Inborn Errors of Fructose Metabolism. What Can We Learn from Them?

Christel Tran

doi:10.3390/nu9040356

Abstract

Fructose is one of the main sweetening agents in the human diet and its ingestion is increasing globally. Dietary sugar has particular effects on those whose capacity to metabolize fructose is limited. If intolerance to carbohydrates is a frequent finding in children, inborn errors of carbohydrate metabolism are rare conditions. Three inborn errors are known in the pathway of fructose metabolism; (1) essential or benign fructosuria due to fructokinase deficiency; (2) hereditary fructose intolerance; and (3) fructose-1,6-bisphosphatase deficiency. In this review the focus is set on the description of the clinical symptoms and biochemical anomalies in the three inborn errors of metabolism. The potential toxic effects of fructose in healthy humans also are discussed. Studies conducted in patients with inborn errors of fructose metabolism helped to understand fructose metabolism and its potential toxicity in healthy human. Influence of fructose on the glycolytic pathway and on purine catabolism is the cause of hypoglycemia, lactic acidosis and hyperuricemia. The discovery that fructose-mediated generation of uric acid may have a causal role in diabetes and obesity provided new understandings into pathogenesis for these frequent diseases.

Highlights

People in developed countries may ingest up to 50 to 100 g fructose equivalents daily in their diet and the use of this sugar in foods and drinks is increasing globally [1,2]
Three inborn errors are known in the pathway of fructose metabolism; (1) essential or benign fructosuria due to fructokinase deficiency; (2) hereditary fructose intolerance (HFI); and (3) fructose-1,6-bisphosphatase (FBPase) deficiency
Studies conducted in patients with inborn errors of fructose metabolism helped to understand fructose metabolism and its potential toxicity

Summary

Introduction

People in developed countries may ingest up to 50 to 100 g fructose equivalents daily in their diet and the use of this sugar in foods and drinks is increasing globally [1,2]. Fructose is almost exclusively derived from the diet. It is found in its free form in honey, fruits, and many vegetables, and is associated with glucose in the disaccharide sucrose in numerous foods and beverages. Widely distributed in fruits and vegetables, is converted to fructose in the liver by sorbitol dehydrogenase. Exogenous fructose is absorbed through glucose transport proteins (GLUT) 5 and 2 across the intestinal epithelium and is metabolized (mainly in the liver) by the enzymes fructokinase, aldolase B, and triokinase. Three inborn errors are known in the pathway of fructose metabolism; (1) essential or benign fructosuria due to fructokinase deficiency; (2) hereditary fructose intolerance (HFI); and (3) fructose-1,6-bisphosphatase (FBPase) deficiency. The potential toxic effects of fructose in healthy humans are discussed: it is essential to understand these toxic effects in order to comprehend the pathophysiology of HFI and of FBPase deficiency

Enzyme of Fructose

Fructose

Inborn Errors of Fructose Metabolism: A Model for Fructose Toxicity

Findings

Conclusions