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Absorption and distribution

L-isoleucine is an essential α-amino acid, indicating that humans cannot synthesize it. Therefore, mammals must ingest it. High levels of L-isoleucine can be found in eggs, soy protein, seaweed, turkey, chicken, lamb, cheese, and fish.

L-isoleucine is an isomer of L-leucine, differing in the position of the side chain. In L-isoleucine, the methyl group is on the β-carbon of the amino acid chain, rather than the γ-carbon as in L-leucine.

L-isoleucine is biosynthesized in plants (Kirma et al, 2012, Journal of Experimental Botany, 63 (14), 4995-5001) and microorganisms (Park and Lee, 2010, Biotechnol J, 5, 560-577). In bacteria, L-Isoleucine is biosynthesized from threonine through the formation of α-ketobutyrate (Stryer and Freeman, 1988,Biochemistry, New York; Devlin and Wiley-Liss, 2002, Textbook of Biochemistry with Clinical Correlations, New York) The synthesis occurs in several steps, starting from pyruvic acid and α-ketoglutarate.

 

Preliminary predictions of adsorption of a substance can be made from its physico-chemical properties. Since the Log Kow is -1.72 and the water solubility is > 34 g/L, L-isoleucine is clearly very soluble in water.

Regarding inhalation, the combination of low volatility, a negative Log Kow and high water solubility suggests that absorption directly across the respiratory tract epithelium is unlikely.

Oral absorption is very favourable for L-isoleucine since the substance has a low molecular weight and is very soluble in water. L-isoleucine will readily dissolve in the gastrointestinal fluids and absorption can occur along the entire gastrointestinal tract and will be high.

Dermal absorption is unlikely because the poor lipophilicity suggests that substance is not likely to cross the stratum corneum. Moreover, the low volatility in combination with the high water solubility and the negative Log P value indicate that the substance may be too hydrophilic to cross the lipid rich stratum corneum and thus dermal uptake will be unlikely. (Nielsen et al., 2010, Informa Healthcare, Telephone House, London, UK)

 

 

Metabolism

As described above, L-isoleucine is absorbed from the gastrointestinal tract. Although much of the catabolism of amino acids takes place in the liver, isoleucine is oxidized as fuels primarily in muscle, adipose, kidney, and brain tissue. These extrahepatic tissues contain an aminotransferase that is absent in liver. The enzyme convers L-isoleucine to its correspondingα-ketoacid which will be decarboxylated, releasing the carboxyl group as CO2 and producing the acyl-CoA derivation. Experiments with rats have shown that the branched-chain α-ketoacid dehydrogenase complex is regulated by covalent modification in response to the content of branched-chain amino acids in the diet. (Nelson and Cox, 2005, Lehninger, New York; Salway, 2004, Blackwell Science Ltd, Alden, Mass)

 

Isoleucine provides a source of nitrogen for transport to the liver and kidney. (Stryer and Freeman, 1988, Biochemistry, New York; Devlin and Wiley-Liss, 2002, Textbook of Biochemistry with Clinical Correlations, New York)

 

L-isoleucine has a critical role as substrates for protein synthesis, however, it also plays other roles in the body as one of the branched chain amino acids (BCAAs). It is believed that it contribute to energy metabolism during exercise as energy sources and substrates to expand the pool of citric acid cycle intermediates and for gluconeogenesis (Yoshizawa, 2012, J Pharmacol Sci, 118, 149-155). Moreover, it serve as regulatory (signaling) molecules modulating protein synthesis. L-isoleucine also acts as a nutrient regulator of glucose metabolism. More specific, isoleucine administration stimulates both glucose uptake in the muscle and whole body glucose oxidation, in addition to depressing gluconeogenesis in the liver, thereby leading to a hypoglycemic effect in rats (Doi et al, 2005,J Nutr, 135, 2103–2108: Doi et al, 2007, Am J Physiol Endocrinol Metab, 292, E1683–E1693).

 

Portions of the carbon skeletons of isoleucine yield acetyl-CoA, the latter being converted to acetyl- CoA. Isoleucine contributes in this way to pyruvate or citric acid cycle intermediates. L-isoleucine can also be converted tosuccinyl –CoA and in this way enter the citric acid cycle(Nelson and Cox, 2005, Lehninger, New York; Salway, 2004, Blackwell Science Ltd, Alden, Mass).

 

 

Excretion

Catabolism of amino acids is particularly critical to the survival of animals with high-protein diets or during starvation. L-isoleucine is degraded to acetyl-CoA. In the liver the latter can be used to yield ketone bodies, making L-isoleucine a ketogenic amino acids. L-isoleucine can also be degraded to succinyl-CoA and thus converted to glucose and glycogen. Indicating that it is also a glucogenic amino acid. Succinyl-CoA is an intermediate of the citric acid cycle. Isoleucine undergoes transamination, followed by oxidative decarboxylation of the resultingα-keto acid. The remaining five-carbon skeleton is further oxidized to acetyl-CoA and propionyl-CoA. The end product can further be processed and enter the urea cycle and in this way bevexcreted as urea in the urine.(Nelson and Cox, 2005, Lehninger, New York; Salway, 2004, Blackwell Science Ltd, Alden, Mass)