Albumin fatty liver

The pharmacokinetics of PFOS and PFOA have been investigated in animal studies [22-24]. Results indicate that both PFCs are well absorbed following oral exposure, and poorly eliminated. In addition, PFOS and PFOA are very persistent as they are not metabolized and undergo extensive enterohepatic circulation [25,26]. PFSAs and PFCAs are unique among other persistent halogenated organic contaminants as they do not preferentially accumulate in fatty tissues, but instead are predominately distributed in the liver, serum and kidney [22-24]. This may be explained by the fact that PFOS and PFOA bind to proteins, specifically )8-lipoproteins, albumin and liver fatty acid-binding proteins [27, 28]. 

An elevation of ChE activity can be detected in fatty liver, obesity, diabetes mellitus, exudative enteropathy, nephrotic syndrome, hyperthyroidism, Meulengracht s icterus, chronic obstructive jaundice, etc. Specificity in liver diseases is 61%, and sensitivity is 49%. In cirrhosis, however, sensitivity is 88% normal ChE therefore widely excludes cirrhosis. In connection with other hepatobiliary enzymes, ChE can be useful in the diagnosis and assessment of the course of liver disease. There is a very good correlation of ChE activity with coagulation factors in liver diseases however, the correlation is less significant with albumin synthesis. 

Plasma P-lipoprotein concentration in rats receiving orotic acid falls to less than 1% of normal and rebounds to normal level within 48 hours following withdrawal of orotic acid [300]. When perfused in situ, the livers from orotic acid fed rats released a-lipoprotein, albumin, and other plasma proteins but no detectable p-lipoprotein. They also released smaller amounts of cholesterol and phospholipids than normal livers and no triglycerides, although they contained ten times the normal amount of triglycerides [300]. Since p-lipoprotein has a specific role in the normal transport of triglycerides, the fatty liver produced by orotic acid appears to result from the inhibition of synthesis or release of hepatic P-lipoprotein. 

Kwashiorkor— The specific features which distinguish this disorder from marasmus are (1) a significantly subnormal albumin concentration in plasma, (2) swollen parotid glands (just under and in front of the ears), (3) a depressed ratio of essential to nonessential amino acids in the blood plasma, (4) fatty liver (which often may be palpated, and (5) a moderate deficit in weight for height and age (the weight is usually 80% or more of normal). 

Acetoacetate and /3-hydroxybutyrate are transported through the blood from liver to target organs and tissues, where they are converted to acetyl-CoA (Figure 24.29). Ketone bodies are easily transportable forms of fatty acids that move through the circulatory system without the need for eomplexation with serum albumin and other fatty acid—binding proteins. 

Albumin is the most abundant (about 55%) of the plasma proteins. An important function of albumin is to bind with various molecules in the blood and serve as a carrier protein, transporting these substances throughout the circulation. Substances that bind with albumin include hormones amino acids fatty acids bile salts and vitamins. Albumin also serves as an osmotic regulator. Because capillary walls are impermeable to plasma proteins, these molecules exert a powerful osmotic force on water in the blood. In fact, the plasma colloid osmotic pressure exerted by plasma proteins is the only force that retains water within the vascular compartment and therefore maintains blood volume (see Chapter 15). Albumin is synthesized in the liver. 

Figure 13.2 Schematic representation of the creation of hPXR humanized mice. The humanization was achieved in the liver only when the liver-specific albumin promoter was used to direct the transgene expression, or in both the liver and the intestine when the fatty acid binding protein promoter was used. PCN, pregnenolone-16a-carbonitrile RIF, rifampicin. + and mean induction and lack of induction, respectively.

Albumin has a molecular mass of approximately 66 000 and is synthesized at a rate of about 12 g, equal to 3% of total body albumin, per day to replace that which is degraded or lost. Impaired albumin synthesis and therefore a low plasma albumin concentration, is a hallmark of chronic liver disease. Several functions can be ascribed to albumin including osmotic (oncotic) pressure regulation of the plasma and a non-specific transport protein for ligands such as calcium, fatty acids, drugs and bilirubin. 

Glycerol may be picked up by liver and converted to dihydroxyacetone phosphate (DHAP) for gluconeogenesis, and the fetty adds are distributed to tissues that can use them. Free fatty acids are transported through the blood in association with serum albumin. 

Long-chain fatty acid albumin bound adipose tissue liver, skeletal muscle, kidney. 

Medium-chain fatty acid albumin bound diet (especially dairy produce) cardiac muscle, liver... 

Acetoacetate and 3-hydroxybutyrate are known as ketone bodies. They are classified as fat fuels since they arise from the partial oxidation of fatty acids in the liver, from where they are released into the circulation and can be used by most if not all aerobic tissues (e.g. muscle, brain, kidney, mammary gland, small intestine) (Figure 7.7, Table 7.1). There are two important points (i) ketone bodies are used as fuel by the brain and small intestine, neither of which can use fatty acids (ii) ketone bodies are soluble in plasma so that they do not require albumin for transport in the blood. 

