16.3 Fructose and Galactose Metabolism

Fructose and galactose, two important monosaccharides, have unique metabolic pathways that differ from glucose. Their metabolism involves specific enzymes and intermediates, allowing for efficient energy production and utilization in the body.

Understanding these pathways is crucial, as disorders in fructose or galactose metabolism can lead to serious health issues. Excessive fructose intake and genetic conditions affecting these pathways highlight the importance of balanced sugar consumption in our diets.

Fructose Metabolism

Enzymatic Conversion of Fructose

• Fructokinase catalyzes the phosphorylation of fructose to fructose-1-phosphate using ATP as a phosphate donor
• Fructokinase functions primarily in the liver, small intestine, and kidney
• Aldolase B cleaves fructose-1-phosphate into dihydroxyacetone phosphate and glyceraldehyde
  • Dihydroxyacetone phosphate enters glycolysis directly
  • Glyceraldehyde requires phosphorylation by triokinase before entering glycolysis
• Fructose-1-phosphate acts as an intermediate in fructose metabolism
  • Accumulates when fructose intake exceeds the capacity of aldolase B
  • Can inhibit glycogenolysis and gluconeogenesis

Metabolic Significance and Disorders

• Fructose metabolism bypasses the rate-limiting step of glycolysis (phosphofructokinase)
  • Allows for rapid conversion of fructose to triglycerides
• Excessive fructose consumption can lead to increased lipogenesis and insulin resistance
• Hereditary fructose intolerance results from a deficiency in aldolase B
  • Characterized by symptoms such as vomiting, hypoglycemia, and liver damage upon fructose ingestion
  • Diagnosed through genetic testing or liver biopsy
  • Managed through strict dietary fructose restriction (fruits, table sugar)

Galactose Metabolism

Leloir Pathway: Enzymatic Steps

• Galactokinase initiates galactose metabolism by phosphorylating galactose to galactose-1-phosphate
  • Requires ATP as a phosphate donor
• Galactose-1-phosphate uridylyltransferase catalyzes the transfer of UDP from UDP-glucose to galactose-1-phosphate
  • Produces UDP-galactose and glucose-1-phosphate
• UDP-galactose 4-epimerase converts UDP-galactose to UDP-glucose
  • Completes the conversion of galactose to glucose
• Leloir pathway represents the primary route for galactose metabolism in humans
  • Named after Luis Federico Leloir, who elucidated the pathway

Metabolic Significance and Disorders

• Galactose serves as a component of lactose, the primary sugar in milk
• Galactose metabolism is crucial for proper utilization of dietary lactose
• Galactosemia results from deficiencies in enzymes of the Leloir pathway
  • Classic galactosemia: deficiency in galactose-1-phosphate uridylyltransferase
  • Galactokinase deficiency: leads to cataracts but milder symptoms overall
  • UDP-galactose 4-epimerase deficiency: rarest form with varying severity
• Symptoms of galactosemia include failure to thrive, liver damage, and cataracts
• Management of galactosemia involves strict dietary restriction of galactose and lactose (dairy products)