Fructose Metabolism Fructose can enter glycolysis and gluconeogenesis. Glucose is a main metabolic...
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Transcript of Fructose Metabolism Fructose can enter glycolysis and gluconeogenesis. Glucose is a main metabolic...
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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 >> 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
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17-19
after dietary fructose consumption
low blood glucose level
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Excess fructose is toxic.
•Accumulation of fructose 1-P causes damage to liver. fructosekinase > aldolase B in activity
•Metabolism of (fructose by fructokinase) >> (glucokinase for glucose) in liverGenerated fructose 1-P stimulates pyruvate kinase.
Hypertriglyceridemia
improper substitute of glucose for diabete patient
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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 phosphorylasestimulates 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 + ATPADP + Pi + “energy provided by electron transport chain” ATPNet: Pi + fructose fructose 1-PThe ATP levels fall precipitously inside cells.Cells cannot perform normal work functions.
•Deficiency of fructose 1,6-bisphophatase causes similar effect.
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Galactose metabolism
Galactose can enter glycolysis and gluconeogenesis
Phosphorylation of galactose by galactokinase: Galactose 1-PUDP-galactose is an epimer of UDP-glucoserecyclereversible: internal sources for other biosynthesis
Galactosemia
Deficiency of galactose 1-P uridyl transferaseAccumulation of galactose (cataract) or galactose 1-P (damage to liver)
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17-20
Recycle
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17-23Polyol pathway
Galactose Galactitol no reaction
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Other pathways
Pentose phosphate pathway
Produces ribose 5-P and NADPHOxidative branch: irreversible, high [NADPH]/[NADP+] NADPH is a stronger reductant than NADH in cells.
Non-oxidative branch: irreversible
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17-21
Oxidative branch of pentose phosphate pathway
3 glucose 6-P + 6 NADP+
2 fructose 6-P + glyceraldehyde 3-P+ 6 NADPH + 6H + + 3 CO2
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17-22Non-oxidative branch of pentose phosphate pathway
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Thiamine pyrophosphate
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17-21
Oxidative branch of pentose P pathway
3 glucose 6-P + 6 NADP+
2 fructose 6-P + glyceraldehyde 3-P+ 6 NADPH + 6H + + 3 CO2
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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 NADPHGenerating ribose 5-P from oxidative branch, reverse reaction in Non-oxidative branchUsed in muscle , where glucose 6-P dehydrogenase level is low and nucleotides are stored.
2. Need both ribose 5-P and NADPHPredominantly oxidative branch and phosphate pentose isomerase reaction.
3. need NADPH more than ribose 5-PGenerating fructose 5-P and glyceraldehyde 3-P by both branchesChanged to glucose 6-P through gluconeogenesisThus, 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 glutathioneMany 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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Glu
Gly
Cys
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Box 17-1,2,3
-Glu Cys SH + Gly
-Glu SH Cys Gly
-Glu Cys S Gly
-Glu S Cys Gly
-Glu 2 Cys SH + Gly
H2O2
-Glu Cys S Gly
-Glu S Cys + 2 H2O Gly
-Glu 2 Cys SH + Gly
NADP+
-Glu Cys S Gly
-Glu S Cys + NADPH + H+
Gly
Glutathione
peroxidase
Glutathione
reductase
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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 ( 표 17-3 참고 )
•Essential pentosuria
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17-24
Synthesis of amino sugars
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17-25
essential pentosuria
Uronic acid pathway
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