Fructose Metabolism

Overview – Fructose Metabolism

•  Source
  • sucrose in fruits and sweeteners
    • disaccharide of glucose and fructose
    • hydrolyzed by sucrase in brush border of small intestine
• Pathway
  • liver is main site of metabolism
    • also in renal proximal tubule
  • DHAP and glyceraldehyde enter into glycolysis downstream of regulation
• Clinical relevance
  • fructokinase deficiency 
    • benign
    • presentation
      • fructosuria 
      • does not have the osmotic pathologies (e.g. cataracts) associated with galactokinase deficiencies
        • fructose is not an aldose and therefore not substrate for aldose reductase
  • fructose 1-P aldolase (aldolase B) deficiency
    • aka hereditary fructose intolerance 
    • AR
    • more severe than fructokinase deficiency because fructose 1-P acts as a phosphate sink
    • presentation
      • fructosuria
      • lethargy
      • hypoglycemia
      • liver and proximal renal tubule disorder
        • hyperbilirubinemia
        • hyperuricemia
          • degradation of ADP due to loss of P_i
    • treatment
• fructose (and sucrose)-free diet

Fructose Metabolism – Introduction

Fructose is a simple sugar or monosaccharide that is naturally found in many fruits, vegetables, and honey. It is also commonly used as a sweetener in processed foods and beverages, often in the form of high-fructose corn syrup (HFCS).

When we consume fructose, it is broken down and metabolized in the liver, where it can be used for energy or stored as glycogen for later use. However, unlike glucose, which can be metabolized by every cell in the body, fructose can only be metabolized by the liver.

Types

There are two main types of fructose metabolism in the body:

1. Hepatic fructose metabolism: The majority of fructose metabolism occurs in the liver, where fructose is transported into the liver cells via the fructose transporter GLUT5. Inside the liver, fructose is converted to fructose-1-phosphate by the enzyme fructokinase. Fructose-1-phosphate is then cleaved by the enzyme aldolase B into dihydroxyacetone phosphate (DHAP) and glyceraldehyde. DHAP can be converted into glycerol-3-phosphate, which can be used to synthesize triglycerides, while glyceraldehyde can be converted into glucose or lactate.
2. Extrahepatic fructose metabolism: In addition to the liver, some fructose can be metabolized in other tissues, such as adipose tissue, muscle, and the small intestine. In these tissues, fructose is transported into the cells via the glucose transporter GLUT2. Once inside the cell, fructose is also metabolized by fructokinase to produce fructose-1-phosphate, which is then converted into DHAP and glyceraldehyde.

Studies

Here are some recent studies on fructose metabolism:

1. A 2020 study published in the journal Nutrients examined the effects of fructose on liver metabolism in rats. The study found that high levels of fructose intake led to an increase in liver fat accumulation and inflammation, which could contribute to the development of non-alcoholic fatty liver disease.
2. A 2019 study published in the journal Advances in Nutrition analyzed the impact of fructose consumption on metabolic health in humans. The study concluded that high fructose consumption can lead to adverse metabolic effects, such as insulin resistance, dyslipidemia, and obesity.
3. A 2018 study published in the Journal of Lipid Research investigated the molecular mechanisms underlying fructose metabolism in the liver. The study found that fructose is metabolized differently than glucose and can lead to the formation of harmful metabolites that contribute to the development of liver disease.
4. A 2017 study published in the Journal of the Academy of Nutrition and Dietetics analyzed the relationship between fructose consumption and cardiovascular disease risk factors in children and adolescents. The study found that higher fructose intake was associated with increased levels of triglycerides, a type of fat that can contribute to heart disease.
5. A 2016 study published in the American Journal of Clinical Nutrition investigated the effects of high-fructose corn syrup (HFCS) on insulin resistance and inflammation in humans. The study found that consuming high levels of HFCS led to an increase in insulin resistance and inflammation markers, which could contribute to the development of type 2 diabetes.

Overall, these studies suggest that consuming high levels of fructose, particularly in the form of added sugars, can have negative health effects on metabolism and may contribute to the development of various chronic diseases.

Function

Fructose metabolism refers to the process by which the body breaks down and utilizes fructose, a type of simple sugar that is found in fruits, honey, and some vegetables. Fructose metabolism is primarily carried out in the liver and involves a series of biochemical reactions.

Here are some key functions of fructose metabolism:

1. Energy production: One of the primary functions of fructose metabolism is to generate energy for the body. Fructose is broken down into glucose, which is then used by cells to produce ATP, the main source of energy for cellular processes.
2. Glycogen synthesis: Fructose can also be converted into glycogen, a stored form of glucose that the body can use as an energy source when blood sugar levels are low. Glycogen is primarily stored in the liver and muscles.
3. Lipid synthesis: Fructose can also be used to synthesize lipids, including triglycerides, which are stored in adipose tissue as a source of energy.
4. Regulation of appetite and satiety: Fructose metabolism can influence the release of hormones that regulate appetite and satiety. For example, fructose can stimulate the release of insulin and leptin, which signal the brain to reduce food intake.
5. Oxidative stress: High levels of fructose metabolism can lead to the production of reactive oxygen species (ROS), which can cause oxidative stress and damage to cells and tissues. This can contribute to the development of various chronic diseases.

Complications

1. Insulin Resistance: Fructose has been linked to insulin resistance, a condition in which cells do not respond well to insulin, a hormone that regulates blood sugar levels. This can lead to elevated blood sugar levels, which can increase the risk of developing type 2 diabetes.
2. Fatty Liver Disease: Excessive fructose intake can also lead to the accumulation of fat in the liver, a condition known as nonalcoholic fatty liver disease (NAFLD). NAFLD is a common condition that can progress to more serious liver problems, such as cirrhosis.
3. Obesity: Fructose is a source of empty calories, meaning it provides energy but no nutritional value. Consuming too much fructose can contribute to weight gain and obesity.
4. Metabolic Syndrome: Metabolic syndrome is a cluster of conditions that increase the risk of heart disease, stroke, and diabetes. It is characterized by abdominal obesity, high blood pressure, elevated blood sugar levels, and abnormal lipid levels. High fructose intake has been linked to an increased risk of metabolic syndrome.
5. Dental Caries: Fructose is a sugar that can contribute to the development of dental caries (cavities) when consumed in excess.
6. Gout: High fructose intake can increase uric acid levels in the blood, which can lead to gout, a form of arthritis characterized by joint pain and swelling.

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