disorder does not involve the gene on chromosome 2, which is responsible for apoprotein assembly, but the MTP gene (microsomal triglyceride transfer protein), which is localized on chromosome 4 q 22—24. In the endoplasmic reticulum, MTP transfers cholesterol esters, triglycerides and phospholipids to the nascent apoprotein B. This process is a prerequisite for the transport of the complete lipoproteins (e.g. chylomicrons, VLDL) to the Golgi complex and their secretion into the blood via subsequent exocytosis. In the case of MTP deficiency, lipoprotein particles are not secreted, with the result that any superfluous apoprotein B is broken down in the endoplasmic reticulum. (214, 216, 219, 220)... 

Wetterau, J.R., Aggerbeck, L.P., Bouma, M.E., Esenberg, C, Munck, A., Hermier, M., Gay, G., Rader, D.J., Gregg, R.E Absence of microsomal triglyceride transfer protein in individuals with abetalipopro-teinemia. Science 1992 258 999-1001... 

L. B. Nielsen, M. Veniant, and J. Boren, et ah, Genes for apolipoprotein B and microsomal triglyceride transfer protein are expressed in the heart evidence that the heart has the capacity to synthesize and secrete lipoproteins, Circulation, 1998, 98, 13-16. 

Sharp, D., et al. 1993. Cloning and gene defects in microsomal triglyceride transfer protein associated with a beta lipoproteinaemia. Nature 365(6441) 65-69. 

Without the enzyme microsomal triglyceride transfer protein (MTP), hepatic triglycerides cannot be transferred to apoB-100. Patients with dysfunctional MTP fail to make any of the apoB-containing lipoproteins (VLDL, IDL, or LDL). MTP also plays a key role in the synthesis of chylomicrons in the intestine, and mutations of MTP that result in the inability of triglycerides to he transferred to either apoB-100 in the liver or apoB-48 in the intestine prevent VLDL and chylomicron production and cause the genetic disorder abetalipoproteinemia. 

F. 32.14. A model of microsomal triglyceride transfer protein (MTP) action. MTP is required to transfer hpid to apoB-48 as it is synthesized, and to transfer lipid from the cytoplasm to the ER lumen. 

Abetalipoproteinemia, which is due to a lack of MTP (microsomal triglyceride transfer protein see Chapter 32) activity, results in an inability to assemble both chylomicrons in the intestine and VLDL particles in the liver. 

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