Transfer proteins microsomal lipid

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. 

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

Assembly of chylomicrons The enzymes involved in triacylglycerol, cholesterol, and phospholipid synthesis are located in Ihe smooth ER. Assembly of the apolipoproteins and lipid into chylomicrons requires microsomal triacylglycerol transfer protein (see p. 229), which loads apo B-48 with lipid. This occurs during transition from the ER to the Golgi, where the particles are packaged in secretory vesicles. These fuse with the plasma membrane releasing the lipoproteins, which then enter the lymphatic system and, ultimately, the blood. 

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. 

The transfer of phospholipids between mitochondria and microsomes in vitro was first used to measure the activity of lipid transfer proteins (Wirtz and Zilversmit, 1968). In this assay, isolated mitochondria and microsomes are incubated with an appropriate amount of transfer protein. Either particle may be radiolabeled and serve as the donor particle. The exchange reaction is terminated by sedimenting the mitochondria by centrifugation. The change in the radioactivity of either the donor or acceptor particles can be used to calculate the lipid transfer activity. 

The transbilayer movement of phospholipids in microsomal membranes has been measured using several different approaches. Phospholipid transfer proteins were used to probe the transbilayer movement of lipids in preparations of liver microsomes that were first radiolabeled with lipid precursors in vivo (D.B. Zilversmit, 1977). The results from these experiments provided evidence that PC, PE, PS, and PI from both membrane leaflets were exchanged between labeled microsomes and excess acceptor membranes with a maximal t 2 of 45 min. 

The common function of all apolipoproteins is to help solubilize neutral lipids in the circulation. The apolipoproteins bind readily to PL-water interfaces and, under appropriate conditions, can spontaneously form discrete particles with PL. In vivo, the assembly of apolipoproteins with lipids to form lipoproteins may require the assistance of cellular proteins such as the microsomal lipid transfer protein or the ABCAl transporter. 

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. 

Substances influencing drug and xenobiotic metabolism (other than enzyme inducers) include lipids, proteins, vitamins, and metals. Dietary lipid and protein deficiencies diminish microsomal drug-metabolizing activity. Protein deficiency leads to a reduction in hepatic microsomal protein and lipid deficiency oxidative metabolism is decreased because of an alteration in endoplasmic reticulum (ER) membrane permeability affecting electron transfer. In terms of toxicity, protein deficiency would increase the toxicity of drugs and xenobiotics by reducing their oxidative microsomal metabolism and clearance from the body. 

Gordon, D.A., Jamil, H., Gregg, R.E., Olofsson, S-O. Boren, J. (19%) J. Biol Chem., 271, 33047-33053. Inhibition of the microsomal triglyceride transfer protein blocks the first step of apolipoprotein B lipoprotein assembly but not the addition of bulk core lipids in the second step. 

Yamada et al. (1978) demonstrated again this transfer in the following way. Microsomes labeled with were prepared by feeding [ Cjacetate to endosperm tissue slices from 4-day-old castor bean seedlings and incubated with unlabeled mitochondria from the same tissues. The loss of C lipids from microsomes was accompanied by an increase in lipids in mitochondria. The addition of a 105,000-g supernatant, and a further pH 5.1-treated supernatant prepared from castor bean endosperms at the same stage, markedly enhanced the lipid transfer from microsomes to mitochondria. The activity of the added fraction was precipitated by ammonium sulfate and lost after pepsin or heat treatment. Thus it was concluded that in castor bean endosperms phospholipids were transferred from the endoplasmic reticulum to mitochondria and that this exchange was mediated by a protein contained in the cytosol. In castor bean tissues, the transfer of lipids was limited to phospholipids (Table III). 

The mechanisms involved in the establishment of lipid asymmetry are not well understood. The enzymes involved in the synthesis of phospholipids are located on the cytoplasmic side of microsomal membrane vesicles. Translocases (flippases) exist that transfer certain phospholipids (eg, phosphatidylcholine) from the inner to the outer leaflet. Specific proteins that preferentially bind individual phospholipids also appear to be... 

Helmkamp (1980a) studied the effect of the fatty acid composition of the acceptor lipid on the stimulation of phosphatidylinositol transfer from rat liver microsomes to phosphatidylcholine vesicles by bovine brain exchange protein. Acceptor vesicles containing egg phosphatidylcholine or dioleoyl phosphatidylcholine gave approximately the same transfer activity, whereas dielaidoyl phosphatidylcholine or dimyristoyl phosphatidylcholine vesicles produced lower transfer rates. Zborowski and Demel (1982) used the same protein and measured the rate of transfer of phosphatidylinositol from a monolayer to phosphatidylcholine vesicles. Vesicles of egg, dioleoyl, dielaidoyl, and dipalmitoyl phosphatidylcholine, even below its phase transition temperature, all gave equivalent transfer rates. However, a reduced rate was found when dimyristoyl and dilin-oleoyl phosphatidylcholine, and other phosphatidylcholines with two polyunsaturated fatty acids, were used. Table IV shows a comparison of the transfer activities measured in the two assays. The transfer rates are expressed as a percent of the transfer rate obtained with egg phosphatidylcholine acceptor vesicles. 

Characteristics of chemicals showing high transfer from maternal blood to placenta include low molecular weight (< 500 daltons optimal), high lipid/water partition coefficient (lipophilic), low ionization at blood pH (pKa) and low binding to plasma proteins ( ). The placenta contains a full complement of mixed function oxidases located in the microsomal and mitochondrial subcellular fractions capable of induction (eg. benzo(a)-pyrene hydroxylase, 24). 

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