Transporter hepatic

Major physiological function Transports dietary triglyceride (Tg) from intestines to extrahepatic tissues (e.g., muscle, adipose tissue) Tg-depleted remnants deliver dietary cholesterol and some Tg to the liver Transports hepatic Tg to extrahepatic tissues converted into LDL Transports plasma cholesterol to liver and to extrahepatic tissues Takes up cholesterol from extrahepatic tissues and delivers it to liver, steroid-producing tissues, and other lipoproteins... 

VLDL provides a means of transporting triglyceride from the liver to the peripheral tissues while LDL transports hepatic cholesterol to the periphery. 

Electrotransport technology offers a number of benefits for therapeutic appHcations, including systemic or local adininistration of a wide variety of therapeutic agents with the potential adininistration of peptides and proteins long-term noninvasive administration, improving convenience and compliance controlled release, providing a desired deflvery profile over an extended period with rapid onset of efficacious plasma dmg levels and in some cases reduced side effects and a transport rate relatively independent of skin type or site. Additional benefits include easy inception and discontinuation of treatment, patterned and feedback-controlled deflvery, and avoidance of first-pass hepatic metaboHsm. 

Chandra P, Brouwer KL (2004) The complexities of hepatic dmg transport current knowledge and emerging concepts, Pharm Res 21 719-735... 

Dutartre H, Bussetta C, Boretto J, Canard B (2006) General catalytic deficiency of hepatitis C virus RNA polymerase with an S282T mutation and mutually exclusive resistance towards 2 -modified nucleotide analogues. Antimicrob Agents Chemother 50 4161 169 Elferink RO, Groen AK (2002) Genetic defects in hepatobiliary transport. Biochim Biophys Acta... 

Many of the phase 1 enzymes are located in hydrophobic membrane environments. In vertebrates, they are particularly associated with the endoplasmic reticulum of the liver, in keeping with their role in detoxication. Lipophilic xenobiotics are moved to the liver after absorption from the gut, notably in the hepatic portal system of mammals. Once absorbed into hepatocytes, they will diffuse, or be transported, to the hydrophobic endoplasmic reticulum. Within the endoplasmic reticulum, enzymes convert them to more polar metabolites, which tend to diffuse out of the membrane and into the cytosol. Either in the membrane, or more extensively in the cytosol, conjugases convert them into water-soluble conjugates that are ready for excretion. Phase 1 enzymes are located mainly in the endoplasmic reticulum, and phase 2 enzymes mainly in the cytosol. 

Tirona RG, Schwab AJ, Geng W, Pang KS. Hepatic clearance models comparison of the dispersion and Goresky models in outflow profiles from multiple indicator dilution rat liver studies. Drug Metab Dispos 1998 26 465-75. Bassingthwaighte JB, Sparks HV. Indicator dilution estimation of capillary endothelial transport. Anna Rev Physiol 1986 48 321-34. 

Water-soluble products of digestion are transported directly to the fiver via the hepatic portal vein. The fiver regulates die blood concentrations of glucose and amino acids. 

The digestible dietary carbohydrates yield glucose, galactose, and fructose that are transported via the hepatic portal vein to the hver where galactose and fructose are readily converted to glucose (Chapter 20). 

Figure 25-5. Metabolism of high-density lipoprotein (HDL) in reverse cholesteroi transport. (LCAT, lecithinxholesterol acyltransferase C, cholesterol CE, cholesteryl ester PL, phospholipid A-l, apolipoprotein A-l SR-Bl, scavenger receptor B1 ABC-1, ATP binding cassette transporter 1.) Prep-HDL, HDLj, HDL3—see Table 25-1. Surplus surface constituents from the action of lipoprotein lipase on chylomicrons and VLDL are another source of preP-HDL. Hepatic lipase activity is increased by androgens and decreased by estrogens, which may account for higher concentrations of plasma HDLj in women.

Figure 26-6. Transport of cholesterol between the tissues in humans. (C, unesterified choiesterol CE, cho-iesteryi ester TG, triacyigiyceroi VLDL, very iow density iipoprotein iDL, intermediate-density iipoprotein LDL, iow-density iipoprotein HDL, high-density iipoprotein ACAT, acyi-CoA choiesteroi acyitransferase LCAT, iecithinxhoiesteroi acyitransferase A-i, apoiipoprotein A-i CETP, choiesteryi ester transfer protein LPL, lipoprotein iipase HL, hepatic iipase LRP, LDL receptor-reiated protein.)...

Hepatic steatosis usually is a result of excessive administration of carbohydrates and/or lipids, but deficiencies of carnitine, choline, and essential fatty acids also may contribute. Hepatic steatosis can be minimized or reversed by avoiding overfeeding, especially from dextrose and lipids.35,38 Carnitine is an important amine that transports long-chain triglycerides into the mitochondria for oxidation, but carnitine deficiency in adults is extremely rare and is mostly a problem in premature infants and patients receiving chronic dialysis. Choline is an essential amine required for synthesis of cell membrane components such as phospholipids. Although a true choline deficiency is rare, preliminary studies of choline supplementation to adult patients PN caused reversal of steatosis. 

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