From the Guidelines
Fructose metabolism integrates with glucose metabolism through the shared glycolytic intermediate dihydroxyacetone phosphate (DHAP), allowing for rapid metabolism and potential metabolic issues with excessive consumption. When fructose enters cells, it is phosphorylated by fructokinase to form fructose-1-phosphate, which is then cleaved by aldolase B into DHAP and glyceraldehyde 1. DHAP directly enters the glycolytic pathway, which is the same pathway used in glucose metabolism. Meanwhile, glyceraldehyde is phosphorylated to glyceraldehyde-3-phosphate, another glycolytic intermediate. This metabolic convergence allows fructose to bypass the rate-limiting phosphofructokinase step of glycolysis, enabling rapid metabolism even when glucose metabolism is regulated or inhibited.
The shared pathway explains why fructose can be quickly converted to fat in the liver and why excessive fructose consumption can lead to metabolic issues like non-alcoholic fatty liver disease and insulin resistance 1. According to the most recent evidence, fructose consumed as “free fructose” (i.e., naturally occurring in foods such as fruit) may result in better glycemic control compared with isocaloric intake of sucrose or starch, and free fructose is not likely to have detrimental effects on triglycerides as long as intake is not excessive (.12% energy) 1.
Some key points to consider:
- Fructose can be quickly converted to fat in the liver, leading to potential metabolic issues with excessive consumption 1
- The shared glycolytic pathway allows fructose to bypass regulatory controls, enabling rapid metabolism 1
- Free fructose consumption may result in better glycemic control compared to sucrose or starch, but excessive intake should be avoided 1
- People with diabetes should limit or avoid intake of sugar-sweetened beverages (SSBs) to reduce risk for weight gain and worsening of cardiometabolic risk profile 1
From the Research
Shared Glycolytic Intermediate
The integration of fructose metabolism with glucose metabolism can be explained by the shared glycolytic intermediate, fructose-1,6-bisphosphate. This intermediate is formed from the phosphorylation of fructose by fructokinase and aldolase, and is then converted to glyceraldehyde-3-phosphate and dihydroxyacetone phosphate by the enzyme fructose-1,6-bisphosphate aldolase 2, 3.
Role of Fructose-1,6-Bisphosphate Aldolase
Fructose-1,6-bisphosphate aldolase is a key enzyme in the glycolytic pathway, catalyzing the reversible cleavage of fructose-1,6-bisphosphate to glyceraldehyde-3-phosphate and dihydroxyacetone phosphate. The structure of this enzyme has been studied, and the catalytic mechanism has been elucidated 2, 3. The enzyme uses a Schiff base-forming mechanism, where the substrate fructose-1,6-bisphosphate is covalently bound to the enzyme, allowing for the cleavage of the C-C bond.
Integration with Glucose Metabolism
The shared glycolytic intermediate, fructose-1,6-bisphosphate, allows for the integration of fructose metabolism with glucose metabolism. Glucose is converted to glucose-6-phosphate, which is then converted to fructose-6-phosphate, and finally to fructose-1,6-bisphosphate by the enzyme phosphofructokinase. This intermediate can then be converted to glyceraldehyde-3-phosphate and dihydroxyacetone phosphate by the enzyme fructose-1,6-bisphosphate aldolase, allowing for the entry of fructose into the glycolytic pathway 4, 5.
Key Findings
- Fructose-1,6-bisphosphate is a shared glycolytic intermediate that allows for the integration of fructose metabolism with glucose metabolism 2, 3.
- Fructose-1,6-bisphosphate aldolase is a key enzyme in the glycolytic pathway, catalyzing the reversible cleavage of fructose-1,6-bisphosphate to glyceraldehyde-3-phosphate and dihydroxyacetone phosphate 2, 3.
- The structure of fructose-1,6-bisphosphate aldolase has been studied, and the catalytic mechanism has been elucidated 2, 3.
- The integration of fructose metabolism with glucose metabolism allows for the efficient assimilation of dietary glucose and fructose by the liver 5.
Metabolic Pathways
- Glycolysis: the metabolic pathway that converts glucose to pyruvate, with fructose-1,6-bisphosphate as a key intermediate 4, 5.
- Pentose phosphate pathway: a metabolic pathway that generates NADPH and pentoses from glucose-6-phosphate, with fructose-1,6-bisphosphate as a key intermediate 5.
- De novo lipogenesis: a metabolic pathway that generates fatty acids from glucose and fructose, with fructose-1,6-bisphosphate as a key intermediate 5.