20: Fructose Metabolism & Associated Disorders | Carbohydrates Metabolism | Biochemistry

Summary

In this video, Dr. Trupti delves into fructose metabolism, explaining how the body processes fructose differently in muscle, adipose tissue, liver, kidney, and intestines. The video also explores the myths surrounding fructose consumption in diabetes and highlights the harmful effects of excessive fructose intake, such as hyperlipidemia, fatty liver, and hyperuricemia. Dr. Trupti discusses key enzymes like fructokinase and aldolase B and their role in disorders such as hereditary fructose intolerance. With a detailed case study, she demonstrates the clinical implications of these metabolic disturbances and stresses the importance of managing fructose consumption in certain health conditions.

Takeaways

• 😀 Fructose is a monosaccharide and keto sugar found in foods like sucrose, honey, and fruits, which are the richest sources of fructose.
• 😀 Unlike glucose, fructose enters cells independently of insulin, and its metabolism varies between tissues, such as muscle, adipose tissue, liver, kidney, and intestine.
• 😀 In muscle and extrahepatic tissues, fructose is converted into fructose 6-phosphate, which can enter glycolysis, glycogenesis, or gluconeogenesis, depending on the body's metabolic state.
• 😀 In the liver, kidney, and intestine, fructose is converted into fructose 1-phosphate by the enzyme fructokinase, which is a key step in its metabolism.
• 😀 The metabolism of fructose in the liver leads to the formation of intermediates like glyceraldehyde and dihydroxyacetone phosphate, which can enter glycolysis or gluconeogenesis.
• 😀 Fructose metabolism bypasses the rate-limiting enzyme phosphofructokinase in glycolysis, leading to faster metabolism compared to glucose.
• 😀 Uncontrolled fructose metabolism, especially in excess, can lead to conditions like hyperlipidemia, fatty liver, and hyperuricemia due to the increased production of pyruvate and acetyl-CoA.
• 😀 Excess fructose consumption can cause decreased ATP levels and increased AMP degradation, which raises uric acid and contributes to hyperuricemia and lactic acidosis.
• 😀 The myth that fructose is harmless in diabetes is debunked—fructose consumption can be as harmful as glucose, contributing to fatty liver, hyperlipidemia, and increased cardiovascular risk.
• 😀 Hereditary fructose intolerance (HFI) is caused by a deficiency of the enzyme aldolase B, leading to the accumulation of fructose 1-phosphate and a range of symptoms, including hypoglycemia, vomiting, and jaundice.
• 😀 Essential fructose urea, a benign condition caused by a lack of fructokinase, results in fructose excretion in urine but does not cause severe health issues like HFI.

Q & A

What is the key difference between how fructose is metabolized in muscle tissues versus liver, kidney, and intestine?

In muscle and extrahepatic tissues, fructose is rapidly converted into fructose-6-phosphate by the action of hexokinase, which then enters glycolysis or glycogenesis. In liver, kidney, and intestine, fructose is converted into fructose-1-phosphate by fructokinase and then processed into dihydroxyacetone phosphate and glyceraldehyde-3-phosphate, entering glycolysis or gluconeogenesis.

Why is the metabolism of fructose faster than glucose metabolism?

Fructose metabolism is faster than glucose metabolism because it bypasses the rate-limiting step of glycolysis, which is catalyzed by phosphofructokinase. Instead, fructose is rapidly metabolized through aldolase B, leading to faster production of intermediates like glyceraldehyde-3-phosphate.

What role does aldolase B play in fructose metabolism?

Aldolase B is an enzyme crucial for breaking down fructose-1-phosphate into dihydroxyacetone phosphate and glyceraldehyde, both intermediates in the glycolysis pathway. It is specifically active in the liver, kidney, and intestine.

How does excess fructose consumption lead to hyperlipidemia and fatty liver?

Excess fructose intake increases the production of pyruvate, which is converted into acetyl-CoA. This acetyl-CoA is then used to synthesize free fatty acids, triacylglycerol, and cholesterol, contributing to hyperlipidemia and fatty liver.

Why is the belief that fructose is harmless in diabetes considered a myth?

Fructose is not harmless in diabetes because excessive fructose intake leads to increased fatty acid production, hyperlipidemia, fatty liver, hyperuricemia, and lactic acidosis, all of which worsen the condition in diabetic patients.

What is hereditary fructose intolerance and what enzyme deficiency causes it?

Hereditary fructose intolerance is an autosomal recessive disorder caused by a deficiency in aldolase B, which is responsible for converting fructose-1-phosphate into dihydroxyacetone phosphate and glyceraldehyde. This leads to the accumulation of fructose-1-phosphate and a range of health issues.

How does fructose intolerance lead to hypoglycemia?

In hereditary fructose intolerance, fructose-1-phosphate accumulates and inhibits glycogenolysis, gluconeogenesis, and glucose production, resulting in low blood glucose levels (hypoglycemia). This is further exacerbated by the inhibition of glucose-6-phosphate formation in the liver.

What are the clinical features of hereditary fructose intolerance?

The clinical features include hypoglycemia, nausea, vomiting, abdominal pain, jaundice, hepatomegaly, renal dysfunction, hyperuricemia, and lactic acidemia. These symptoms often appear when a child is weaned off milk and introduced to fructose or sucrose-rich foods.

What diagnostic tests are used to detect hereditary fructose intolerance?

Diagnosis can be made by detecting fructose in the urine using the Benedict's test and Seliwanoff's test. DNA-based testing can also confirm the diagnosis, particularly by identifying mutations in the aldolase B gene.

How is hereditary fructose intolerance treated?

Treatment involves the removal of fructose and sucrose from the diet to prevent the accumulation of fructose-1-phosphate and manage symptoms. Early detection and dietary management are crucial for preventing long-term complications.