Lysine acetoacetylation

Amino acids that give rise to ketone bodies (acetylCoA or acetoacetyl-CoA, neither of which can bring about net glucose production) are called ketogenic amino acids. Leucine and lysine are ketogenic amino acids. Some amino acids, e.g. threonine, isoleucine, phenylalanine, tyrosine and tryptophan, can be both ketogenic and glycogenic. 

The seven amino acids that are degraded entirely or in part to acetoacetyl-CoA and/or acetyl-CoA—phenylalanine, tyrosine, isoleucine, leucine, tryptophan, threonine, and lysine—can yield ketone bodies in the liver,... 

Portions of the carbon skeletons of seven amino acids— tryptophan, lysine, phenylalanine, tyrosine, leucine, isoleucine, and threonine—yield acetyl-CoA and/or acetoacetyl-CoA, the latter being converted to acetyl-CoA (Fig. 18-21). Some of the final steps in the degrada-tive pathways for leucine, lysine, and tryptophan resemble steps in the oxidation of fatty acids. Threonine (not shown in Fig. 18-21) yields some acetyl-CoA via the minor pathway illustrated in Figure 18-19. 

The amino acids producing pyruvate are alanine, cysteine, glycine, serine, threonine, and tryptophan. Leucine, lysine, phenylalanine, and tryptophan yield acetyl-CoA via acetoacetyl-CoA. Isoleucine, leucine, threonine, and tryptophan also form acetyl-CoA directly. 

Lysine, an exclusively ketogenic amino acid, is unusual in that nei ther of its amino groups undergoes transamination as the first step in catabolism. Lysine is ultimately converted to acetoacetyl CoA. 

Amino acids whose catabolism yields either acetoacetate or one of its precursors, acetyl CoA or acetoacetyl CoA, are termed ketogenic. Tyrosine, phenylalanine, tryptophan, and isoleucine are both ketogenic and glucogenic. Leucine and lysine are solely ketogenic. 

Answer Lysine and leucine are exclusively ketogenic. These amino acids are degraded entirely to acetyl-CoA and acetoacetyl-CoA, and no parts of their carbon skeletons can be used for glucose synthesis. Leucine is especially common in proteins. Its degradation makes a substantial contribution to ketosis under starvation conditions. 

The catabolism of lysine merges with that of tryptophan at the level of (3-ketoadipic acid. Both metabolic pathways are identical from this point on and lead to the formation of acetoacetyl-CoA (Figure 20.21). Lysine is thus ketogenic. It does not transaminate in the classic way. Lysine is a precursor of carnitine the initial reaction involves the methylation of e-amino groups of protein-bound lysine with SAM. The N-methylated lysine is then released proteolytically and the reaction sequence to carnitine completed. See Equation (19.6) for the structure of carnitine. 

Leucine and lysine are purely ketogenic amino adds. The catabolism of these amino acids does not yield intermediates of the Krebs cycle. It does not yield pyruvate. It does not produce compoimds that can result in the net synthesis of glucose. Leucine catabolism results in the production of a molecule of acetyl-CoA and a molecule of acetoacetate lysine breakdown produces acetoacetyl-CoA. 

Lysine. Lysine is converted to a-ketoadipate in a series of reactions that include two oxidations, removal of the side chain amino group, and a transamination. Acetoacetyl-CoA is produced in a further series of reactions that involve several oxidations, a decarboxylation, and a hydration. Acetoacetyl-CoA can be converted to acetyl-CoA in a reaction that is the reverse of a step in ketone body formation. 

Although fatty acid oxidation is usually the major source of ketone bodies, they also can be generated from the catabolism of certain amino acids leucine, isoleucine, lysine, tryptophan, phenylalanine, and tyrosine. These amino acids are called keto-genic amino acids because their carbon skeleton is catabolized to acetyl CoA or acetoacetyl CoA, which may enter the pathway of ketone body synthesis in liver. Leucine and isoleucine also form acetyl CoA and acetoacetyl CoA in other tissues, as well as the liver. 

SOLUTION PROPERTIES OF IRON COMPLEXES OF ACETOACETYLATED POLY-L-LYSINE, POLY-L-ORNITHINE AND... 

Abstract Acetoacetylated poly-L-lysine (PALL), poly-L-ornithine (PALO) and poly-L-diaminobutyric acid (PADB) form coloured complexes with ferric ions. Investigations by several methods show that two j3-ketoamide side-chains are bound per metal ion in the range of pH 2-3. Under the same experimental conditions the model compound n-hexyl acetoacetamide forms a 1 1 complex with Fe III. The different behavior observed for the monomeric and the polymeric complexes both in the stoichiometry and in the position and intensities of the absorption bands has been attributed to steric relationships between the polypeptide side chains. 

The conformational properties of polypeptides containing j3-keto-amide groups in the side chain, such as acetoacetylated poly-L-lysine, poly-L-ornithine and poly-L-diaminobutyric acid, have been recently investigated in our laboratory [1 ]. 

The complexes formed between the ferric ion and the acetoacetylated polymers under the same solvent, pH, ionic strength and concentration conditions as for the model compound exhibit very similar spectral features with respect to each other. The poly-aceto-acetyl-L-lysine (PALL)-Fe complex is shown as very similar in Figure 2. It exhibits a maximum at 257 nm (molar extinction coefficient — 20 000) due to the tt tt transition of the enolate side chains and a second one centered at 478 nm (molar extinction coefficient — 1 500), which is attributed to the metal-ligand interactions in the polymeric complexes (the uncomplexed polymers exhibit in the UV region a maximum centered at — 256 nm with e of the order of 300). With the above analytical methods the metal-ligand ratio is found to be 1 2, i.e. two side chains are bound per metal ion and the binding constant can be evaluated as of the order of 10. Furthermore, by comparing the ab-... 

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