Essential Fructosuria to Galactose Metabolism Pathway & Summary

Essential Fructosuria

Involves a defect in fructokinase. Autosomal recessive. A benign, asymptomatic condition (fructokinase deficiency is kinder), since fructose is not trapped in cells. Hexokinase becomes 1° pathway for converting fructose to fructose-6-phosphate. Symptoms: fructose appears in blood and urine. Disorders of fructose metabolism cause milder symptoms than analogous disorders of galactose metabolism.

Hereditary Fructose Intolerance

Hereditary deficiency of aldolase B. Autosomal recessive. Fructose-1-phosphate accumulates, causing a ↓ in available phosphate, which results in inhibition of glycogenolysis and gluconeogenesis. Symptoms present following consumption of fruit, juice, or honey. Urine dipstick will be ⊝ (tests for glucose only); reducing sugar can be detected in the urine (nonspecific test for inborn errors of carbohydrate metabolism). Symptoms: hypoglycemia, jaundice, cirrhosis, vomiting. Treatment: ↓ intake of fructose, sucrose (glucose + fructose), and sorbitol (metabolized to fructose).

Fructose Metabolism Pathway

#boundingbox

This diagram illustrates the normal fructose metabolism pathway and highlights the enzymes involved. Fructose is converted to Fructose-1-P by Fructokinase. Fructose-1-P is then cleaved by Aldolase B into Dihydroxyacetone-P and Glyceraldehyde. Glyceraldehyde can be converted to Glyceraldehyde-3-P by Triose kinase, eventually feeding into Glycolysis. Dihydroxyacetone-P can also enter Glycolysis or be converted to Glycerol via NADH.

Galactokinase deficiency

Hereditary deficiency of galactokinase. Galactitol accumulates if galactose is present in diet. Relatively mild condition. Autosomal recessive. Symptoms: galactose appears in blood (galactosemia) and urine (galactosuria); infantile cataracts. May present as failure to track objects or to develop a social smile. Galactokinase deficiency is kinder (benign condition).

Classic Galactosemia

Absence of galactose-1-phosphate uridyltransferase. Autosomal recessive. Damage is caused by accumulation of toxic substances (including galactitol, which accumulates in the lens of the eye). Symptoms develop when infant begins feeding (lactose present in breast milk and routine formula) and include failure to thrive, jaundice, hepatomegaly, infantile cataracts, intellectual disability. Can predispose to E coli sepsis in neonates. Treatment: exclude galactose and lactose (galactose + glucose) from diet.

Galactose Metabolism Pathway and Key Defects

#boundingbox

This diagram shows the galactose metabolism pathway. Galactose is converted to Galactose-1-P by Galactokinase, then to Glucose-1-P by Uridyltransferase. UDP-Gal and UDP-Glu are interconverted by 4-Epimerase, feeding into Glycolysis/glycogenesis. An alternative pathway converts Galactose to Galactitol via Aldose reductase.

Remember this mnemonic: Fructose is to Aldolase B as Galactose is to UridylTransferase (FAB GUT). The more serious defects lead to PO43- depletion.

Topics Covered:

• Essential Fructosuria
• Hereditary Fructose Intolerance
• Fructose Metabolism Pathway
• Galactokinase Deficiency
• Classic Galactosemia
• Galactose Metabolism Pathway & Summary