Ketohexokinase

Ketohexokinase (KHK), also known as fructokinase, is an enzyme that catalyzes the phosphorylation of fructose to form fructose 1-phosphate, an important step in the metabolism of fructose. This enzyme plays a crucial role in the fructose metabolism pathway, which is significant for energy production in the body. The activity of ketohexokinase is particularly high in the liver, kidney, and intestine, where fructose metabolism primarily occurs.

Function

Ketohexokinase catalyzes the first step in the metabolic pathway of fructose, converting fructose to fructose 1-phosphate. This reaction is essential for the utilization of fructose obtained from the diet. The enzyme uses ATP as a phosphate donor and is highly specific for fructose as a substrate. The product, fructose 1-phosphate, is then further metabolized to produce energy or to synthesize glycogen and lipids.

Genetics

The gene encoding ketohexokinase, KHK, is located on the human chromosome. There are two isoforms of the enzyme, KHK-A and KHK-C, which are produced through alternative splicing of the KHK gene. The KHK-C isoform is the catalytically active form involved in fructose metabolism, while the KHK-A isoform has a lower affinity for fructose and is less active.

Clinical Significance

Abnormalities in fructose metabolism, due to mutations in the KHK gene or excessive intake of fructose, can lead to various metabolic disorders. One such condition is hereditary fructose intolerance (HFI), where the absence or reduced activity of aldolase B (an enzyme downstream of KHK in the fructose metabolism pathway) leads to the accumulation of fructose 1-phosphate, causing toxic effects.

Excessive consumption of fructose, often found in sugar-sweetened beverages and processed foods, can overload the fructose metabolism pathway, leading to increased synthesis of triglycerides and uric acid. This can contribute to the development of metabolic syndrome, non-alcoholic fatty liver disease (NAFLD), and gout.

Research Directions

Research on ketohexokinase has focused on understanding its role in fructose metabolism and its implications for health. Studies have explored the potential of targeting KHK as a therapeutic approach for metabolic disorders associated with high fructose consumption. Inhibitors of ketohexokinase are being investigated for their ability to reduce the metabolic effects of excessive fructose intake.

See Also

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