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The pyruvate dehydrogenase complex that converts pyruvate to acetyl CoA in carbohydrate metabolism The -ketoglutarate dehydrogenase complex that converts -ketoglutarate to succinyl CoA in the Krebs cycle Enzymes involved in the metabolism of the branched chain amino acids leucine, isoleucine and valine The reduced form of lipoic acid, DHLA, also has the potential to act as an antioxidant It can interact directly with oxygen free radicals and can be involved in the regeneration of the reduced form of other antioxidants that have become oxidised such as vitamin C, vitamin E, glutathione and co-enzyme Q10 When it acts as a co-factor for enzymes it is covalently bound to the enzyme; the carboxyl group (COOH) of lipoic acid binds to the free amino group in the side chain of one of the enzyme s lysine residues to form lipoamide.

In the conversion of pyruvate to acetyl-CoA by pyruvate dehydrogenase, this lipoamide is converted to acetyl lipoamide in a complex reaction that also involves the co-factor thiamin pyrophosphate derived from vitamin B1 In this acetyl lipoamide one of the sulphur atoms is reduced by addition of hydrogen and the other is acetylated (it has an acetyl group derived from pyruvate attached to it) This acetyl lipoamide then reacts with reduced coenzyme to give acetyl-CoA and fully reduced dihydrolipoamide This dihydrolipoamide is normally re-oxidised by transfer of the hydrogen atoms attached to its sulphur atoms to NAD Rationale and evidence for the use of a-lipoic acid supplements When supplements of pure -lipoic acid are taken it is rapidly absorbed from the gut (perhaps a third of the total oral dose) and rapidly taken up by cells.

Within the cells -lipoic acid is converted to the reduced form DHLA which can act as an antioxidant but this is rapidly removed from cells and metabolised This suggests that any sustained antioxidant effect of lipoic acid would be more likely if the daily dose were split into several spaced aliquots -Lipoic acid is available on prescription in Germany for the treatment of diabetic neuropathy (peripheral nerve damage associated with diabetes) and has been widely used for this purpose there Diabetic neuropathy is one of a group of complications of diabetes that are associated with persistent hyperglycaemia including diabetic retinopathy (retinal degeneration), diabetic nephropathy (progressive loss of renal function) and cataract Better long-term glycaemic control is the primary focus of efforts to reduce these longterm complications (DCCT 1993).

Detailed discussion of the use of pharmacological doses for the treatment of diabetic neuropathy is beyond the scope of this book but data from these trials suggest that even large doses administered over a period of years appear to be well tolerated and no serious adverse consequences have been recorded This provides some reassurance about the use of smaller amounts as dietary supplements A review of the clinical trials of -lipoic acid for this purpose suggests that there is some preliminary evidential support for the belief that large supplements of -lipoic acid (at least 600 mg/day) have some bene cial effects upon the acute symptoms and progression of diabetic neuropathy (Ziegler et al 1999) Oxidative damage by free radicals is widely.

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Aside from helping you control the underlying coding method for producing layers, Dreamweaver enables you to define the default layer. This capability is especially useful during a major production effort in which the Web development team must produce hundreds of layers spread over a Web site. Being able to specify in advance the initial size, color, background, and visibility saves numerous steps each of which would have to be repeated for every layer. Figure 4-10 shows the layout of the Layers category of the Preferences dialog box.

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