Lipid metabolism in the liver is closely linked to the carbohydrate and amino acid metabolism. When there is a good supply of nutrients in the resorptive (wellfed) state (see p. 308), the liver converts glucose via acetyl CoA into fatty acids. The liver can also take up fatty acids from chylomicrons, which are supplied by the intestine, or from fatty acid-albumin complexes (see p. 162). Fatty acids from both sources are converted into fats and phospholipids. Together with apoproteins, they are packed into very-low-density lipoproteins (VLDLs see p.278) and then released into the blood by exocytosis. The VLDLs supply extrahepatic tissue, particularly adipose tissue and muscle. 

As the fast progresses, more of the adipose-derived fatty acids are transported in the bloodstream as complexes with albumin and taken up by the liver. 

Short- and medium-chain length fatty acids are not converted to their CoA derivatives, and are not reesterified to 2-monoacylglyc-erol. Instead, they are released into the portal circulation, where they are carried by serum albumin to the liver.]... 

Fate of free fatty acids The free fatty acids derived from hydrolysis of triacylglycerol may directly enter adjacent mus cells or adipocytes. Alternatively, the free fatty acids may be tra ported in the blood in association with serum albumin until tt are taken up by cells. [Note Serum albumin is a large prot secreted by the liver. It transports a number of primarily hydropl bic compounds in the circulation, including free fatty acids a some drugs.2] Most cells can oxidize fatty acids to produ energy (see p. f88). Adipocytes can also reesterify free fa acids to produce triacylglycerol molecules, which are stored ui the fatty acids are needed by the body (see p. 185). 

Bile salts secreted into the intestine are efficiently reabsorbed (greater than 95 percent) and reused. The mixture of primary and secondary bile acids and bile salts is absorbed primarily in the ileum. They are actively transported from the intestinal mucosal cells into the portal blood, and are efficiently removed by the liver parenchymal cells. [Note Bile acids are hydrophobic and require a carrier in the portal blood. Albumin carries them in a noncovalent complex, just as it transports fatty acids in blood (see p. 179).] The liver converts both primary and secondary bile acids into bile salts by conjugation with glycine or taurine, and secretes them into the bile. The continuous process of secretion of bile salts into the bile, their passage through the duodenum where some are converted to bile acids, and their subsequent return to the liver as a mixture of bile acids and salts is termed the enterohepatic circulation (see Figure 18.11). Between 15 and 30 g of bile salts are secreted from the liver into the duodenum each day, yet only about 0.5 g is lost daily in the feces. Approximately 0.5 g per day is synthesized from cholesterol in the liver to replace the lost bile acids. Bile acid sequestrants, such as cholestyramine,2 bind bile acids in the gut, prevent their reabsorption, and so promote their excretion. They are used in the treatment of hypercholesterolemia because the removal of bile acids relieves the inhibition on bile acid synthesis in the liver, thereby diverting additional cholesterol into that pathway. [Note Dietary fiber also binds bile acids and increases their excretion.]... 

Fatty acids are carried by serum albumin to the liver and to peripheral tissues, where oxida tion of the lipids provides energy. (Cells, such as red blood cells, with few or no mitochondria cannot oxidize fatty acids, nor can the brain, because long-chain fatty acids do not cross the blood-brain barrier.)... 

CM and VLDL secreted by intestinal cells and VLDL synthesized and secreted in the liver have similar metabolic fates. After secretion into the blood, newly formed CM and VLDL take up apoprotein (apo-C) from HDL and are subsequently removed from the blood (plasma half-life of less than 1 h in humans [137]) primarily by the action of lipoprotein lipase (LPL). Lipoprotein lipase is situated mainly in the vascular bed of the heart, skeletal muscle, and adipose tissue and catalyzes the breakdown of core TG to monoglycerides and free fatty acids, which are taken up into adjacent cells or recirculated in blood bound to albumin. The activity of LPL in the heart and skeletal muscle is inversely correlated with its activity in adipose tissue and is regulated by various hormones. Thus, in the fasted state, TG in CM and VLDL is preferentially delivered to the heart and skeletal muscle under the influence of adrenaline and glucagon, whereas in the fed state, insulin enhances LPL activity in adipose tissue, resulting in preferential uptake of TG into adipose tissue for storage as fat. 

Weisiger R, Gollan J, Ockner R. 1981. Receptor for albumin on the liver cell surface may mediate uptake of fatty acids and other albumin-bound substances. Science 211 1048-1050. 

Artificial liver support systems aim at the extracorporeal removal of water soluble and protein-bound toxins (albumin being the preferential binding protein) associated with hepatic failure. Albumin contains reversible binding sites for substances such as fatty acids, hormones, enzymes, dyes, trace metals and drugs [26] and therefore helps elimination by kidneys of substances that are toxic in the unbound state. It should be noticed that the range of substances to be removed is broad and not completely identified. Clinical studies showed that the critical issue of the clinical syndrome in liver failure is the accumulation of toxins not cleared by the failing liver. Based on this hypothesis, the removal of lipophilic, albumin-bound substances, such as bilirubin, bile adds, metabolites of aromatic amino acids, medium-chain fatty acids, and cytokines, should be benefidal to the dinical course of a patient in liver failure. 

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