Sugar Alcohols Metabolism

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Sugar alcohols form as a result of enzymatic reduction of the respective mono- or disaccharides (A). The reduced form of glucose, sorbitol (also known as sorbit), plays a central role in this enzymatic reduction. Its formation is catalyzed by the same alcohol reduc-tase that reduces galactose to galactitol.

Sorbitol can be further metabolized to fructose (B); if there is excess fructose, this reaction may be reversed. Excess fructose also inhibits the conversion of sorbitol made from glucose to fructose, resulting in an accumulation of sorbitol. Aldol reductase and sorbitol dehydro-genase are present in all tissues, catalyzing the conversion from sorbitol to fructose and the reverse (C). In the Schwann cells of the peripheral nervous system, in the papillae of the kidneys, and in the epithelia of the eyes' lenses, there is intense aldol reductase activity. Aldol reductases are also common in the pancreatic islets of Langerhans; here, release of sorbitol is part of the signaling mechanism for insulin secretion.

Late complications of diabetes mellitus affect primarily the nervous system, pancreas, kidneys, and lenses. Due to the high level of aldol reductase activity, sorbitol can accumulate in these tissues if there is a sustained abundant supply of glucose (as from high fructose nutrition).

High concentrations of endogenous sugar alcohols in the tissues are linked to characteristic pathological changes. Especially with respect to diabetes mel-litus, the accumulation of endogenous sugar alcohols is being discussed as the pathogenic cause of secondary diseases of the nervous system, kidneys, and cardiovascular system. The mechanism at the root of these mostly degenerative processes is not yet known. An additional factor that might be involved here is nonenzymatic glyco-sylation of proteins, which can also be observed at elevated sugar alcohol levels. Nonenzymatic glycosylation of proteins also occurs when monosaccharide levels are permanently elevated. Since monosaccharides are bonded to peptide chains at random locations, this leads to abnormal glycoproteins (see p. 76).

The formation of excessive amounts of galactitol under high galactose conditions takes place in the same tissues where the sorbitol forms. It creates a particular problem since galactitol is not a suitable substrate for sorbitol de-hydrogenase and is therefore hard to remove.

Xylitol, supplied exogenously, is dehydrated to D-xylulose by cytoplasmic L-iditol dehydrogenase; the xylulose is phosphorylated to D-xylulose-5-phos-phate and can then enter the pentose phosphate cycle. The capacity for metabolizing xylitol of exogenous origin is much greater that the endogenous synthesis, which is limited by mitochondrial L-xylulose reductase.

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Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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