METABOLISM OF DI- AND MONOSACCHARIDES 133

Percentage 150

100

1920 -OiC -96C

FIG. 1. Changes in the consumption of carbohydrates (CHO) over decades in the USA, repre- sentative of the general trends in the Western World. The bars refer to percent change in the mean intake of CHO. taking the year 1910 as 100% for each component. The lower part of the bars indicates the decrease in the consumption of the high molecular, complex CHO in 1980 to 57% of the 1910 value. The middle portion of the bar shows the proportion of the total CHO in the diet, the balance being filled by proteins and fats. The upper portion of the bars depicts the steady rise in the per- centage of the low molecular, simple, refined sugars by 30% from 1910 through 1980, almost all due to the rise in sucrose use. This rise appears to stabilize during the last decade at -135% of the 1910 value. Note that the data for 1960 represent the period of World War II and the postwar years. Adapted from Woteki CE. et al. (15). sue lesions, behavioral changes, decreased fertility, and increased mortality in an- imals (16.17). Fructose is now available directly in corn syrup, which is used ex- tensively as a food and beverage sweetener and is less expensive than sucrose. Hence, there is a renewed interest in the metabolism of fructose, especially at the high levels of intake at which deleterious changes may appear.

SPECIFIC DIFFERENCES IN METABOLISM OF FRUCTOSE AND GLUCOSE

The metabolism of fructose follows a pathway distinct from that of glucose because of an important structural difference: fructose is a 2-ketohexose, metabolized mainly in the liver, whereas glucose is an aldohexose capable of uptake by all body tissues. Thus, fructose constitutes a metabolic load targeted on the liver, whereas only a fraction of glucose (30-40%, depending on species and intake size) is processed directly in the liver. Fructolysis starts by phosphorylation of the hydroxyl group at carbon 1 to fructose 1-phosphate (F1P) by a specific hepatic fructokinase, whereas glycolysis commences by phosphorylation at carbon 6 to glucose 6-phosphate (G6P) by several less specific hexokinases present in all body tissues. It is biochemically feasible that hexokinases may phosphorylate some fructose to F6P, but this reaction is minimal in the competitive presence of ambient glucose concentration and the high Km of hexokinases toward fructose. k A further aspect favoring fructose metabolism in the liver is the high activity of fructokinase relative to that of enzymes phosphorylating glucose. This is a surprising mammalian characteristic, since glucose from exogenous and endogenous sources,