Diets high in sucrose or in high-fructose syrups (HFCS 42 and HFCS55) used in manufactured foods and beverages lead to large amounts of fructose (and glucose) entering the hepatic portal vein. Note that high fructose corn syrup despite the name does not have much more fructose than sucrose (50% fructose). In fact, other dietary sources of sugar have more fructose (eg, apples 73%). The important issue is the total quantity of simple sugars ingested is too high. In 1900 Americans ingested about 15 g/day of fructose (50 kcal/day) primarily from fruits and vegetables, in 2020 it is 77 g/day and in children it is about 81 g/day (~300 kcals/day), a sixfold increase. The American Heart Association recommended keeping the intake below 25 g/day (100 kcal/day) for women and children and 37 g/day (150 kcal/day) for men, as the risk of obesity, hyperuriacidemia, high blood pressure, and diabetes are increased when simple sugar intake is high.

Nearly 90% of the dietary fructose is metabolized by the liver. Fructose undergoes more rapid glycolysis in the liver than does glucose because it bypasses the regulatory step catalyzed by phosphofructokinase (Figure 1). This allows fructose to flood the pathways in the liver, leading to increased fatty acid synthesis, esterification of fatty acids, and secretion of very-low-density lipoprotein (VLDL), which may raise serum triacylglycerols and ultimately raise LDL cholesterol concentrations. Fructokinase in liver, kidney, and intestine catalyzes the phosphorylation of fructose to fructose-1 phosphate. This enzyme does not act on glucose, and, unlike glucokinase, its activity is not affected by fasting or by insulin, which may explain why fructose is cleared from the blood of diabetic patients at a normal rate. Fructose-1-phosphate is cleaved to d-glyceraldehyde and dihydroxyacetone phosphate byaldolase B, an enzyme found in the liver, which also functions in glycolysis in the liver by cleaving fructose 1,6-bisphosphate. d-Glyceraldehyde enters glycolysis via phosphorylation to glyceraldehyde-3 phosphate catalyzed by triokinase. The two triose phosphates, dihydroxyacetone phosphate and glyceraldehyde-3-phosphate, may either be degraded by glycolysis or may be substrates for aldolase and hence gluconeogenesis, which is the fate of much of the fructose metabolized in the liver. To amplify the carbo hydrate loading effect of fructose, fructose-1-phosphate activates glucokinase and thus amplifies dietary glucose entry into liver. In addition, because of the rapid entry and phosphorylation of fructose the consumption of ATP is very fast causing a rise in ADP and AMP. AMP can be converted to hypoxanthine in the liver and to uric acid (xanthine oxidase) that can cause gout.

Fig1. Metabolism of fructose. Aldolase A is found in all tissues, whereas aldolase B is the predominant form in liver. (*Not found in liver.)

Extrahepatic tissues generally do not see much fructose. However in those tissues hexokinase catalyzes the phosphorylation of most hexose sugars, including fructose, but glucose inhibits the phosphorylation of fructose since it is a better substrate for hexokinase. Nevertheless, some fructose can be metabolized in adipose tissue and muscle. Fructose is found in seminal plasma and in the fetal circulation of ungulates and whales. Aldose reductase is found in the placenta of the ewe and is responsible for the secretion of sorbitol into the fetal blood. The presence of sorbitol dehydrogenase in the liver, including the fetal liver, is responsible for the conversion of sorbitol into fructose. This pathway is also responsible for the occurrence of fructose in seminal fluid.

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مواضيع ذات صلة

Galactose is Needed for the Synthesis of Lactose, Glycolipids, Proteoglycans, & Glycoproteins

Reactions of the Pentose Phosphate Pathway Occur in the Cytosol

Blood Glucose is Derived From the Diet, Gluconeogenesis, & Glycogenolysis

Glycolysis & gluconeogenesis share the same pathway but in opposite directions, & are reciprocally regulated

Glucose-1-Phosphate & Glycogen

Thermodynamic Barriers Prevent a Simple Reversal of Glycolysis

Gluconeogenesis & the Control of Blood Glucose: Biomedical Importance

Glycogen Metabolism is Regulated by A Balance in Activities Between Glycogen Synthase & Phosphorylase

cAMP Activates Glycogen Phosphorylase

Cyclic AMP Integrates The Regulation of Glycogenolysis & Glycogenesis

Glycogenolysis is not the Reverse of Glycogenesis, it is A Separate Pathway

Glycogenesis Occurs Mainly in Muscle & Liver