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Introduction

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High-Yield Terms

  • High-fructose corn syrup (HFCS): refers to the sugar syrup generated from corn starch by enzymatic conversion of a portion of the glucose to fructose. Commonly contains 55% fructose and identified as HFCS-55

  • HFCS and sucrose: represent the 2 primary sources of fructose in the human diet

  • GLUT5 and GLUT2: intestinal sugar transporters responsible for fructose uptake and then delivery to the blood, respectively

  • Ketohexokinase: two isoforms KHK-A and KHK-C catalyze phosphorylation of fructose to fructose 1-phosphate, also called frucktokinase

  • Aldolase B: enzyme catalyzing hydrolysis of fructose 1-phosphate to glyceraldehyde and dihydroxyacetone phosphate (DHAP)

  • Fructose-induced feeding: metabolism of fructose within the brain results in suppression of anorexigenic signals while activating orexigenic signals

  • Hereditary fructose intolerance: potentially fatal infant disorder resulting from defect in the level of aldolase B activity

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Dietary Fructose

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Diets containing large amounts of sucrose (a disaccharide of glucose and fructose) can utilize the fructose as a major source of energy. The amount of fructose available from sucrose obtained from cane or beet sugars is not significantly less than that from corn syrup. Corn syrup is somewhat improperly identified as high-fructose corn syrup (HFCS), giving the impression that it contains a large amount of fructose. However, whereas the fructose content of sucrose is 50% (since it is a pure disaccharide of only glucose and fructose), the content in HFCS is only 55% (referred to as HFCS-55). The reason HFCS has more than 50% fructose is because the glucose extracted from corn starch is treated with glucose isomerase to convert most of the glucose to fructose yielding HFCS-90. The HFCS-90 is then mixed with glucose syrup to produce either HFCS-55 or HFCS-42, both of which are used in food preparations. Therefore, any disorder and/or dysfunction, attributed to the consumption of fructose, can be manifest whether one consumes cane or beet sugar or HFCS.

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Following ingestion of sucrose or HFCS, it is degraded in the gut through the action of sucrose-isomaltase into its constituent monosaccharides, glucose, and fructose. As indicated in Chapter 7, glucose is absorbed from the lumen of the intestine via the action of SGLT1 and fructose is absorbed via GLUT5. Once in the intestinal enterocyte, the glucose and fructose can enter the blood via GLUT2-mediated transport. Fructose in the blood does not stimulate insulin secretion from the pancreas and its cellular uptake is insulin-independent.

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Activation of Fructose

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The pathway to utilization of fructose differs in muscle and liver due to the differential distribution of fructose-phosphorylating enzymes. Hexokinases are a family of enzymes that phosphorylate hexose sugars such as glucose and fructose. Four mammalian isozymes of hexokinase are known (Types I–IV), with the Type IV isozyme often referred to as glucokinase. Glucokinase is the form of the enzyme found in hepatocytes and pancreatic β-cells. In addition to hexokinases, fructose can be phosphorylated by fructokinases.

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Although both KHK-C and ...

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