Lipoic acid amide

Another result of the ring strain is that the reduction potential E° (pH 7, 25°C), is -0.30 V, almost the same as that of reduced NAD (-0.32V). Thus, reoxidation of reduced lipoic acid amide by NAD+ is thermodynamically feasible. Yet another property attributed to the ring strain in lipoic acid is the presence of an absorption maximum at 333 nm. 

Desulfurization of a number of thiols and disulfides, including the lipoic acid amide 174 under visible light irradiation, has received attention because of mild reaction conditions and the possibility to apply the same method in peptide chemistry (Scheme 23) <1999TA2643>. Accordingly, thioctic amide 174, that is, 5-(l,2-dithiolan-3-yl)pen-tanamide, was photochemically desulfurized in 36h in a one-pot reaction, giving 1-octanamide 175 in good yield. 

Abb. HSCoA = Coenzyme A GSH = Glutathione AM(D)(T)P = Adenosine mono (di)(tri)phosphate TPP = Thiamin pyrophosphate LipSj = Lipoic acid amide GD(T)P = Guanosine di(tri)phosphate K = Inorganic phosphate FAD(H2) = Enzyme-bound oxidized (reduced) Flavin-adenine-dinudeotide NAD (H) = Oxidized (reduced) Nicotinamide-adenine-dinucleotide. Compounds with are competitive inhibitors. 

LAA Lipoic acid amide. Acetaldehyde is dehydrogenated to the acetyl group on LAA. It is brought about by the transfer of acetaldehyde from TPP to LAA with accompanying reductive cleavage of the disulphide bridge. The newly formed bond is energy-rich. TPP is liberated. 

Lipoic acid exists as a mixture of two structures a closed-ring disulfide form and an open-chain reduced form (Figure 18.33). Oxidation-reduction cycles interconvert these two species. As is the case for biotin, lipoic acid does not often occur free in nature, but rather is covalently attached in amide linkage with lysine residues on enzymes. The enzyme that catalyzes the formation of the lipoamide nk.2Lg c requires ATP and produces lipoamide-enzyme conjugates, AMP, and pyrophosphate as products of the reaction. 

Lipoamide Lipoic acid is linked through an amide bond to a lysine residue in the enzyme... 

Figure 17-5. Oxidative decarboxylation of pyruvate by the pyruvate dehydrogenase complex. Lipoic acid is joined by an amide link to a lysine residue of the transacetylase component of the enzyme complex. It forms a long flexible arm, allowing the lipoic acid prosthetic group to rotate sequentially between the active sites of each of the enzymes of the complex. (NAD nicotinamide adenine dinucleotide FAD, flavin adenine dinucleotide TDP, thiamin diphosphate.)...

FIGURE 16-4 Lipoic acid (lipoate) in amide linkage with a Lys residue. The lipoyllysyl moiety is the prosthetic group of dihydrolipoyl transacetylase (E2 of the PDH complex). The lipoyl group occurs in oxidized (disulfide) and reduced (dithiol) forms and acts as a carrier of both hydrogen and an acetyl (or other acyl) group. 

While Tetrahymena must have lipoic acid in its diet, we humans can make our own, and it is not considered a vitamin. Lipoic acid is present in tissues in extraordinarily small amounts. Its major function is to participate in the oxidative decarboxylation of a-oxoacids but it also plays an essential role in glycine catabolism in the human body as well as in plants.295 296 The structure is simple, and the functional group is clearly the cyclic disulfide which swings on the end of a long arm. Like biotin, which is also present in tissues in very small amounts, lipoic acid is bound in covalent amide linkage to lysine side chains in active sites of enzymes 2963... 

Lipoic acid is often found near the active sites of enzymes, usually bound to the peptide by a long, flexible amide linkage with a lysine residue. 

Lipoic acid is quite a simple molecule with a cyclic disulfide as its main feature. It is attached to the enzyme as an amide with lysine. Our first concern will be with the much more complex coenzyme thiamine pyrophosphate. 

At the centre is enzyme 2 which binds the acetyl group through a lipoic acid-lysine amide. On the one side this acetyl group is delivered from pyruvate by the ministrations of thiamine pyrophosphate and enzyme T and on the other it is delivered to CoA as the free thiol ester. Enzyme 3 recycles... 

Biotin (6, Fig. 10) and lipoic acid (7, Fig. 1) are attached enzymatically to apoenzymes via carboxamide linkage to specific lysine residues (60, 61). The pantothenyl moiety (64, Fig. 7) can also be linked covalently to proteins via amide linkage (62). Covalently bound heme is involved in heme M (63) and heme L-catalyzed reactions (64, 65). 

Second, the hydroxyethyl group attached to TPP is oxidized to form an acetyl group and concomitantly Pansferred to lipoamide, a derivative of lipoic acid that is linked to the side chain of a lysine residue by an amide linkage. 

Ester and amide derivatives of lipoic acid (i.e., 360 and 361) are capable of increasing the rate of glucose transport in myotubes in culture in the absence or presence of insulin <2004BMC1183>. Due to the improved lipid solubility, these compounds surpass the potency of LA, which is used as an auxiliary drug for the treatment of diabetes, by a few orders of magnitude. 

Carboxylic acids and their derivatives appear to have fairly typical acid properties, for example, the amide (124) of lipoic acid can be dehydrated to a nitrile <86TL2203>. 

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