nill

1. • We need to remember that galactose is a
metabolite of lactose
• Lactose is broken down to one molecule of
glucose and galactose
GALACTOSE METABOLISM

2. • There are no catabolic pathways to metabolize
galactose, so the strategy is to convert
galactose into a metabolite of glucose
• The first reaction in the galactose–glucose
interconversion pathway is the
phosphorylation of galactose to galactose 1-
phosphate by galactokinase in the liver

3. • Galactose 1-phosphate then acquires a uridyl
group from uridine diphosphate glucose (UDP-
glucose)

4. • The products of this reaction, which is catalyzed
by galactose 1-phosphate uridyl transferase, are
UDP-galactose and glucose 1-phosphate
• The galactose moiety of UDP-galactose is then
epimerized to glucose.
• The configuration of the hydroxyl group at carbon
4 is inverted by UDP-galactose 4-epimerase
• Note that UDP-glucose is not consumed in the
conversion of galactose into glucose, because it is
regenerated from UDP-galactose by the
epimerase
• Finally, glucose 1-phosphate, formed from
galactose, is isomerized to glucose 6-phosphate
by phosphoglucomutase

5. Lactase deficiency
• Causes a condition known as Lactose intolerance, or hypolactasia
• Lactose is fermented in the colon to lactic acid, methane and
hydrogen gas
• The gas produced creates the uncomfortable feeling of gut
distention and the annoying problem of flatulence(bloating)
• Lactic acid and lactose are osmotically active, they draw water into
the intestines which leads to diarrhea, dehydration
• Diagnosis is based on a positive hydrogen breath test after an oral
lactose load.
• Best treatment is to avoid foods containing lactose, milk and milk
products (except unpasteurized yogurt, which contains active
Lactobacillus) or by lactase pills.

6. Galactosemia
• important enzymes in galactose metabolism
are:
• Galactokinase
• Galactose 1-phosphate uridyltransferase
• The disruption of galactose metabolism is
referred to as galactosemia
• The most common form is called clasic
galactosemia which is an inherited deficiency
of Galactose 1-phosphate uridyltransferase

7. • symptoms manifest on day three of life and
affected infants fail to thrive
• Vomiting and diarrhea occur after milk
ingestion, liver cirrhosis, jaundice which does
not resolve on phototherapy, severe bacterial
infections, Failure to thrive, lethargy,
hypotonia, and mental retardation are other
common and apparent features
• Babies will also develop cataracts

8. mgt
• mandatory screening of newborns for
galactosemia is recommended through a
newborn heel prick test in the early weeks of
life
• formulas containing galactose-free
carbohydrates are given
• The life expectancy will then be normal with
an appropriate diet.

9. cataracts
• A cataract is the clouding of the normally clear
lens of the eye
• The eye lens has high concentrations of aldose
reductase enzyme.
• In absence of galactose metabolizing enzymes,
aldose reductase reduces galactose to
galactitol

10. • Galactitol is osmotically active leading to
osmotic damage of the lens

11. FRUCTOSE METABOLISM

12. • Fructose is found in honey and fruit and as part
of the disaccharide sucrose (common table sugar)
• Sucrose is hydrolyzed by intestinal brush border
sucrase, and the resulting monosaccharides,
glucose and fructose, are absorbed into the
portal blood
• The liver phosphorylates fructose and cleaves it
into glyceraldehyde and DHAP
• The important enzymes are,
– Fructokinase
– Fructose 1-P aldolase (aldolase B)

13. • Genetic deficiency of fructokinase is benign and
often detected incidentally when the urine is
checked for glucose with a dipstick
• Fructose 1-phosphate aldolase deficiency is a
severe disease because of accumulation of
fructose 1-phosphate in the liver and renal
proximal tubules
• Symptoms are reversed after removing fructose
and sucrose from the diet
• Are cataracts part of the complications?

14. Hereditary Fructose Intolerance
• Hereditary fructose intolerance is an autosomal
recessive disease (incidence of 1/20,000) due to a
defect in the gene that encodes aldolase B in
fructose metabolism
• There is accumulation of fructose 1-phosphate in
hepatocytes and thereby sequestering of
inorganic phosphate in this substance
• Eventually, the liver becomes damaged due to the
accumulation of trapped fructose 1-phosphate
• Signs include lethargy, jaundice, vomiting,
diarrhoea