After monosaccharides like fructose and galactose are absorbed in the intestine, the body needs to convert these sugars into glucose. This is necessary for further use of glucose in metabolic reactions (such as glycolysis or gluconeogenesis). A deficiency of enzymes responsible for these processes leads to the accumulation of fructose and galactose in the blood, causing diseases like galactosemia and fructosemia.
The goal of converting monosaccharides into glucose is to create a single universal substrate for metabolic reactions, specifically α-D-glucose. This allows the body to save resources and not synthesize multiple enzymes for each monosaccharide. The conversion process mainly occurs in the liver and the intestinal epithelium.
Mnemonic for remembering:
"Liver and intestine — convert to glucose quickly and reliably." 🧠
Conversion of Galactose to GlucoseGalactose phosphorylation:Galactose is phosphorylated on its first carbon, forming galactose-1-phosphate.
An important step: The conversion to glucose occurs through the synthesis of UDP-galactose from galactose-1-phosphate.
UDP-glucose is used for the synthesis of UDP-galactose, which is already present in the cell.
Isomerization of UDP-galactose:UDP-galactose isomerizes into UDP-glucose.
From there, it can:
- Participate in the transfer of UDP to galactose-1-phosphate.
- Be converted into free glucose and enter the bloodstream.
- Go on to synthesize glycogen.
Biochemical Complexity:The conversion of galactose to glucose is more complex due to the synthesis of UDP-galactose, which plays a role in the mammary gland during lactose formation.
Galactose is also used to synthesize hexosamines, which are part of heteropolysaccharides.
Galactose Metabolism DisordersGenetic enzyme defects:Galactose metabolism disorders are associated with defects in one of the enzymes:
- Galactokinase (defect frequency 1:500,000).
- Galactose-1-phosphate uridyltransferase (1:40,000).
- Epimerase (less than 1:1,000,000).
Galactosemia:These defects result in the disease called galactosemia.
Diagnosis:Children may refuse to eat, and the galactose concentration in the blood increases to 11.1–16.6 mmol/L (normal is 0.3–0.5 mmol/L), with galactose-1-phosphate present in the blood.
Pathogenesis:Excess galactose is converted into galactitol (dulcitol), which osmotically draws water into the lens, leading to cataracts.
Due to energy deficiency from the enzyme defect, the activity of many enzymes is disrupted, resulting in cell damage (neurons, hepatocytes, nephrocytes).
Treatment:Exclusion of milk and galactose-containing foods from the diet.
Early diagnosis and treatment, no later than 2 months after birth.
Mnemonic for remembering galactosemia:"Galactose — if not removed, cataracts and mental retardation." 👁️
Conversion of Fructose to GlucoseFructose Activation:Fructose can be activated by phosphorylation either on the 6th carbon to form fructose-6-phosphate (catalyzed by hexokinase) or on the 1st carbon to form fructose-1-phosphate (catalyzed by fructokinase).
Hexokinase has a low affinity for fructose, so this pathway is weak in the liver.
Fructose-1-phosphate:Upon activation of fructose by fructokinase, fructose-1-phosphate is formed, which is then converted into glyceraldehyde and dihydroxyacetone phosphate.
These compounds participate in either glycolysis or are converted into fructose-6-phosphate, which further converts into glucose.
Muscle Metabolism of Fructose:In muscles, fructose is directly converted into fructose-6-phosphate because fructokinase is absent in muscles.
This pathway leads to the inclusion of fructose in glycolysis or glycogen synthesis.
Insulin-Independent Fructokinase:Fructokinase is insulin-independent, allowing fructose to rapidly convert into pyruvate and acetyl-CoA. This can lead to excess fatty acid and triacylglycerol production.
Fructose Metabolism DisordersEssential Fructosuria:This is a benign condition caused by a fructokinase deficiency. It is asymptomatic and requires no treatment.
Hereditary Fructosuria:This condition is caused by defects in other fructose metabolism enzymes (e.g., fructose-1-phosphate aldolase). It manifests after fruits and juices are introduced into an infant's diet.
Pathogenesis:Enzyme deficiency leads to impaired glycogen mobilization and decreased gluconeogenesis, resulting in hypoglycemia and lethargy.
Diagnosis:Diagnosis involves tests for hypophosphatemia, hyperuricemia, hypoglycemia, and fructosuria. Confirmation is done with a fructose tolerance test.
Treatment:A diet restricting fruits, sweet foods, and vegetables.
Mnemonic for remembering fructosuria:"Fructose on the rise — an egoistic disease." 🍎