Fructose 1-phosphate

Fructose 1-phosphate (F1P) is a fructose sugar phosphorylated on carbon 1. It plays a crucial role in the metabolism of fructose taken up by the liver, primarily from dietary sources. The metabolism of fructose to fructose 1-phosphate is a key step in the fructolysis pathway, which is distinct from glycolysis, the metabolic pathway for glucose.

Biochemistry

Fructose is metabolized by the liver using the fructolysis pathway. The first step in this process involves the enzyme fructokinase, which catalyzes the phosphorylation of fructose to fructose 1-phosphate. This reaction consumes one molecule of ATP (adenosine triphosphate), converting it to ADP (adenosine diphosphate). Unlike the phosphorylation of glucose to glucose-6-phosphate in glycolysis, which is regulated by insulin, the phosphorylation of fructose to fructose 1-phosphate is not regulated by hormones and proceeds at a rapid rate in the liver.

Physiological Role

Fructose 1-phosphate serves as a substrate for aldolase B, an enzyme that splits it into dihydroxyacetone phosphate (DHAP) and glyceraldehyde. Both of these products can enter the glycolytic pathway, leading to the production of pyruvate and ultimately ATP, NADH, and other metabolic intermediates. The rapid metabolism of fructose 1-phosphate in the liver can lead to a depletion of ATP and an accumulation of lactic acid, contributing to the potential for metabolic syndrome and fatty liver disease when fructose is consumed in large amounts.

Clinical Significance

A deficiency in aldolase B, which is required for the metabolism of fructose 1-phosphate, leads to hereditary fructose intolerance (HFI). Individuals with HFI cannot properly metabolize fructose 1-phosphate, leading to its accumulation in the liver. This accumulation can cause severe hypoglycemia, liver damage, and kidney failure. Avoidance of dietary fructose, sucrose, and sorbitol is the primary treatment for individuals with HFI.

Metabolic Disorders

Excessive intake of fructose has been linked to various metabolic disorders, including obesity, type 2 diabetes, and non-alcoholic fatty liver disease (NAFLD). The rapid metabolism of fructose to fructose 1-phosphate in the liver is thought to play a role in these conditions by promoting de novo lipogenesis, uric acid formation, and insulin resistance.

See Also

• Fructose metabolism
• Fructokinase
• Aldolase B
• Hereditary fructose intolerance
• Metabolic syndrome
• Non-alcoholic fatty liver disease