Metabolism of Fructose

Source sucrose fruits, honey and vegetables

Metabolism
Fructose is metabolized by the liver.
1.Phosphorylation of fructose to F 1P by
fructokinase
2.F1P is split into glyceraldehyde and
dihdoxyacetone PO4
3.Glyceraldehyde is phosphorylated to
Glyceraldehyde 3P that enters the glycolysis.
 Rate of fructose metabolism is more rapid than
glucose.
Increase dietary intake of fructose elevated the
rate of lipogenesis.
Loading of liver with fructose potentiate
hypertriglyceridemia, hypercholesterolemia &
hyperuricemia.
 Defects in Fructose metabolism
Diet Fructose Fructokinase F-1P

Aldolase B
Fructosemia
Glyceraldehyde 3P
Hereditary Fructose intolerance
 Defects in Fructose metabolism
Hepatic fructokinase deficiency- Essential
fructosuria
Absence of aldolase B Hereditary fructose
intolerance
Fructose & sorbitol in lens- associated with Diabetic
cataract
Sorbitol (polyol) pathway (not found in liver) is
resposible for fructose formation from glucose &
increases in activity as glucose conc: rises in those
tissues that are not insulin sensitive ie. Lens,
peripheral nerves & renal glomeruli.
 Glucose is reduced to sorbitol by aldose reductase &
oxidized by sorbitol dehydrogenase. Sorbitol does not
diffuse through cell membranes, but accumulates
causing osmotic damage.
Aldose Reductase
Glucose Sorbitol
NAD+
NADPH+ H+ NADP+
Sorbitol
dehydrogenase
NADH + H+

Fructose
 Galactose metabolism
Source lactose milk.
Entry of galactose into the cells is insulin independent.

Metabolism
1.Galactose is phosphorylated to Gal 1P by
galactokinase.
2.Gal 1P reacts with UDP Glu to form UDP-Gal and Glu
1P by Gal 1P uridyl transferase
3.Epimerization of UDP Gal to UDP Glu by epimerase
4.Glu 1P to Glu 6P by isomerase
Galactose Galactokinase Gal 1P UDP-Glc

Galaltose 1P Galactosemia
uridyl transferase

G1P UDP-Gal
 Metabolic significance
- Galactose is required for glycolipids, proteoglycans
and glycoproteins
Enzyme deficiencies in galactose pathway cause
Galactosemia ie. Galactokinase, uridyl transferase or
epimerase
Commonest- uridyl transferase deficiency
 Alcohol metabolism
Alcohol is metabolized in liver, first converted to
acetaldehyde by alcohol dehydrogenase, then to
acetate by aldehyde dehydrogenase.
It causes accumulation of acetaldehyde in blood,
results in flushing, tachycardia , hyperventilation &
nausea.
From above 2 reactions there is massive increase
cytosolic NADH
Abundence of NADH favors reduction of pyruvate to
lactate & oxaloacetate to malate both are
intermediates of gluconeogenesis.
 Ethanol Alcohol dehrogenase Acetaldehyde
NAD+
NAD+ NADH
Aldehyde
dehrogenase
NADH
Acetate
Lactate dehrogenase
Pyruvate Lactate

Glucose NADH NAD+

 This can precipitate hypoglycemia, particularly
in persons who have depleted liver glycogen
stores.
Thus alcohol consumption in individuals those
fasted or in prolonged strenuous exercise can
produce hypoglycemia
 Learning outcome
Metabolic defect of fructose & galactose metabolism.
Alcohol metabolism & hypoglycemia