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MTP
The microsomal triglyceride transfer protein (MTP) is a key protein in the assembly and secretion of apolipoprotein (apo) B-containing lipoproteins in the liver and intestine. Mutations in the gene encoding for MTP (MTTP) are the molecular basis of abetalipoproteinemia, a rare autosomal recessive disorder characterized by the absence of circulating apoB-containing lipoproteins of both intestinal and hepatic origin. MTP was soon found to consist of 2 subunits. The first is the unique MTP subunit, which in humans is 894 amino acids (97 kDa) and expressed primarily in hepatocytes and enterocytes. The second subunit is the ubiquitously expressed multifunctional protein disulfide isomerase (PDI; 55 kDa). MTP is responsible for transferring neutral lipids, mainly triglycerides, and phospholipids onto the assembling chylomicron and VLDL particles in the intestine and the liver, respectively. MTP inhibition is accompanied by gastrointestinal adverse events and increase in liver fat content that limit the broad use of this therapeutic approach.
The promoter region of MTTP contains cis-elements to which several transcription factors involved in the regulation of MTP expression bind. Fox and hepatic nuclear factors hepatocyte nuclear factor 1 and hepatocyte nuclear factor 4 are positive regulatory elements, whereas the sterol and insulin response elements may be negative. MTP is negatively regulated by bile acids via the nuclear receptor hepatocyte nuclear factor 4. MTTP gene transcription was high at night and low during the day; these variations might contribute to daily variation in plasma lipid and lipoprotein concentrations. This could affect hepatic cholesterol content, which in turn may relate to diurnal variation of hepatic cholesterol synthesis and proprotein convertase subtilisin kexin type 9 (PCSK9).
References
1.Hooper AJ, et al. Circ Res. 2015;116(1):193–205.
The promoter region of MTTP contains cis-elements to which several transcription factors involved in the regulation of MTP expression bind. Fox and hepatic nuclear factors hepatocyte nuclear factor 1 and hepatocyte nuclear factor 4 are positive regulatory elements, whereas the sterol and insulin response elements may be negative. MTP is negatively regulated by bile acids via the nuclear receptor hepatocyte nuclear factor 4. MTTP gene transcription was high at night and low during the day; these variations might contribute to daily variation in plasma lipid and lipoprotein concentrations. This could affect hepatic cholesterol content, which in turn may relate to diurnal variation of hepatic cholesterol synthesis and proprotein convertase subtilisin kexin type 9 (PCSK9).
References
1.Hooper AJ, et al. Circ Res. 2015;116(1):193–205.
Membrane Transporter/Ion Channel
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