Fatty acids, long-chain, binding albumin

A. A. Bhattacharya, T. Grime, S. Curry, Crystallographic Analysis Reveals Common Modes of Binding of Medium and Long-Chain Fatty Acids to Human Serum Albumin , J. Mol. Biol. 2000, 303,121-132. 

Insulin detemir is a long-acting insulin analogue that lacks threonine at the B30 position and is acylated with a 14-carbon myristoyl fatty acid side-chain at the epsilon-amino group of the lysine in the B28 position. This stimulates binding to albumin and increases the half-life, extending its duration of action. 

Spector, A. A., John, K., and Fletcher, J. E., 1969, Binding of long-chain fatty acids to bovine serum albumin, J. Lipid Res. 10 56. 

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 binding to albumin a problem of transport, pathology and terminology... 

The most frequent protein in the plasma, at around 45 g is albumin. Due to its high concentration, it plays a crucial role in maintaining the blood s colloid osmotic pressure and represents an important amino acid reserve for the body. Albumin has binding sites for apolar substances and therefore functions as a transport protein for long-chain fatty acids, bilirubin, drugs, and some steroid hormones and vitamins. In addition, serum albumin binds Ca "" and Mg "" ions. It is the only important plasma protein that is not glycosylated. 

Figure 2.7. The complex pathways and processes involved in fat catabolism in vertebrate tissues such as cardiac and skeletal muscles. FFAs arrive at the cell boundary either via VLDL or albumin-associated and enter the cell either by simple diffusion or through transporters. In the cytosol, FFAs are bound by FABPs, which increase the rate and amount of FFA that can be transferred to sites of utilization. Shorter chain FFAs are converted to acetylCoA in peroxisomes longer chain FFAs are directly transferred to mitochondria (via a complex system involving acylcarnitines) as long-chain acylCoA derivatives these enter the /6-oxidation spiral and are released as acetylCoA for entrance into the Krebs or citric acid cycle in the mitochondrial matrix. Fatty acid receptors (FARs) in the nucleus bind to fatty acid response elements (FAREs) and in turn regulate the production of enzymes in their own metabolism. (Modified from Veerkamp and Maatman, 1995.)...

In contrast to cooperative binding, antagonistic binding has been proposed to explain why low concentrations of some analytes decreased the binding of others. An example is the inhibition of the interaction of chlorophenoxybu-tyrate with human serum albumin (HSA) caused by a low concentration of long-chain fatty acids [136]. 

The liver is the main origin of ketones in laboratory animals, where the long chain fatty acids are released from plasma albumin and bound to fatty acid-binding proteins in the hepatocytes. The long chain fatty acids react with CoA and then can be used to synthesize triacylglycerol or undergo beta-oxidation to acetyl CoA. When the levels of plasma fatty acids are elevated, acetyl CoA can be metabolized to form acetoacetate and 3-hydroxybutyrate or enter the tricarboxylic acid cycle. In ketosis, the levels of acetone, acetoacetate, and 3-hydroxybutyrate (also known as beta-hydroxybutyrate) are increased in both plasma and urine these three compounds historically were collectively called ketone bodies. Urine test strips can be used to test for ketonuria, and there are several enzymatic assays for 3-hydroxybutyrate and acetoacetate. 

During fasting and other conditions of metabolic need, long-chain fatty acids are released from adipose tissue triacylglycerols by lipases. They travel in the blood bound in the hydrophobic binding pocket of albumin, the major serum protein (see Fig. 23.1). 

Albumin is a protein polypeptide. Albumin has a molecular weight of 66.5 kDa and is the most abundant plasma protein, which is present in the concentration of 35-50 g/L in human serum and is synthesized in the liver. Human serum albumin (HSA) has a half-life of 19 days. It acts as a solubilizing agent for long chain fatty acids and is therefore essential for the transport and metabolism of lipids. It binds very well to penicillins, sulfonamides, indole compounds, benzodiazepines, copper, and nickel in a specific and calcium and zinc in a relatively nonspecific manner. It is responsible for osmotic pressure of the blood. 

A protein having a molecular weight of approximately 65 000. It has a transport role in the blood since it can reversibly bind long chain fatty acids, bilirubin, calcium and certain hormones, e.g. thyroxine and cortisol. In addition to its transport functions it can serve as a reserve store of protein and contributes significantly to plasma colloidal osmotic pressure. Two congenital disorders of albumin synthesis have been described, analbuminaemia when there is deficient synthesis, and bisalbuminaemia when two types of albumin occur. 

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