Fructose and glucose have the same caloric value, but the two sugars are metabolized differently. It emerges that mice that cannot metabolize fructose are healthier when placed on carbohydrate-rich diets.
A drastic increase in dietary sugar consumption in the western world during the past four decades has been paralleled by epidemics of obesity and metabolic syndrome, suggesting a cause-and-effect relationship. Yet the relative contribution of individual sugars — as opposed to total caloric intake — to this epidemic remains controversial. For instance, increased intake of fructose, which is enriched in soft drinks and processed foods, has been proposed to greatly contribute to these disorders. However, this proposal has not been universally embraced.
Dietary sugar encompasses several carbohydrates. Most often, however, it describes starch, sucrose and high-fructose corn syrup, each of which is composed of glucose with or without fructose: starch, found in bread and rice, is a glucose polymer; sucrose (table sugar) is a disaccharide made up of glucose and fructose; and high-fructose corn syrup, a common constituent of soft drinks, is a mixture of approximately 40% glucose and 60% fructose. From an energetic standpoint, a molecule of glucose has the same caloric value as a molecule of fructose. However, the human body treats these carbohydrates quite differently, raising questions about their individual roles in obesity and metabolic syndrome.
In general, glucose is used directly by tissues such as the muscles and brain as an energy source. Excess glucose is stored in the liver as glycogen (a glucose polymer) but can also be converted into fructose by the polyol biochemical pathway. By contrast, fructose is almost exclusively metabolized by the liver. In this organ, ketohexokinase (KHK) — a liver-specific fructose-metabolizing enzyme also known as fructokinase — traps fructose in liver cells as fructose 1-phosphate. Unlike fructose 6-phosphate (an isomer of fructose 1-phosphate that participates in the biochemical pathway of glycolysis), fructose 1-phosphate can bypass a major regulatory step in glycolysis that generates fructose 1,6-bisphosphate through the action of the energy-sensitive enzyme phosphofructokinase. Thus, fructose can be converted into fat, unfettered by the cellular controls that prevent unrestrained lipid synthesis from glucose.
By this logic, diets high in fructose could cause excess fat accumulation in the liver, leading to the liver disorders fatty liver disease, steatohepatitis and, ultimately, cirrhosis. Liver fat could also be released into the circulation and taken up by fat cells in other tissues, resulting in obesity. Furthermore, the circulating fat could accelerate the onset of cardiovascular disease, insulin resistance and type 2 diabetes. So fructose over-consumption may be at the heart of metabolic syndrome, which has also been linked to poor outcome of a wide range of cancers.(Nature 502, 181–182 (10 October 2013) doi:10.1038/502181a)