Fatty acid—albumin

The free fatty acid uptake by tissues is related directly to the plasma free fatty acid concentration, which in turn is determined by the rate of lipolysis in adipose tissue. After dissociation of the fatty acid-albumin complex at the plasma membrane, fatty acids bind to a membrane tty acid transport protein that acts as a transmembrane cotransporter with Na. On entering the cytosol, free fatty acids are bound by intracellular fatty acid-binding proteins. The role of these proteins in intracellular transport is thought to be similar to that of serum albumin in extracellular transport of long-chain fatty acids. 

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... 

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. 

Data presented in previous sections revealed that the concentration of FFAs in plasma may reach 2.0 mM during exercise. How is this possible when the highest attainable concentration in water is only about 0,1 mM This problem was resolved by nature by use of albumin as a vehicle for the transport of FFAs within the circulation. Albumin constitutes about 60% of the protein of blood plasma. It is a major carrier of FFAs, other metabolites, hormones, and drugs- Serum albumin has the capadty to carry several fatty adds. Figure 4.45 shows results from an experiment usingpurificdalbumin.Thenumberoffattyacid molecules bound per protein molecule is plotted versus the concentration of unbound fatty acids in solution. The study, conducted with lauric acid (12 carbons) and myristic add (14 carbons), demonstrates that one protein molecule is able to bind at least 8 or 9 molecules of fatty acid. Albumin has a molecular weight of 69 kDa and occurs in human plasma at a concentration of about 0.6 mM (40 mg/ml) (Halliwell, 1988). 

One of the smallest and the most abundant plasma proteins, albumin plays a significant role in osmotic regulation and transport of free fatty acids. Albumin is synthesized in the liver at a rate of approximately 14 g/d, or 10% of the total protein synthesis of the body. Deviations from the normal concentration of albumin in plasma can indicate the state of hepatic function. Albumin is also present in interstitial fluid. 

Glycerol Fatty acid-albumin (to the liver) complexes... 

The extreme hypoalbuminemia of the nephrotic syndrome can be attributed to the sustained urinary loss of albumin (S39), but it is doubtful whether albumin deficiency plays a causal role in the hyperlipemia and hypercholesterolemia found in this condition. Low-density lipoprotein (LDL) (90% lipids) is converted by lipoprotein lipase in vivo to high-density lipoprotein (HDL) (70% lipids), and the liberated fatty acid anions are bound and transported by plasma albumin. In normal nonlipemic serum the mean nonesterifled fatty acid/albumin molar ratio is 0.95 0.04, while in nephrotic sera—lipemic because of accumulation of LDL-triglycerides —the corresponding ratio is about 3 (C4). The plasma hyperlipemia which is observed in the nephrotic syndrome, and can be induced in rats by injections of antikidney serum, has been considered to result from albumin deficiency (R26). However this suggestion is not borne out by more recent studies (R25) and is contradicted by the failure of LDL to accumulate in the blood of analbuminic subjects (03). Plasma lipemia in the nephrotic syndrome apparently is due to loss or inhibition of lipoprotein lipase activity. 

C4. Chakravarti, B., and Scandrett, F., Observations on the non-esterified fatty acid-albumin ratio in some lipaemic conditions. Proc. Assoc. Clin. Biochem. 2, 15-16 (1962). 

The enzymes in the pathways of fatty acid activation and p-oxidation (the synthetases, the carnitine acyltransferases, and the dehydrogenases of p-oxidation) are somewhat specific for the length of the fatty acid carbon chain. The chain length specificity is divided into enzymes for long-chain fatty acids (C20 to approximately C12), medium-chain (approximately C12 to C4), and short-chain (C4-C2). The major lipids oxidized in the liver as fuels are the long-chain fatty acids (palmitic, stearic, and oleic acids), because these are the lipids that are synthesized in the liver, are the major lipids ingested from meat or dairy sources, and are the major form of fatty acids present in adipose tissue triacylglycerols. The liver, as well as many other tissues, uses fatty acids as fuels when the concentration of the fatty acid-albumin complex is increased in the blood. 

We have also performed some in vitro experiments with DHA. It was preincorporated into platelets after being precoated onto free fatty acid albumin. Under these conditions, most of the fatty acid was incorporated into phospholipids. Then platelets were rewashed and used for further experiments. The aggregability of DHA-rich... 

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