Fatty acids, long-chain, binding

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. 

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. 

Dutta-Roy, A.K. (2000) Cellular uptake of long chain fatty acids role of membrane associated fatty acid binding/transport proteins. Cellular and Molecular Life Sciences (in press). 

Harmon, C. M. and N. A. Abumrad. Binding of sulfosuccinimidyl fatty acids to adipocyte membrane proteins isolation and amino-terminal sequence of an 88-kD protein implicated in transport of long-chain fatty acids. J. Membr. Bid. 1993, 333, 43-49. 

Adrenoleukodystrophy is an X-linked dysmyelinative disorder caused by mutations in the ABCD1 gene, which encodes the peroxisomal integral membrane ALD protein, a member of the ATP binding cassette transporter family. These mutations result in impaired clearance of plasma very-long-chain fatty acids. Affected males may present with symmetrical distal axonal polyneuropathy, adrenocortical insufficiency or CNS demyelination, while occasional heterozygous women demonstrate deficits suggestive of multiple sclerosis [56]. Manipulation of dietary fatty acid intake has some minimal therapeutic effect, while bone marrow transplantation has diminished deficits in a few patients. (See in Ch. 41.)... 

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. 

Long-chain fatty acid binding to albumin a problem of transport, pathology and terminology... 

From Nocardia strains several closely related compounds (nocobactins, formo-bactin, amamistatins) were isolated that contain three typically Fe " binding sites, two hydroxamate units, and ahydroxyphenyloxazole stmcture (cf. Sect. 3.2 below). The C-terminus is A-hydroxy-cyc/o-Lys bound to a long chain 3-hydroxy fatty acid, whose hydroxy group is esterified by A -acyl-A -hydroxy-Lys, the a-amino group of which is bound to 2-o-hydroxyphenyl-5-methyl-oxazole-4-carboxylic acid (Table 4). For the amamistatins the configuration of the cyclic lysine was determined as L, the open one as d, and that of C-3 of the fatty acid as (S). The involvement in the iron metabolism was not investigated. 

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. 

The efficiency of the catalysis would also depend on the binding of the substrate to the piperazine-2,5-dione by means of weak forces. Imanishi and his group (85BCJ497) have sought to achieve this by means of hydrophobic interactions. They have chosen as substrates p-nitrophenyl esters of long-chain fatty acids the hydrocarbon chain would enter into... 

Abumrad N. A., El-Maghrabi M. R., Amri E., Lopez E. and Grimaldi P. (1993) Cloning of a rat adipocyte membrane protein implicated in binding or transport of long-chain fatty acids that is induced during preadipocyte differentiation. J. Biol. Chem. 268, 17665-17668. 

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