Acid, dihydrolipoic

Gorecki, M., and Patchornik, A. (1973) Polymer-bound dihydrolipoic acid a new insoluble reducing agent for disulfides. Biochim. Biophys. Acta 303, 36-43. 

Podhradsky, D., Drobnica, L., and Kristian, P. (1979) Reactions of cysteine, its derivatives, glutathione, coenzyme A, and dihydrolipoic acid with isothiocyanates. Experientia 35, 154. 

DFO, desferrioxamine Dfx, desulfoferrodoxin DHA, docosahexaenoic acid DHE, dihydroethidium DHLA, dihydrolipoic acid DHR, dihydrorhodamine 123... 

Lipoic acid (the other names are a-lipoic acid or thioctic acid) (Figure 29.9) is a natural compound, which presents in most kinds of cells. Lipoic acid (LA) is contained in many food products, in particular in meat, but it is also synthesized in human organism from fatty acids. Earlier, it has been shown that in humans lipoic acid functions as a component of the pyruvate dehydrogenase complex. However, later on, attention has been drawn to the possible antioxidant activity of the reduced form of lipoic acid, dihydrolipoic acid (DHLA) (Figure 29.9). 

Quantum clusters are highly photostable when compared with organic fluorophores. A study was conducted to check the photostability of clusters in comparison to organic fluorophores and semiconductor quantum dots [12]. Photostability of a gold cluster capped with dihydrolipoic acid (AuNC DHLA) was compared with polymer coated CdSe/ZnS semiconductor quantum dots and two different organic fluorophores namely fluorescein and rhodamine 6G (Fig. 5). For the study, 20 pi of fluorescent AuNC DHLA was dissolved in sodium borate buffer of pH 9. The sample was loaded into a quartz cuvette and was exposed to blue-light (480 nm)... 

The system lipoic-dihydrolipoic acid behaves in a similar way. 

We have shown in the past few years that due to their finite size (comparable to an average protein), CdSe-ZnS core-shell nanocrystals capped with a thin layer of dihydrolipoic acid ligands provide excellent nanoscale scaffolds ( nanoscaffolds ) for attaching several proteins on their surfaces. QD-protein conjugates were used to design multiplexed immunoassays to detect soluble toxins. 

U.S.) Defense Advanced Projects Agency Dihydrolipoic acid (U.S.) Department of Defense (U.S.) Department of Energy (U.S.) Department of Transportation Differential reflectrometry = differential reflection spectrometry... 

Lactic acid bacteria such as Lactobacillus leichmanni and many other bacteria utilize a 5 -deoxyadenosylcobal-amin-containing enzyme to reduce nucleoside triphosphates according to Eq. 16-21. Thioredoxin or dihydrolipoic acid can serve as the hydrogen donor. Early experiments showed that protons from water are reversibly incorporated at C-2 of the reduced... 

Reaction of the reductase with dihydrolipoic acid in the presence of deoxy-GTP, which apparently serves as an allosteric activator, leads to formation, within a few milliseconds, of a radical with a characteristic EPR spectrum that can be studied when the reaction mixture is rapidly cooled to 130°K. When GTP (a true substrate) is used instead of dGTP, the radical signal reaches a maximum in about 20 ms and then decays. Of the various oxidation states of cobalt (3+, 2+, and 1+)... 

The chemical aspect of the coenzymatic action of a-lipoic acid is to mediate the transfer of electrons and acti-vated acyl groups resulting from the decarboxylation and oxidation of a-keto acids within the complexes. In this process, lipoic acid is itself transiently reduced to dihydrolipoic acid (see fig. 10.12), and this reduced form is the acceptor of the activated acyl groups. Its dual role of electron and acyl-group acceptor enables lipoic acid to couple the two processes. 

Spuches, A.M., Kruszyna, H.G., Rich, A.M. and Wilcox, D.E. (2005) Thermodynamics of the As(III)-thiol interaction arsenite and monomethylarsenite complexes with glutathione, dihydrolipoic acid, and other thiol ligands. Inorganic... 

In its reduced form, a-lipoic acid (Fig. 9.5) is a powerful antioxidant. It can reduce GSSG to GSH, dehydroascorbate to ascorbate, and regenerate a-tocopherol from the cy-tocopheryl radical either directly or via ascorbate. Supplementation with a-lipoic acid decreases oxidative stress and restores reduced levels of other antioxidants in vivo. However, a-lipoic acid and dihydrolipoic acid may exert pro-oxidant properties in vitro. a-Lipoic acid and dihydrolipoic acid promote the permeability... 

Moini H., Packer L., and Saris N. E. (2002). Antioxidant and prooxidant activities of -lipoic acid and dihydrolipoic acid. Toxicol. Appl. Pharmacol. 182 84-90. 

Lewisite is the most important of the organo-arseni-cal CW agents. Exposure to lewisite is quite painful, and onset of symptoms occurs rapidly (seconds to minutes) (31) in contrast to sulfur mustard for which a latency period occurs of several hours between exposure and symptoms (32). Although it is not known to have been used as a CW agent, lewisite is still considered a potential threat due to the relative ease of production and its rapid onset of action. Moreover, substantial stockpiles of lewisite are present in the United States, Russia, and in China abandoned by the Japanese Imperial Army. This may constitute a potential hazard for public health (33). The toxicity of lewisite is inter alia caused by the high affinity for the vicinal di-thiol system present in dihydrolipoic acid, a component of the pyruvate dehydrogenase complex, as is the case for other arsenicals (34). This prevents the formation of acetyl coenzyme A from pyruvate. 

Pyruvate produced by the glycolytic pathway may be transported into the mitochondria (via an antiport with OH"), where it is converted to acetyl-CoA by the action of the enzyme complex pyruvate dehydrogenase. The pertinent enzyme activities are pyruvate dehydrogenase (PD), lipoic acid acetyltransferase, and dihydrolipoic acid dehydrogenase. In addition, several cofactors are utilized thiamine pyrophosphate (TPP), lipoic acid, NAD+, Co A, and FAD. Only Co A and NAD+ are used in stoichiometric amounts, whereas the others are required in catalytic amounts. Arsenite and Hg2+ are inhibitors of this system. The overall reaction sequence may be represented by Figure 18.5. The NADH generated may enter the oxidative phosphorylation pathway to generate three ATP molecules per NADH molecule reduced. The reaction is practically irreversible its AGq = -9.4 kcal/mol. 

Radabaugh, T.R., Sampayo-Reyes, A., Zakharyan, R.A., Aposhian, H.V. (2002). Arsenate reductase II. Purine nucleotide phosphorylase in the presence of dihydrolipoic acid is a route for reduction of arsenate to arsenite in mammalian systems. Chem. Res. Toxicol. 15 692-8. 

In addition, CS reacts with the disulfhydryl form of lipoic acid, a coenzyme in the pyravate decarboxylase system (Olajos and Salem, 2001). Alteration in dihydrolipoic acid biochemistry can lead to decreased acetyl CoA levels, resulting in cellular injury. Therefore, tissue injury seems to be related to inactivation of these metabolic enzyme systems. The damage is transient because the enzymes can be rapidly reactivated if exposure is terminated (Beswick, 1983). 

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