Dr.Soumitra Chakravarty MD
List the key enzymes of Galactose and Fructose metabolism
Differentiate the clinical features and the enzyme deficiency in
essential Fructosuria and hereditary fructose intolerance
Differentiate the clinical features and enzyme deficiency in non
classical and classical Galactosemia
Briefly describe lactose intolerance and its clinical manifestations
Describe the pathogenesis of Diabetes Mellitus and its
complications.
SYNTHESIZES URONIC ACID
URONIC ACID IS REQUIRED FOR :A. Synthesis of GAGs  Synthesis of Glycoproteins and
Proteoglycans
B. Conjugation of Bilirubin and Drugs
Fructose enters glycolysis either as fructose 6-po4 or fructose 1-po4.
Phosphorylation by Hexokinase or fructokinase
Fructokinase found in liver, kidney and small intestine
Hexokinase in skeletal muscle and most organs
Features of Fructose metabolism
Entry of fructose into the cells is – not dependent on
insulin.
Phosphorylation to fructose -1- phosphate by enzyme
fructokinase in liver.
1. Is not dependent on amount of fructose in plasma
2. Is not dependent on insulin.
In extra hepatic tissues: glucose competes with fructose
for hexokinase.
Fructose metabolism
Muscle which contains only
hexokinase  phosphorylates
fructose to F6P which is a direct
glycolytic intermediate.
Hepatic fructose is
phosphorylated on C-1 by
fructokinase yielding fructose-1phosphate.
Enzyme
Hexokinase
Glucokinase
Fructokinase
Substrate
All Hexoses
Glucose
Fructose
Location
All tissues
Liver
Liver
Affinity
High affinity
(Glucose> Fructose)
Low affinity
High affinity for FRUCTOSE
Velocity of reaction
Slow
Fast
Fast
Phosphorylation
POSITION
6-PO4
6-PO4
1-PO4
Bypass rate limiting
step (PFK-1)
No
No
Yes
Regulation by insulin
Not regulated
Regulated
Not regulated
Uric
acid
SLOWER
FASTER
Aldolase A , B and C.
Aldolase B is present in liver,
kidney and small intestine
converts fructose 1-P into DHAP
and glyceraldehyde.
Aldolase A is a glycolytic
enzyme in all other tissues.
Aldolase C is present in
Brainsimilar to aldolase A
Kinetics of metabolism
Rate of fructose metabolism > rate of glycolysis since
fructokinase/Aldolase B bypasses PFK-1 – the rate
limiting step of glycolysis.
Elevated levels of dietary fructose 
increased rate of lipogenesis( fatty acid and triglyceride
synthesis) in liver as a result of Acetyl CoA and glycerol-3PO4 accumulation formed by the more rapid fructose
metabolism .
Remember – Sucrose contains glucose + fructose !!
PROVIDES ENERGY
SEMINAL PLASMA – ENERGY REQUIRED FOR
MOBILITY OF SPERMATOZOA
Secreted by Seminal Vesicle
Fructose
ATP
Fructokinase
Essential
Fructosuria
def
ADP
Fructose-1-Po4
Aldolase B
Glyceraldehyde
def
Hereditary Fructose
intolerance
Dihydroxyacetone
phosphate
Fructokinase deficiency:
Autosomal recessive – benign condition
Excretion of fructose in urine [ no other abnormality]
Wrong diagnosis of Diabetes mellitus
Treatment  Avoid fructose .
Hereditary Fructose intolerance
Deficiency of aldolase B
Accumulation of fructose-1- phosphate
Deficiency of phosphates in cells.
Liver failure
Hypoglycemia
Hyperuricemia
Liver failure – glycogen accumulation.
Hyperuricemia
Hypoglycemia
Inhibition of glycogen phosphorylase.
+
Depletion of ATP also hampers Gluconeogenesis
Hypoglycemia
Depletion of ATP.AMP rises and in absence of
inorganic Pi , AMP is destroyed
(because the end product of purine catabolism is Uric acid )
Acute ingestion – vomiting, nausea etc.
Prolonged fructose ingestion in infants leads to poor
feeding, vomiting, hepatomegaly, jaundice,
hemorrhage, proximal‐renal‐tubule syndrome
(fanconi like syndrome)
Note :- Don’t confuse facconi’s syndrome with
Fanconi’s anaemia !!
Aldose reductase –
lens, retina, kidney
cells, Schwann
cells, placenta,
cells of ovaries and
seminal vesicles.
Aldose reductase
Sorbitol dehydrogenase
No sorbitol
dehydrogenase
Compliations due to increased glucose:
Hyperglycemia (as in diabetes) results in elevated levels of
intracellular glucose in lens, nerve, kidney.
This leads to water retention in these tissues due to
osmotic effects of sorbitol swelling, cataract, peripheral
neuropathy and vascular problems  nephropathy and
retinopathy as complications of diabetes
Harpe29th ed
Functions of Galactose in Body
Energy Converted to Glucose
Synthesis of Lactose
Synthesis of Glycosaminoglycans Glycoproteins
and Proteoglycans
Harper 29th
Galactose
Glycogen
Glucose 1P
Galactose 1p
Glucose 1P
Glucose 6P
Glucose
Galactose
GALACTOKINASE
UDP Glc
Galactose 1 P
GALACTOSE 1 P URIDYL
TRANSFERASE
UDP Gal
Glucose 1 P
Glucose 6 P
Glucose
1. Galactokinase deficiency
2. Galactose 1-phosphate
uridyl transferase
deficiency
3. UDP-galactose 4
epimerase deficiency.
UDP -Galactose
UDP-galactose is required for biosynthesis of:
Lactose
Glycoproteins
Glycosaminoglycans
Glycolipids
Non Classical Galactosemia
Deficiency of enzyme Galactokinase
Autosomal recessive
Less severe compared to classic type.
Early onset of cataract in first few months of life.
Classical Galactosemia
Galactose 1-phosphate uridyltransferase deficiency
(GALT) deficiency
Galactosemia, Galactosuria, vomiting, Diarrhoea,
jaundice, cataract formation
Liver damage- cirrhosis and brain damage - mental
retardation
Accumulation would inhibit the production of the
second messenger inositol in the signalling system and
hence causing a mental retardation.
Lippincott’s
Galactitol
Liver Damage and Cirrhosis due to
accumulation of Gal-1P
Gal-1P gets deposited in Renal
tubules
A newborn vomits after each feeding of milk based formula and does not
gain weight. Biochemical testing reveals a severe def of Galactose-1phosphate uridyl transferase. If this condition goes untreated, which of the
following is the likely outcome for this patient?
A.
B.
C.
D.
E.
Benign disease except for cataract formation
Chronic emphysema appearing in early adulthood
Chronic renal failure appearing in adolescence
Mental retardation and later death in infancy
Gastrointestinal symptoms that remit with puberty
A 4-month-old infant is brought to emergency clinic by the parents in an
unconscious state. The mother complains that the child has had repeated
attacks of unconsciousness, especially in the night, in the past few months. On
examination, the child had massive Hepatomegaly. Biochemical tests revealed
that the blood glucose level was 40mg/dL. The lactate and triglyceride and uric
acid levels in circulation were increased. Urine did not contain any reducing
sugar. The developmental milestones of the child were normal; however, the
weight gain of the infant was poor. Administration of glucagon failed to increase
the blood glucose level. What is the most probable biochemical defect?
Von Gierke disease
Classical Galactosemia
Hereditary fructose intolerance
Essential Fructosuria
Medium chain acyl Co-A dehydrogenase deficiency