Fruktoz Metabolizmas?

1

• Fructose Metabolism
• Fructose can enter glycolysis and
  gluconeogenesis.
• Glucose is a main metabolic fuel in most
  organisms.
• Other sugars convert to glycolytic intermediates.
• Fructose metabolism is faster than glucose in
  blood.
• Hexokinase can phosphorylate fructose
• Fructose ATP ? Fructose 6-P ADP
• Km for fructose gtgt Km for glucose, thus important
  only if frucose is high.
• Most of fructose metabolized to fructose 1-P by
  fructokinase.
• Fructose ATP ? Fructose 6-P ADP
• Adolase B cleaves the molecule of fructose into
  two 3-Carbon compounds.
• dihydroxyaceton-P glycealdehyde
  glycogenesis/gluconeogenesis

2
after dietary fructose consumption
low blood glucose level
17-19
3

• Excess fructose is toxic.
• Accumulation of fructose 1-P causes damage to
  liver.
• fructosekinase gt aldolase B in activity
• Metabolism of (fructose by fructokinase) gtgt
  (glucokinase for glucose) in liver
• Generated fructose 1-P stimulates pyruvate
  kinase.
• Hypertriglyceridemia
• ? improper substitute of glucose for diabete
  patient

4

• Disorder of fructose metabolism
• Essential fructosuria deficiency of fructokinase
• Hereditary fructose intolerance deficiency of
  aldolase B
• -Accumulation of fructose 1-P
• inhibits aldolase, phosphohexose isomerase and
  glycogen phosphorylase
• stimulates glucokinase
• -Tying up Pi in the form of fructose 1-P makes it
  impossible for liver mitochondria to generate ATP
  by oxidative phosphorylation.
• fructose ATP ? fructose 1-P ATP
• ADP Pi energy provided by electron transport
  chain ? ATP
• Net Pi fructose ? fructose 1-P
• The ATP levels fall precipitously inside cells.
• Cells cannot perform normal work functions.
• Deficiency of fructose 1,6-bisphophatase causes
  similar effect.

5
Galactose metabolism Galactose can enter
glycolysis and gluconeogenesis Phosphorylation
of galactose by galactokinase Galactose
1-P UDP-galactose is an epimer of
UDP-glucose recycle reversible internal sources
for other biosynthesis Galactosemia Deficiency
of galactose 1-P uridyl transferase Accumulation
of galactose (cataract) or galactose 1-P (damage
to liver)
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Recycle
17-20
7
Galactose Galactitol no
reaction
17-23
Polyol pathway
8
Other pathways Pentose phosphate
pathway Produces ribose 5-P and NADPH Oxidative
branch irreversible, high NADPH/NADP NADPH
is a stronger reductant than NADH in
cells. Non-oxidative branch irreversible
9
3 glucose 6-P 6 NADP 2 fructose 6-P
glyceraldehyde 3-P 6 NADPH 6H 3 CO2
Oxidative branch of pentose phosphate pathway
17-21
10
17-22
Non-oxidative branch of pentose phosphate pathway
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Thiamine pyrophosphate
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3 glucose 6-P 6 NADP 2 fructose 6-P
glyceraldehyde 3-P 6 NADPH 6H 3 CO2
Oxidative branch of pentose P pathway
17-21
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Use of oxidative and nonoxidative branches is
dependent on need of NADPH and ribose 5-P in
cells 1. When cells need ribose 5-P more than
NADPH Generating ribose 5-P from oxidative
branch, reverse reaction in Non-oxidative
branch Used in muscle , where glucose 6-P
dehydrogenase level is low and nucleotides are
stored. 2. Need both ribose 5-P and
NADPH Predominantly oxidative branch and
phosphate pentose isomerase reaction. 3. need
NADPH more than ribose 5-P Generating fructose
5-P and glyceraldehyde 3-P by both
branches Changed to glucose 6-P through
gluconeogenesis Thus, theoretically all glucose
can be converted to CO2 and NADPH.
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• Activity of pentose phosphate pathway
• The cell keeps the ratio of NADPH/NADP at
  above 100 to favor reductive biosynthesis.
• In some tissues such as adrenal cortex, lactating
  mammary gland and liver, where fatty acid and
  cholesterol synthesis are rapid, as much as 30
  of glucose is metabolized by the pentose
  phosphate shunt. (weak in brain and muscle)
• NADPH as an antioxidant important to tissues
  exposed to high oxygen pressure such as the
  cornea
• Oxidative branch produces NADPH, The first step
  in oxidative branch is oxidation of glucose 6-P
  via glucose 6-P dehydrogenase

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• Deficiency of glucose 6-P causes hemolytic
  anemia.
• The pentose phosphate pathway supplies the RBC
  with NADPH to maintain the reduced state of
  glutathione.
• -Oxidation of glucose 6-P via glucose 6-P
  dehydrogenase to produce NADPH.
• The inability to maintain reduced glutathione in
  RBCs leads to increased accumulation of
  peroxides, predominantly H2O2, that in turn
  results in a weakening of the cell wall and
  concomitant hemolysis.
• The pentose phosphate pathway in erythrocytes is
  essentially the only pathway for these cells to
  produce NADPH. Any defect in the production of
  NADPH could, therefore, have profound effects on
  erythrocyte survival.
• Oxidant drugs increase the oxidation of
  glutathione
• Many anti-malarial drugs, etc.
• Plasmodium requires the reducing power of NADPH
  for their life cycle.
• Favism
• Viral hepatitis, pneumonia, and typhoid fever

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a
b
Glu
g
Cys
a
a
Gly
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g-Glu ? Cys ?SH ? Gly
g-Glu ? SH ? Cys
? Gly
g-Glu ? Cys ?S ? ? Gly
g-Glu ? S ? Cys
? Gly
g-Glu ? 2 Cys ?SH ? Gly
g-Glu ? Cys ?S ? ? Gly
g-Glu ? S ? Cys 2
H2O ? Gly
H2O2
Glutathione peroxidase
g-Glu ? 2 Cys ?SH ? Gly
g-Glu ? Cys ?S ? ? Gly
g-Glu ? S ? Cys NADPH
H ? Gly
NADP
Glutathione reductase
Box 17-1,2,3
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• Fructose is a major sugar in semen
• Advantage over bacteria
• Polyol pathway is present in the seminal vesicles
  for fructose synthesis for seminal fluid (energy
  source for spermatozoa)
• Amino sugar synthesis from glucose (? 17-3 ??)
• Essential pentosuria

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Synthesis of amino sugars
17-24
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essential pentosuria
Uronic acid pathway
17-25
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