The hepatic metabolism of fructose, also known as fructolysis, has important effects on both glucose and lipid metabolism. Although metabolism of fructose through fructolysis uses many of the same enzymes as the metabolism of glucose through glycolysis, the two sugars have very different metabolic fates in human metabolism.
Unlike glucose, which is metabolized widely in the body, fructose is metabolized almost completely in the liver, where it is directed toward replenishment of liver glycogen and triglyceride synthesis. Absorbed fructose is delivered to the liver via the portal vein.
When fructose is present in excess of glucose, it is not very well absorbed and has been shown to cause osmotic diarrha. Unlike glucose, fructose is not an insulin secretagogue.
Fructose is also not metabolized in insulin-sensitive peripheral tissues. Fructose is selectively taken up and almost completely metabolized by liver hepatocytes. Very little fructose escapes the liver, and fructose is not metabolized to any great extent in the small intestine, which lacks the fructose phosphorylating enzyme fructokinase.
According to the lead author, of new University of Illinois study, Manabu Nakamura, dietary fructose affects a wide range of genes in the liver that had not previously been identified.
His study shows that the metabolism of fructose is more complex than the data had indicated. “Our gene-expression analysis showed that both insulin-responsive and insulin-repressive genes are induced during this process. Our bodies can do this, but it’s complicated, and we may pay a price for it,” he said.
In the study, 24 rats were fed either a 63 percent glucose or fructose diet four hours a day for two weeks; at the end of this period, half the animals fasted for 24 hours before the scientists performed a gene expression analysis; the other half were examined at the end of a four-hour feeding.
Fructose feeding not only induced a broader range of genes than had previously been identified, there were simultaneous increases in glycogen (stored glucose) and triglycerides in the liver.
“To our surprise, a key regulatory enzyme involved in the breakdown of glucose was about two times higher in the fructose-fed group than in the glucose-fed group,” Nakamura said.
The study also suggests that a protein called carbohydrate response element binding protein is responsible for the fructose effect on certain genes that trigger the production of fat, he said.
“We’re continuing to assess the risk of fructose insulin resistance and the consequent risk for development of diabetes,” he said. The study was published in a recent issue of Biochimica et Biophysica Acta.Tags:
- how are enzymes involved in the breakdown of fructose
- fructose metabolism
- Enzymes in Fructose Metabolism