The intake of added sugars, such as from table sugar (sucrose) and high-fructose corn syrup has increased dramatically in the last hundred years and correlates closely with the rise in obesity, metabolic syndrome, and diabetes. Fructose is a major component of added sugars and is distinct from other sugars in its ability to cause intracellular ATP depletion, nucleotide turnover, and the generation of uric acid. In this article, we revisit the hypothesis that it is this unique aspect of fructose metabolism that accounts for why fructose intake increases the risk for metabolic syndrome. Recent studies show that fructose-induced uric acid generation causes mitochondrial oxidative stress that stimulates fat accumulation independent of excessive caloric intake. These studies challenge the long-standing dogma that “a calorie is just a calorie” and suggest that the metabolic effects of food may matter as much as its energy content. The discovery that fructose-mediated generation of uric acid may have a causal role in diabetes and obesity provides new insights into pathogenesis and therapies for this important disease.

https://diabetes.diabetesjournals.org/content/diabetes/62/10/3307.full.pdf

Sugar, Uric Acid, and the Etiology of Diabetes and Obesity

Fructose and sugar: A major mediator of non-alcoholic fatty liver disease

https://dspace.ewha.ac.kr/bitstream/2015.oak/223203/1/001.pdf

Uric Acid Induces Hepatic Steatosis by Generation of Mitochondrial Oxidative Stress POTENTIAL ROLE IN FRUCTOSE-DEPENDENT AND -INDEPENDENT FATTY LIVER

Increased sugar consumption is increasingly considered to be a contributor to the worldwide epidemics of obesity and diabetes and their associated cardiometabolic risks. As a result of its unique metabolic properties, the fructose component of sugar may be particularly harmful. Diets high in fructose can rapidly produce all of the key features of the metabolic syndrome. Here we review the biology of fructose metabolism as well as potential mechanisms by which excessive fructose consumption may contribute to cardiometabolic disease.

/pdf/fructose-metabolism-and-metabolic-disease-d9hfguwizm.pdf

Fructose metabolism and metabolic disease

Uric acid and cardiovascular disease.

1. The hepatic concentration of several nucleotides and metabolites was measured during the first few minutes after an intravenous load of fructose to mice. The first changes, observed at 30s, were a decrease in the concentration of Pi and a simultaneous accumulation of fructose 1-phosphate. The decrease in the concentrations of ATP and GTP proceeded more slowly. An increase in the concentration of IMP was detected only after 1 min and could therefore not be considered to be the cause of the accumulation of fructose 1-phosphate. 2. To explain the temporary burst of adenine nucleotide breakdown that occurs after a load of fructose, the kinetics of AMP deaminase (EC 3.5.4.6) from rat liver were reinvestigated at physiological (0.2 mM) concentration of substrate. For this purpose, a new radiochemical-assay procedure was developed. At 0.2mM-AMP a low activity could be measured, which was more than 90% inhibited by 5mM-Pi. ATP (3MM) increased the enzyme activity over 200-fold. Pi alone did not influence the ATP-activated enzyme, but 0.5mM-GTP caused a 60% inhibition. The combined effect of both inhibitors at their physiological concentrations reached 95%. 3. It is proposed that the rapid degradation of adenine nucleotides that occurs after a load of fructose is caused by a decrease in the concentration of both inhibitors, Pi and GTP, soon counteracted by the decrease in the concentration of ATP. 4. Some of the kinetic parameters of liver AMP deaminase were computed in terms of the concerted transition theory of Monod, Wyman & Changeux (1965) (J. Mol. Biol. 12, 88-118).

/pdf/the-mechanism-of-adenosine-triphosphate-depletion-in-the-5666lsfqkp.pdf

R Vanneste

Papers

The mechanism of adenosine triphosphate depletion in the liver after a load of fructose. A kinetic study of liver adenylate deaminase