The major source of fructose is sucrose, which, when cleaved, releases equimolar amounts of fructose and glucose.
The major source of
fructose is sucrose, which, when cleaved, releases equimolar amounts of
fructose and glucose (Figure 12.8). Transport of fructose into cells is insulin
independent. Fructose is first phosphorylated to fructose 1-phosphate by
fructokinase and then cleaved by aldolase B to dihydroxyacetone phosphate and
glyceraldehyde. These enzymes are found in the liver, kidney, and small
intestinal mucosa. A deficiency of fructokinase causes a benign condition
(essential fructosuria), but a deficiency of aldolase B causes hereditary
fructose intolerance (HFI), in which severe hypoglycemia and liver failure lead
to death if fructose (and sucrose) in the diet is not eliminated. Mannose, an
important component of glycoproteins, is phosphorylated by hexokinase to
mannose 6-phosphate, which is reversibly isomerized to fructose 6-phosphate by
phosphomannose isomerase. Glucose can be reduced to sorbitol (glucitol) by
aldose reductase in many tissues, including the lens, retina, Schwann cells,
liver, kidney, ovaries, and seminal vesicles. In cells of the liver, ovaries,
and seminal vesicles, a second enzyme, sorbitol dehydrogenase, can oxidize
sorbitol to produce fructose. Hyperglycemia results in the accumulation of
sorbitol in those cells lacking sorbitol dehydrogenase. The resulting osmotic
events cause cell swelling and may contribute to the cataract formation,
peripheral neuropathy, nephropathy, and retinopathy seen in diabetes. The major
dietary source of galactose is lactose. The transport of galactose into cells
is not insulin dependent. Galactose is first phosphorylated by galactokinase (a
deficiency results in cataracts) to galactose 1-phosphate. This compound is
converted to uridine diphosphate (UDP)-galactose by galactose 1-phosphate
uridyltransferase (GALT), with the nucleotide supplied by UDP-glucose. A
deficiency of this enzyme causes classic galactosemia. Galactose 1-phosphate
accumulates, and excess galactose is converted to galactitol by aldose
reductase. This causes liver damage, severe intellectual disability, and
cataracts. Treatment requires removal of galactose (and lactose) from the diet.
For UDP-galactose to enter the mainstream of glucose metabolism, it must first
be converted to UDP-glucose by UDP-hexose 4-epimerase. This enzyme can also be
used to produce UDP-galactose from UDP-glucose when the former is required for
the synthesis of structural carbohydrates. Lactose is a disaccharide that
consists of galactose and glucose. Milk and other dairy products are the
dietary sources of lactose. Lactose is synthesized by lactose synthase from
UDP-galactose and glucose in the lactating mammary gland. The enzyme has two
subunits, protein A (which is a galactosyltransferase found in most cells where
it synthesizes N-acetyllactosamine) and protein B (α-lactalbumin, which is
found only in the lactating mammary glands, and whose synthesis is stimulated
by the peptide hormone prolactin). When both subunits are present, the
transferase produces lactose.
Figure 12.8 Key concept map
for metabolism of fructose and galactose. GALT = galactose 1-phosphate
uridylyltransferase; UDP = uridine diphosphate; P = phosphate.
12.1 A nursing female with classic galactosemia is
on a galactose-free diet. She is able to produce lactose in breast milk
because:
A. galactose can be
produced from fructose by isomerization.
B. galactose can be produced from a glucose
metabolite by epimerization.
C. hexokinase can
efficiently phosphorylate galactose to galactose 1-phosphate.
D. the enzyme affected
in galactosemia is activated by a hormone produced in the mammary gland.
Correct answer = B. Uridine diphosphate (UDP)-glucose
is converted to UDP-galactose by UDP-hexose 4-epimerase, thereby providing the
appropriate form of galactose for lactose synthesis. Isomerization of fructose
to galactose does not occur in the human body. Galactose is not converted to
galactose 1-phosphate by hexokinase. A galactose-free diet provides no
galactose. Galactosemia is the result of an enzyme deficiency.
12.2 A 5-month-old boy is brought to his physician
because of vomiting, night sweats, and tremors. History revealed that these
symptoms began after fruit juices were introduced to his diet as he was being
weaned off breast milk. The physical examination was remarkable for
hepatomegaly. Tests on the baby’s urine were positive for reducing sugar but
negative for glucose. The infant most likely suffers from a deficiency of:
A. aldolase B.
B. fructokinase.
C. galactokinase.
D. β-galactosidase.
Correct answer = A. The symptoms suggest hereditary
fructose intolerance, a deficiency in aldolase B. Deficiencies in fructokinase or
galactokinase result in relatively benign conditions characterized by elevated
levels of fructose or galactose in the blood and urine. Deficiency in
β-galactosidase (lactase) results in a decreased ability to degrade lactose
(milk sugar). Congenital lactase deficiency is quite rare and would have
presented much earlier in this baby (and with different symptoms). Typical
lactase deficiency (adult hypolactasia) presents at a later age.
12.3 Lactose synthesis is essential in the
production of milk by mammary glands. In lactose synthesis:
A. galactose from
galactose 1-phosphate is transferred to glucose by galactosyltransferase
(protein A), generating lactose.
B. protein A is used
exclusively in the synthesis of lactose.
C. α-lactalbumin
(protein B) regulates the specificity of protein A by increasing its Km for
glucose.
D. protein B expression is stimulated by prolactin.
Correct answer = D. The expression of α-lactalbumin
(protein B) is increased by the hormone prolactin. Uridine
diphosphate–galactose is the form used by the galactosyltransferase (protein
A). Protein A is also involved in the synthesis of the amino sugar,
N-acetyllactosamine. Protein B increases the affinity of protein A for glucose
and, so, decreases the Km.
12.4 A 3-month-old girl is developing cataracts.
Other than not having a social smile or being able to track objects visually,
all other aspects of the girl’s examination are normal. Tests on the baby’s
urine are positive for reducing sugar but negative for glucose. Which enzyme is
most likely deficient in this girl?
A. Aldolase B
B. Fructokinase
C. Galactokinase
D. Galactose
1-phosphate uridylyltransferase
Correct answer = C. The girl is deficient in
galactokinase and is unable to appropriately phosphorylate galactose. Galactose
accumulates in the blood (and urine). In the lens of the eye, galactose is
reduced by aldose reductase to galactitol, a sugar alcohol, which causes
osmotic effects that result in cataract formation. Deficiency of galactose 1-phosphate
uridylyltransferase also results in cataracts but is characterized by liver
damage and neurologic effects. Fructokinase deficiency is a benign condition.
Aldolase B deficiency is severe, with affects on several tissues. Cataracts are
not typically seen.
Related Topics
TH 2019 - 2024 pharmacy180.com; Developed by Therithal info.